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FTR #1132 This pro­gram was record­ed in one, 60-minute seg­ment. 

Intro­duc­tion: This broad­cast details the process of vet­ting the anti-Covid-19 drug remde­sivir, high­light­ing the insti­tu­tion­al short­cuts tak­en in test­ing the prod­uct, as well as the dubi­ous nature of the bil­lion­aires net­work­ing with offi­cials involved in the approval process.

Pre­vi­ous cov­er­age of remde­sivir has not­ed that:

1. The drug’s maker–Gilead Sciences–is a major hold­ing of hedge funds, Robert Mer­cer’s Renais­sance Tech­nolo­gies, in par­tic­u­lar.
2. Pos­i­tive data on the drug’s performance–however pre­lim­i­nary or incomplete–proved to be a dri­ver of mar­kets.
3. The Chair­man of the Board of Gilead for many years was Don­ald Rums­feld, who left to become George W. Bush’s Sec­re­tary of Defense.
4. A key, found­ing direc­tor of Gilead Sci­ences was C. Ben­no Schmidt. Schmidt was a dri­ving force behind the estab­lish­ment of Richard Nixon’s War on Can­cer, which served to cov­er for the devel­op­ment of AIDS.

Before ana­lyz­ing remde­sivir, how­ev­er, we update dis­cus­sion about the SARS CoV‑2 virus hav­ing been engi­neered, not­ing joint U.S.-Chinese projects in which bat-borne coro­n­avirus­es were genet­i­cal­ly engi­neered. The process­es used to mod­i­fy the virus­es would not show any overt evi­dence of human manip­u­la­tion.

Most impor­tant­ly, these projects received financ­ing from insti­tu­tions with doc­u­ment­ed links to U.S. intel­li­gence and mil­i­tary inter­ests.

Research into the his­to­ry of GOF (gain-of-func­tion) work on bat coro­n­avirus­es at the Wuhan Insti­tute of Virol­o­gy indi­cates mul­ti­ple areas of U.S. intel­li­gence pres­ence in that work. 

It was pub­licly dis­closed in a 2017 paper that the US and Chi­na col­lab­o­rat­ed on “gain-of-func­tion” research on bat coro­n­avirus­es to infect humans and that the work received fund­ing from the Unit­ed States Agency for Inter­na­tion­al Development–a fre­quent cut-out for the CIA.

In addi­tion, the work was also fund­ed in part by the Nation­al Insti­tutes of Health, which have col­lab­o­rat­ed with both CIA and the Pen­ta­gon in BSL‑4 (Bio-Safe­ty-Lev­el 4) projects. 

The Wuhan Insti­tute of Virol­o­gy has also part­nered with the USAMRIID since the mid-1980’s.

Impor­tant to note is the fact that it was pub­lic infor­ma­tion that some of this work was done in a biosafe­ty-lev­el 2 lab­o­ra­to­ry, giv­ing an observ­er intent on under­tak­ing a bio­log­i­cal war­fare covert oper­a­tion against Chi­na use­ful field intel­li­gence about the vul­ner­a­bil­i­ty of WIV for such an “op.”

1. The inves­ti­ga­tion of infec­tiv­i­ty used unde­tectable meth­ods, negat­ing arti­cles claim­ing the virus could not have been genet­i­cal­ly engi­neered: ” Evi­dence has emerged that researchers at the Wuhan Insti­tute of Virol­o­gy (WIV) in Chi­na, work­ing in col­lab­o­ra­tion with sci­en­tists in the USA, have been genet­i­cal­ly engi­neer­ing bat virus­es for the past sev­er­al years to inves­ti­gate infec­tiv­i­ty – using unde­tectable meth­ods. . . . The evi­dence rebuts claims by jour­nal­ists and some sci­en­tists that the SARS-CoV­‑2 virus respon­si­ble for the cur­rent COVID-19 pan­dem­ic could not have been genet­i­cal­ly engi­neered because it lacks the ‘signs’ or ‘sig­na­tures’ that sup­pos­ed­ly would be left behind by genet­ic engi­neer­ing tech­niques. . . .”
2. Dr. Richard Ebright not­ed that the research was joint­ly fund­ed by the U.S. and Chi­na, that Peter Daszak (about whom we have voiced reser­va­tions in the past) was one of the Amer­i­can col­lab­o­ra­tors. Fur­ther­more, the research was fund­ed in part by USAID, a com­mon U.S. intel­li­gence cut-out. ” . . . . Dr Richard Ebright, an infec­tious dis­ease expert at Rut­gers Uni­ver­si­ty (USA), has alert­ed the pub­lic to evi­dence that WIV and US-based researchers were genet­i­cal­ly engi­neer­ing bat virus­es to inves­ti­gate their abil­i­ty to infect humans, using com­mon­ly used meth­ods that leave no sign or sig­na­ture of human manip­u­la­tion. Ebright flagged up a sci­en­tif­ic paper pub­lished in 2017 by WIV sci­en­tists, includ­ing Shi Zhengli, the virol­o­gist lead­ing the research into bat coro­n­avirus­es, work­ing in col­lab­o­ra­tion with Peter Daszak of the US-based Eco­Health Alliance. Fund­ing was shared between Chi­nese and US insti­tu­tions, the lat­ter includ­ing the US Nation­al Insti­tutes of Health and USAID. The researchers report hav­ing con­duct­ed virus infec­tiv­i­ty exper­i­ments where genet­ic mate­r­i­al is com­bined from dif­fer­ent vari­eties of SARS-relat­ed coro­n­avirus­es to form nov­el ‘chimeric’ ver­sions. This formed part of their research into what muta­tions were need­ed to allow cer­tain bat coro­n­avirus­es to bind to the human ACE2 recep­tor – a key step in the human infec­tiv­i­ty of SARS-CoV­‑2. . . .”
3. Fur­ther­more, the researchers used a type of genet­ic engi­neer­ing that leaves no sig­na­ture of human manip­u­la­tion: ” . . . . The WIV sci­en­tists did this, Ebright points out, ‘using ‘seam­less lig­a­tion’ pro­ce­dures that leave no sig­na­tures of human manip­u­la­tion’. This is note­wor­thy because it is a type of genet­ic engi­neer­ing that Ander­sen and his team exclud­ed from their inves­ti­ga­tion into whether SARS-CoV­‑2 could have been engi­neered – and it was in use at the very lab that is the prime sus­pect for a lab escape. . . .”
4. In addi­tion, Ebright high­lights the 2015 work done by Ralph Bar­ic in col­lab­o­ra­tion with WIV’s Shi Zhengli–a project we have dis­cussed at length in the past: ” . . . . A group of sci­en­tists from the Uni­ver­si­ty of North Car­oli­na in the USA, with the WIV’s Shi Zhengli as a col­lab­o­ra­tor, pub­lished a study in 2015 describ­ing sim­i­lar exper­i­ments involv­ing chimeric coro­n­avirus­es, which were also cre­at­ed using stan­dard unde­tectable genet­ic engi­neer­ing tech­niques. . . .”
5. Ebright also cites work done in a bio-safe­ty lev­el 2 lab­o­ra­to­ry. : ” . . . . Ebright points out that the paper states, ‘All work with the infec­tious virus was per­formed under biosafe­ty lev­el 2 con­di­tions’. This lev­el is suit­able for work involv­ing agents of only ‘mod­er­ate poten­tial haz­ard to per­son­nel and the envi­ron­ment’. . . .But they are not at fault in fail­ing to use BSL‑4 for this work, as SARS coro­n­avirus­es are not aerosol-trans­mit­ted. The work does, how­ev­er, fall under biosafe­ty lev­el 3, which is for work involv­ing microbes that can cause seri­ous and poten­tial­ly lethal dis­ease via inhala­tion. . . .”
6. Dr. Jonathan Lath­am under­scored the reser­va­tions expressed by many con­cern­ing “gain-of-func­tion” exper­i­ments on these kinds of coro­n­avirus­es: ” . . . . The bio­sci­en­tist Dr Jonathan Lath­am crit­i­cised the kind of research on bat coro­n­avirus­es that has been tak­ing place in Wuhan and the USA as ‘pro­vid­ing an evo­lu­tion­ary oppor­tu­ni­ty’ for such virus­es ‘to jump into humans’. Lath­am, who has a doc­tor­ate in virol­o­gy, argues that this kind of work is sim­ply ‘pro­vid­ing oppor­tu­ni­ties for con­t­a­m­i­na­tion events and leak­ages from labs, which hap­pen on a rou­tine basis’. . . .”

Note, again, that the whole world was informed back in 2017 that  dan­ger­ous research involv­ing the cre­ation of bat coro­n­avirus­es to infect humans was being car­ried out in Chi­na.  Note again, that the research was fund­ed in part by the US, includ­ing USAID–a fre­quent U.S. intel­li­gence cut-out; the NIH–which has active­ly col­lab­o­rat­ed with both CIA and Pen­ta­gon. The WIV has also part­nered with the USAMRIID.

Flash for­ward a cou­ple of years and we have a night­mare virus that ini­tial­ly appeared to pop up near­by the WIV, with the Trump admin­is­tra­tion aggres­sive­ly push­ing the idea that it escaped from that lab.

In that con­text, we note the fol­low­ing:

1. In 2017, Chi­na got approval for its first BSL‑4 lab in Wuhan, the first of sev­er­al planned BSL‑4 labs. “A lab­o­ra­to­ry in Wuhan is on the cusp of being cleared to work with the world’s most dan­ger­ous pathogens. The move is part of a plan to build between five and sev­en biosafe­ty level‑4 (BSL‑4) labs across the Chi­nese main­land by 2025, and has gen­er­at­ed much excite­ment, as well as some con­cerns. . . . Some sci­en­tists out­side Chi­na wor­ry about pathogens escap­ing, and the addi­tion of a bio­log­i­cal dimen­sion to geopo­lit­i­cal ten­sions between Chi­na and oth­er nations. [Ital­ics are mine‑D.E.] . . .”
2. As will be seen below, the pro­lif­er­a­tion of BSL‑4 labs has sparked wor­ries about “dual use” tech­nol­o­gy: ” . . . . The expan­sion of BSL-4-lab net­works in the Unit­ed States and Europe over the past 15 years — with more than a dozen now in oper­a­tion or under con­struc­tion in each region — also met with resis­tance, includ­ing ques­tions about the need for so many facil­i­ties. . . .”
3. The above-men­tioned Richard Ebright notes that the pro­lif­er­a­tion of BSL‑4 labs will spur sus­pi­cion of “dual use” tech­nol­o­gy, in which osten­si­ble med­ical research masks bio­log­i­cal war­fare research: ” . . . . But Ebright is not con­vinced of the need for more than one BSL‑4 lab in main­land Chi­na. He sus­pects that the expan­sion there is a reac­tion to the net­works in the Unit­ed States and Europe, which he says are also unwar­rant­ed. He adds that gov­ern­ments will assume that such excess capac­i­ty is for the poten­tial devel­op­ment of bioweapons. ‘These facil­i­ties are inher­ent­ly dual use,’ he says. . . .”

In the con­text of the above arti­cles, note that the Nation­al Insti­tutes of Health have also part­nered with CIA and the Pen­ta­gon, as under­scored by an arti­cle about a BSL‑4 lab at Boston Uni­ver­si­ty. Note that the U.S. and Europe have twelve BSL4 labs apiece, Tai­wan has two, while Chi­na has one:

1. As the arti­cle notes, as of 2007, the U.S. had “more than a dozen” BSL4 labs–China com­mis­sioned its first as of 2017. a ten­fold increase in fund­ing for BSL4 labs occurred because of the anthrax attacks of 2001. Those attacks might be seen as some­thing of a provo­ca­tion, spurring a dra­mat­ic increase in “dual use” biowar­fare research, under the cov­er of “legit­i­mate” medical/scientific research. In FTR #1128, we hypoth­e­sized about the milieu of Stephen Hat­fill and apartheid-linked inter­ests as pos­si­ble authors of a vec­tor­ing of New York City with Sars COV2: ” . . . . Before the anthrax mail­ings of 2001, the Unit­ed States had just two BSL4 labs—both with­in the razor-wire con­fines of gov­ern­ment-owned cam­pus­es. Now, thanks to a ten­fold increase in funding—from $200 mil­lion in 2001 to $2 bil­lion in 2006—more than a dozen such facil­i­ties can be found at uni­ver­si­ties and pri­vate com­pa­nies across the coun­try. . . .”
2. The Boston Uni­ver­si­ty lab exem­pli­fies the Pen­ta­gon and CIA pres­ence in BSL‑4 facil­i­ty “dual use”: ” . . . . But some sci­en­tists say that argu­ment obscures the true pur­pose of the cur­rent biode­fense boom: to study poten­tial bio­log­i­cal weapons. ‘The uni­ver­si­ty por­trays it as an emerg­ing infec­tious dis­ease lab,’ says David Ozonoff, a Boston Uni­ver­si­ty epi­demi­ol­o­gist whose office is right across the street from the new BSL4 facil­i­ty. ‘But they are talk­ing about study­ing things like small pox and inhala­tion anthrax, which pose no pub­lic health threat oth­er than as bioweapons.’ . . . The orig­i­nal NIH man­date for the lab indi­cat­ed that many groups—including the CIA and Depart­ment of Defense—would be allowed to use the lab for their own research, the nature of which BU might have lit­tle con­trol over. . . .”

Note, also that:

1. The WIV has part­nered with the U.S. Army’s Med­ical Research Insti­tute of Infec­tious Dis­eases, locat­ed at Ft. Det­rick.
2. In ear­ly August of 2019, short­ly before the record­ed start of the out­break in Wuhan, Chi­na, the U.S. Army Med­ical Research Insti­tute of Infec­tious Dis­eases at that facil­i­ty was closed down by the CDC due to mul­ti­ple safe­ty vio­la­tions.“All research at a Fort Det­rick lab­o­ra­to­ry that han­dles high-lev­el dis­ease-caus­ing mate­r­i­al, such as Ebo­la, is on hold indef­i­nite­ly after the Cen­ters for Dis­ease Con­trol and Pre­ven­tion found the orga­ni­za­tion failed to meet biosafe­ty stan­dards. . . . The CDC sent a cease and desist order in July. After USAMRIID received the order from the CDC, its reg­is­tra­tion with the Fed­er­al Select Agent Pro­gram, which over­sees dis­ease-caus­ing mate­r­i­al use and pos­ses­sion, was sus­pend­ed. That sus­pen­sion effec­tive­ly halt­ed all bio­log­i­cal select agents and tox­in research at USAMRIID . . . .”

Fol­low­ing the update on the WIV and BSL‑4 lab­o­ra­to­ries, we piv­ot to analy­sis of the ele­va­tion of remde­sivir as the “go-to” treat­ment du jour for Covid-19. Of para­mount impor­tance is the remark­able time­line: The DSMB (data safe­ty and mon­i­tor­ing board) ” . . . . the DSMB for the remde­sivir study did not ever meet for an inter­im effi­ca­cy analy­sis, Lane said. All patients had been enrolled by April 20. The data for a DSMB meet­ing was cut off on April 22. The DSMB met and, on April 27, it made a rec­om­men­da­tion to the NIAID. . . . That deci­sion, Lane said, led the NIAID to con­clude that patients who had been giv­en place­bo should be offered remde­sivir, some­thing that start­ed hap­pen­ing after April 28. . . .” 

As will be seen, it was on 4/29 that Joe Gro­gan resigned. (See below.)

When pos­i­tive news on a NIAID study on the drug remde­sivir were released–on 4/29–it drove broad gains in the stock mar­ket. In FTR #1131, we not­ed that dis­clo­sures con­cern­ing pos­i­tive news about Mod­er­na’s exper­i­men­tal Covid-19 vac­cine also proved to be a sim­i­lar dri­ver of the stock mar­ket, as well as of Mod­er­na’s stock.

Dis­cus­sion of the hard details of sev­er­al remde­sivir tri­als begins with dis­cus­sion of an NIAID tri­al that helped move the mar­kets, as seen above. The tri­al was a mod­est suc­cess, indi­cat­ing that recov­ery for recent­ly infect­ed patients was about 31% faster than for place­bo. There was no sig­nif­i­cant sta­tis­ti­cal dif­fer­ence in mortality–the most impor­tant mea­sure of effec­tive­ness accord­ing to many experts.

” . . . . Dur­ing an appear­ance along­side Pres­i­dent Trump in the Oval Office, Antho­ny Fau­ci, the direc­tor of NIAID, part of the Nation­al Insti­tutes of Health, said the data are a ‘very impor­tant proof of con­cept’ and that there was rea­son for opti­mism. He cau­tioned the data were not a ‘knock­out.’ At the same time, the study achieved its pri­ma­ry goal, which was to improve the time to recov­ery, which was reduced by four days for patients on remde­sivir. The pre­lim­i­nary data showed that the time to recov­ery was 11 days on remde­sivir com­pared to 15 days for place­bo, a 31% decrease. The mor­tal­i­ty rate for the remde­sivir group was 8%, com­pared to 11.6% for the place­bo group; that mor­tal­i­ty dif­fer­ence was not sta­tis­ti­cal­ly sig­nif­i­cant. . . .”

Next we present a Stat News arti­cle on the inter­nal delib­er­a­tions behind the deci­sions to mod­i­fy the NIAID study. Of par­tic­u­lar sig­nif­i­cance is the DSMB delib­er­a­tion. Note the time­line of the DSMB delib­er­a­tion, com­bined with the announce­ment on 4/29 that drove the mar­kets high­er.

1. The deci­sion was made to cut it short before the ques­tion of remdesivir’s impact on mor­tal­i­ty could be answered: ” . . . .The Nation­al Insti­tute of Aller­gy and Infec­tious Dis­eases has described to STAT in new detail how it made its fate­ful deci­sion: to start giv­ing remde­sivir to patients who had been assigned to receive a place­bo in the study, essen­tial­ly lim­it­ing researchers’ abil­i­ty to col­lect more data about whether the drug saves lives — some­thing the study, called ACTT‑1, sug­gests but does not prove. In the tri­al, 8% of the par­tic­i­pants giv­en remde­sivir died, com­pared with 11.6% of the place­bo group, a dif­fer­ence that was not sta­tis­ti­cal­ly sig­nif­i­cant. A top NIAID offi­cial said he had no regrets about the deci­sion. ‘There cer­tain­ly was una­nim­i­ty with­in the insti­tute that this was the right thing to do,’ said H. Clif­ford Lane, NIAID’s clin­i­cal direc­tor. . . .”
2. In addi­tion, patients sched­uled to receive place­bo received remde­sivir, instead. ” . . . . Steven Nis­sen, a vet­er­an tri­al­ist and car­di­ol­o­gist at the Cleve­land Clin­ic, dis­agreed that giv­ing place­bo patients remde­sivir was the right call. ‘I believe it is in society’s best inter­est to deter­mine whether remde­sivir can reduce mor­tal­i­ty, and with the release of this infor­ma­tion doing a place­bo-con­trolled tri­al to deter­mine if there is a mor­tal­i­ty ben­e­fit will be very dif­fi­cult,’ he said. ‘The ques­tion is: Was there a route, or is there a route, to deter­mine if the drug can pre­vent death?’ The deci­sion is ‘a lost oppor­tu­ni­ty,’ he said. . . .”
3. Steven Nis­sen was not alone in his crit­i­cism of the NIAID’s deci­sion. ” . . . . Peter Bach, the direc­tor of the Cen­ter for Health Pol­i­cy and Out­comes at Memo­r­i­al Sloan Ket­ter­ing Can­cer Cen­ter, agreed with Nis­sen. ‘The core under­stand­ing of clin­i­cal research par­tic­i­pa­tion and clin­i­cal research con­duct is we run the tri­al rig­or­ous­ly to pro­vide the most accu­rate infor­ma­tion about the right treat­ment,’ he said. And that answer, he argued, should ide­al­ly have deter­mined whether remde­sivir saves lives. The rea­son we have shut our whole soci­ety down, Bach said, is not to pre­vent Covid-19 patients from spend­ing a few more days in the hos­pi­tal. It is to pre­vent patients from dying. ‘Mor­tal­i­ty is the right end­point,’ he said. . . .”
4. Not only was the admin­is­tra­tion of remde­sivir instead of place­bo pri­or­i­tized, but the NIAID study itself was atten­u­at­ed! ” . . . . But the change in the study’s main goal also changed the way the study would be ana­lyzed. Now, the NIAID decid­ed, the analy­sis would be cal­cu­lat­ed when 400 patients out of the 1,063 patients the study enrolled had recov­ered. If remde­sivir turned out to be much more effec­tive than expect­ed, ‘inter­im’ analy­ses would be con­duct­ed at a third and two-thirds that num­ber.The job of review­ing these analy­ses would fall to a com­mit­tee of out­side experts on what is known as an inde­pen­dent data and safe­ty mon­i­tor­ing board, or DSMB. . . .”
5. The per­for­mance of the DSMB for the remde­sivir study is note­wor­thy: ” . . . . But the DSMB for the remde­sivir study did not ever meet for an inter­im effi­ca­cy analy­sis, Lane said. All patients had been enrolled by April 20. The data for a DSMB meet­ing was cut off on April 22. The DSMB met and, on April 27, it made a rec­om­men­da­tion to the NIAID. . . .”
6. The DSMB meet­ing on 4/27 deter­mined the switch from place­bo to remde­sivir. Of para­mount impor­tance is the fact that this was JUST BEFORE the 4/29 announce­ment that drove the mar­kets high­er and the same day on which key Trump aide–and for­mer Gilead Sci­ences lob­by­ist Joe Gro­gan resigned!” . . . . . That deci­sion, Lane said, led the NIAID to con­clude that patients who had been giv­en place­bo should be offered remde­sivir, some­thing that start­ed hap­pen­ing after April 28. . . .”
7. Dr. Ethan Weiss gave an accu­rate eval­u­a­tion of the NIAID study: ” . . . . ‘We’ve squan­dered an incred­i­ble oppor­tu­ni­ty to do good sci­ence,’ [Dr. Ethan] Weiss said. ‘If we could ever go back and do some­thing all over, it would be the infra­struc­ture to actu­al­ly learn some­thing. Because we’re not learn­ing enough.’ . . . .”

Next, we ana­lyze a STAT News excerpt that goes into more of the con­cerns about the Gilead study design.

The Gilead study was designed with­out any con­trol group, so the ques­tion of how much remde­sivir actu­al­ly helps sick patients (or doesn’t help) can’t be defin­i­tive­ly answered by that study.

The arti­cle also gives Gilead’s expla­na­tion for why they left out a con­trol group: due to the lim­it­ed sup­plies of the drug the com­pa­ny decid­ed to pri­or­i­tize on pro­duc­ing more of the drug itself rather than a place­bo con­trol. It’s an expla­na­tion that only makes sense if pro­duc­ing place­bo dos­es was some­how a sig­nif­i­cant tech­ni­cal chal­lenge, which seems dubi­ous.

Due to a lack of a con­trol group, the study instead focus­es on answer­ing the ques­tion of whether or not the recov­ery times for patients dif­fers between groups receiv­ing a 10-day course of the drug vs a 5‑day course. The patients were severe­ly ill but not on ven­ti­la­tors when enrolled in the study (so the patients that need the drug most weren’t test­ed). The pre­lim­i­nary results released Wednes­day sug­gest there is no dif­fer­ence between the recov­ery times for the two groups.

1. The Gilead study lacked a con­trol group: ” . . . .  But out­side experts in clin­i­cal tri­al design wor­ry that the results, instead of lead­ing to a clear pic­ture of whether the med­i­cine is effec­tive, will instead mud­dy the waters fur­ther. The main con­cern, they say, stems from the fact that the Gilead tri­al expect­ed to read out this week, which was con­duct­ed among patients with severe dis­ease, lacks a con­trol group — that is, patients who are ran­dom­ly assigned to receive the best treat­ment avail­able, but not remde­sivir. As designed, the only ran­dom­iza­tion is the dura­tion of treat­ment: either five days or 10 days of drug. With­out a true con­trol group of patients, many experts say, it will be dif­fi­cult to deter­mine whether remde­sivir is effec­tive. . . .”
2. The above-men­tioned Steven Nis­sen summed up the use­ful­ness of the Gilead tri­al. ” . . . . ‘The over­all study itself has lit­tle or no sci­en­tif­ic val­ue since all patients are receiv­ing the drug,’ said Steven Nis­sen, the chief aca­d­e­m­ic offi­cer at the Cleve­land Clin­ic and lead inves­ti­ga­tor of many tri­als for heart drugs that have been approved by the Food and Drug Admin­is­tra­tion. ‘The study, as designed, is essen­tial­ly use­less and can­not be used by the FDA for con­sid­er­a­tion of remde­sivir for approval to treat coro­n­avirus,’ Nis­sen said. . . .”
3. Gilead­’s spokesper­son alleged that the com­pa­ny had a lim­it­ed sup­ply of place­bo and remde­sivir. ” . . . . ‘In the ear­ly stages of the pan­dem­ic, we not only had a lim­it­ed sup­ply of remde­sivir but also a lim­it­ed sup­ply of the matched place­bo required for place­bo-con­trolled stud­ies,’ said Amy Flood, a Gilead spokesper­son. ‘We chose to pri­or­i­tize man­u­fac­tur­ing active drug over place­bo, and we pro­vid­ed our sup­ply of place­bo to Chi­na and NIAID for their stud­ies of remde­sivir.’ . . .”
4. A num­ber of crit­ics shared Steven Nis­sen’s opin­ion about the sci­en­tif­ic val­ue of the study. ” . . . . Crit­ics point to Gilead’s deci­sion to com­pare two groups giv­en remde­sivir for either five days or 10 days. The prob­lem with this strat­e­gy, they say, is that an inef­fec­tive drug that did noth­ing and a very effec­tive drug that con­sis­tent­ly helped patients over­come the virus would look the same in such a study. Only if the 10-day course were more effec­tive, or if it was worse because of side effects, would the study have any clear result. . . .”
5. Nis­sen was more opti­mistic about a sec­ond forth­com­ing Gilead tri­al. Sloan Ket­ter­ing’s Peter Bach did not share that opti­mism. ” . . . .Yet anoth­er tri­al in less sick patients, also run by Gilead, does have a con­trol group and may give a clear­er answer. Nis­sen sees ‘a rea­son­able study design.’ But Bach was more crit­i­cal, say­ing that even though that study has a con­trol group, the lack of a place­bo means the study might not be trust­wor­thy. That’s because its main goal, time to improve­ment of symp­toms, could be affect­ed by the per­cep­tions of clin­i­cians and the patients them­selves. Bach said the hos­pi­tals con­duct­ing the study ‘are eas­i­ly capa­ble of wrap­ping syringes in brown paper and blind­ing the whole thing. I don’t under­stand why you would run a tri­al like this.’ . . . .”

Although it was cut short due to the wan­ing of the pan­dem­ic in Chi­na, a WHO-leaked study was not encour­ag­ing with regard to remde­sivir’s effi­ca­cy as a treat­ment for Covid-19.

1. The Chi­nese study was a ram­dom­ized con­trolled tri­al: ” . . . . Encour­ag­ing data from patients in that study at the Uni­ver­si­ty of Chica­go were described by researchers at a vir­tu­al town hall and obtained by STAT last week. How­ev­er, unlike those data, these new results are from a ran­dom­ized con­trolled tri­al, the med­ical gold stan­dard. . . .”
2. The Chi­nese study found that remde­sivir was of no val­ue in pre­vent­ing Covid-19 deaths. As not­ed above, the effect of the drug on mor­tal­i­ty was the main con­sid­er­a­tion. Our soci­ety has not been shut down to afford peo­ple short­er stays in the hos­pi­tal, but to pre­vent death. ” . . . . Accord­ing to the sum­ma­ry of the Chi­na study, remde­sivir was ‘not asso­ci­at­ed with a dif­fer­ence in time to clin­i­cal improve­ment’ com­pared to a stan­dard of care con­trol. After one month, it appeared 13.9% of the remde­sivir patients had died com­pared to 12.8% of patients in the con­trol arm. The dif­fer­ence was not sta­tis­ti­cal­ly sig­nif­i­cant. . . .”
3. The Chi­nese study pro­duced a grim assess­ment of remde­sivir: ” . . . . ‘In this study of hos­pi­tal­ized adult patients with severe COVID-19 that was ter­mi­nat­ed pre­ma­ture­ly, remde­sivir was not asso­ci­at­ed with clin­i­cal or viro­log­i­cal ben­e­fits,’ the sum­ma­ry states. The study was ter­mi­nat­ed pre­ma­ture­ly because it was dif­fi­cult to enroll patients in Chi­na, where the num­ber of Covid-19 cas­es was decreas­ing. An out­side researcher said that the results mean that any ben­e­fit from remde­sivir is like­ly to be small. ‘If there is no ben­e­fit to remde­sivir in a study this size, this sug­gests that the over­all ben­e­fit of remde­sivir in this pop­u­la­tion with advanced infec­tion is like­ly to be small in the larg­er Gilead tri­al,’ said Andrew Hill, senior vis­it­ing research fel­low at Liv­er­pool Uni­ver­si­ty. . . .”

After dis­cussing a num­ber of prob­lems that Gilead Sci­ences may encounter in the pro­duc­tion of sig­nif­i­cant quan­ti­ties of remde­sivir to be effec­tive, the broad­cast con­cludes with dis­cus­sion of the inap­pro­pri­ate­ly-named “Sci­en­tists to Stop Covid-19.”

The remark­able han­dling of the NIAID study, the tim­ing of the announce­ment of the alto­geth­er lim­it­ed suc­cess of the atten­u­at­ed tri­al, and the rise in equi­ties as a result of the announce­ment may be best under­stood in the con­text of the role played in Trump pan­dem­ic deci­sion-mak­ing by an elite group of bil­lion­aires and scientists–including Peter Thiel and con­vict­ed felon Michael Milken (the “junk bond king”).

1. ” . . . . Call­ing them­selves ‘Sci­en­tists to Stop COVID-19,’ the col­lec­tion of top researchers, bil­lion­aires and indus­try cap­tains will act as an ‘ad hoc review board’ for the tor­rent of coro­n­avirus research, ‘weed­ing out’ flawed data before it reach­es pol­i­cy­mak­ers, the Wall Street Jour­nal report­ed on Mon­day. They are also act­ing as a go-between for phar­ma­ceu­ti­cal com­pa­nies seek­ing to build a com­mu­ni­ca­tion chan­nel with Trump admin­is­tra­tion offi­cials. The group . . . . has advised Nick Ayers, an aide to Vice Pres­i­dent Mike Pence, as well as oth­er agency heads, in the past month. Pence is head­ing up the White House coro­n­avirus task force. . . .”
2. ” . . . The brainy bunch is led by Thomas Cahill, a 33-year-old doc­tor who became a ven­ture cap­i­tal­ist . . . . Cahill’s clout comes from build­ing con­nec­tions through his invest­ment firm, New­path Part­ners, with Sil­i­con Valley’s Peter Thiel, the founder of Pay­Pal, and bil­lion­aire busi­ness­men Jim Palot­ta and Michael Milken. . . .”

Note that Thiel played a dom­i­nant role in bankrolling New­path Part­ners, and the oth­er finan­cial angel who ele­vat­ed Cahill–Brian Sheth–introduced him to Tom­my Hicks, Jr., the co-chair­man of the RNC. In FTR #‘s 1111 and 1112, we looked at Hicks’ net­work­ing with Steve Ban­non asso­ciate J. Kyle Bass, as well as his role in the inter-agency net­works dri­ving the anti-Chi­na effort.

” . . . . At the helm of the effort: The 33-year-old and very-much-under-the-radar ven­ture cap­i­tal­ist Tom Cahill, who leads life sci­ences-focused New­path Part­ners. Cahill com­plet­ed his M.D. and PhD at Duke Uni­ver­si­ty a mere two years ago before land­ing at blue-chip invest­ment firm Rap­tor Group through a friend. He went on to found New­path with some $125 mil­lion after impress­ing well-con­nect­ed names like ven­ture cap­i­tal­ist Peter Thiel and Vista Equi­ty Part­ners co-founder Bri­an Sheth. . . . It was through Sheth, for exam­ple, that Sci­en­tists to Stop Covid-19 con­nect­ed with the co-chair­man of the Repub­li­can Nation­al Com­mit­tee, Thomas Hicks Jr. . . .”

The fed­er­al gov­ern­men­t’s extreme focus on remde­sivir has been shaped, in large mea­sure, by the influ­ence of “Sci­en­tists to Stop COVID-19”:

1. “Sci­en­tists to Stop Covid-19” is shep­herd­ing remde­sivir: ” . . . . Sci­en­tists to Stop COVID-19 rec­om­mends that in this phase, the U.S. Food and Drug Admin­is­tra­tion (FDA) should work to coor­di­nate with Gilead phar­ma­ceu­ti­cals to focus on expe­dit­ing the results of clin­i­cal tri­als of remde­sivir, a drug iden­ti­fied as a poten­tial treat­ment for COVID-19. The group also rec­om­mends admin­is­ter­ing dos­es of the drug to patients in an ear­ly stage of infec­tion, and notes remde­sivir will essen­tial­ly be a place­hold­er until a more effec­tive treat­ment is pro­duced.
2. The group is doing so by atten­u­at­ing the reg­u­la­to­ry process for coro­n­avirus drugs: “Gov­ern­ment enti­ties and agen­cies appear to adhere to the rec­om­men­da­tions out­lined by the group, with the Jour­nal report­ing that the FDA and the Depart­ment of Vet­er­ans Affairs (VA) have imple­ment­ed some of the sug­ges­tions, name­ly relax­ing drug man­u­fac­tur­er reg­u­la­tions and require­ments for poten­tial coro­n­avirus treat­ment drugs. . . .”

We con­clude with a piece about the announce­ment of Grogan’s depar­ture.

” . . . . Gro­gan has served as the direc­tor of the White House Domes­tic Pol­i­cy Coun­cil since Feb­ru­ary 2019, over­see­ing a broad array of pol­i­cy issues includ­ing health care and reg­u­la­tion. . . . Gro­gan was one of the orig­i­nal mem­bers of the White House coro­n­avirus task force launched in late Jan­u­ary. . . . Gro­gan worked as a lob­by­ist for drug com­pa­ny Gilead Sci­ences before join­ing the Trump admin­is­tra­tion. . . .”

The depar­ture was announced in the Wall Street Jour­nal on the morn­ing of Wednes­day, April 29, the same day we got our first pub­lic reports of the NIAID clin­i­cal tri­al of remde­sivir that was pos­i­tive enough to show it short­ened the time to recov­ery and the same day the FDA grant­ed remde­sivir emer­gency use sta­tus. 

Note, again, the tim­ing of the DSM­B’s actions, as well as the imflu­ence of “Sci­en­tists to Stop Covid-19.”

1a. Research into the his­to­ry of GOF (gain-of-func­tion) work on bat coro­n­avirus­es at the Wuhan Insti­tute of Virol­o­gy indi­cates mul­ti­ple areas of U.S. intel­li­gence pres­ence in that work. 

It was pub­licly dis­closed in a 2017 paper that the US and Chi­na col­lab­o­rat­ed on “gain-of-func­tion” research on bat coro­n­avirus­es to infect humans and that the work received fund­ing from the Unit­ed States Agency for Inter­na­tion­al Development–a fre­quent cut-out for the CIA.

In addi­tion, the work was also fund­ed in part by the Nation­al Insti­tutes of Health, which have col­lab­o­rat­ed with both CIA and the Pen­ta­gon in BSL‑4 (Bio-Safe­ty-Lev­el 4) projects. 

The Wuhan Insti­tute of Virol­o­gy has also part­nered with the USAMRIID since the mid-1980’s.

Impor­tant to note is the fact that it was pub­lic infor­ma­tion that some of this work was done in a biosafe­ty-lev­el 2 lab­o­ra­to­ry, giv­ing an observ­er intent on under­tak­ing a bio­log­i­cal war­fare covert oper­a­tion against Chi­na use­ful field intel­li­gence about the vul­ner­a­bil­i­ty of WIV for such an “op.”

1. The inves­ti­ga­tion of infec­tiv­i­ty used unde­tectable meth­ods, negat­ing arti­cles claim­ing the virus could not have been genet­i­cal­ly engi­neered: ” Evi­dence has emerged that researchers at the Wuhan Insti­tute of Virol­o­gy (WIV) in Chi­na, work­ing in col­lab­o­ra­tion with sci­en­tists in the USA, have been genet­i­cal­ly engi­neer­ing bat virus­es for the past sev­er­al years to inves­ti­gate infec­tiv­i­ty – using unde­tectable meth­ods. . . . The evi­dence rebuts claims by jour­nal­ists and some sci­en­tists that the SARS-CoV­‑2 virus respon­si­ble for the cur­rent COVID-19 pan­dem­ic could not have been genet­i­cal­ly engi­neered because it lacks the ‘signs’ or ‘sig­na­tures’ that sup­pos­ed­ly would be left behind by genet­ic engi­neer­ing tech­niques. . . .”
2. Dr. Richard Ebright not­ed that the research was joint­ly fund­ed by the U.S. and Chi­na, that Peter Daszak (about whom we have voiced reser­va­tions in the past) was one of the Amer­i­can col­lab­o­ra­tors. Fur­ther­more, the research was fund­ed in part by USAID, a com­mon U.S. intel­li­gence cut-out. ” . . . . Dr Richard Ebright, an infec­tious dis­ease expert at Rut­gers Uni­ver­si­ty (USA), has alert­ed the pub­lic to evi­dence that WIV and US-based researchers were genet­i­cal­ly engi­neer­ing bat virus­es to inves­ti­gate their abil­i­ty to infect humans, using com­mon­ly used meth­ods that leave no sign or sig­na­ture of human manip­u­la­tion. Ebright flagged up a sci­en­tif­ic paper pub­lished in 2017 by WIV sci­en­tists, includ­ing Shi Zhengli, the virol­o­gist lead­ing the research into bat coro­n­avirus­es, work­ing in col­lab­o­ra­tion with Peter Daszak of the US-based Eco­Health Alliance. Fund­ing was shared between Chi­nese and US insti­tu­tions, the lat­ter includ­ing the US Nation­al Insti­tutes of Health and USAID. The researchers report hav­ing con­duct­ed virus infec­tiv­i­ty exper­i­ments where genet­ic mate­r­i­al is com­bined from dif­fer­ent vari­eties of SARS-relat­ed coro­n­avirus­es to form nov­el ‘chimeric’ ver­sions. This formed part of their research into what muta­tions were need­ed to allow cer­tain bat coro­n­avirus­es to bind to the human ACE2 recep­tor – a key step in the human infec­tiv­i­ty of SARS-CoV­‑2. . . .”
3. Fur­ther­more, the researchers used a type of genet­ic engi­neer­ing that leaves no sig­na­ture of human manip­u­la­tion: ” . . . . The WIV sci­en­tists did this, Ebright points out, ‘using ‘seam­less lig­a­tion’ pro­ce­dures that leave no sig­na­tures of human manip­u­la­tion’. This is note­wor­thy because it is a type of genet­ic engi­neer­ing that Ander­sen and his team exclud­ed from their inves­ti­ga­tion into whether SARS-CoV­‑2 could have been engi­neered – and it was in use at the very lab that is the prime sus­pect for a lab escape. . . .”
4. In addi­tion, Ebright high­lights the 2015 work done by Ralph Bar­ic in col­lab­o­ra­tion with WIV’s Shi Zhengli–a project we have dis­cussed at length in the past: ” . . . . A group of sci­en­tists from the Uni­ver­si­ty of North Car­oli­na in the USA, with the WIV’s Shi Zhengli as a col­lab­o­ra­tor, pub­lished a study in 2015 describ­ing sim­i­lar exper­i­ments involv­ing chimeric coro­n­avirus­es, which were also cre­at­ed using stan­dard unde­tectable genet­ic engi­neer­ing tech­niques. . . .”
5. Ebright also cites work done in a bio-safe­ty lev­el 2 lab­o­ra­to­ry. : ” . . . . Ebright points out that the paper states, ‘All work with the infec­tious virus was per­formed under biosafe­ty lev­el 2 con­di­tions’. This lev­el is suit­able for work involv­ing agents of only ‘mod­er­ate poten­tial haz­ard to per­son­nel and the envi­ron­ment’. . . .But they are not at fault in fail­ing to use BSL‑4 for this work, as SARS coro­n­avirus­es are not aerosol-trans­mit­ted. The work does, how­ev­er, fall under biosafe­ty lev­el 3, which is for work involv­ing microbes that can cause seri­ous and poten­tial­ly lethal dis­ease via inhala­tion. . . .”
6. Dr. Jonathan Lath­am under­scored the reser­va­tions expressed by many con­cern­ing “gain-of-func­tion” exper­i­ments on these kinds of coro­n­avirus­es: ” . . . . The bio­sci­en­tist Dr Jonathan Lath­am crit­i­cised the kind of research on bat coro­n­avirus­es that has been tak­ing place in Wuhan and the USA as ‘pro­vid­ing an evo­lu­tion­ary oppor­tu­ni­ty’ for such virus­es ‘to jump into humans’. Lath­am, who has a doc­tor­ate in virol­o­gy, argues that this kind of work is sim­ply ‘pro­vid­ing oppor­tu­ni­ties for con­t­a­m­i­na­tion events and leak­ages from labs, which hap­pen on a rou­tine basis’. . . .”

“Wuhan and US sci­en­tists used unde­tectable meth­ods of genet­ic engi­neer­ing on bat coro­n­avirus­es” by Jonathan Matthews and Claire Robin­son; GMWatch; 05/20/2020

Evi­dence has emerged that researchers at the Wuhan Insti­tute of Virol­o­gy (WIV) in Chi­na, work­ing in col­lab­o­ra­tion with sci­en­tists in the USA, have been genet­i­cal­ly engi­neer­ing bat virus­es for the past sev­er­al years to inves­ti­gate infec­tiv­i­ty – using unde­tectable meth­ods. The WIV is just a few miles from the Chi­nese city where the COVID-19 pan­dem­ic is thought to have orig­i­nat­ed and is the chief sus­pect in the pos­si­ble sce­nario that the virus emerged from a lab.

The evi­dence rebuts claims by jour­nal­ists and some sci­en­tists that the SARS-CoV­‑2 virus respon­si­ble for the cur­rent COVID-19 pan­dem­ic could not have been genet­i­cal­ly engi­neered because it lacks the “signs” or “sig­na­tures” that sup­pos­ed­ly would be left behind by genet­ic engi­neer­ing tech­niques.

Those mak­ing these claims cite as evi­dence a let­ter pub­lished in Nature Med­i­cine in March by Amer­i­can micro­bi­ol­o­gist Kris­t­ian Ander­sen and col­leagues. The arti­cle stat­ed that there was no evi­dence that the virus had been genet­i­cal­ly manip­u­lat­ed and con­clud­ed that it emerged through nat­ur­al muta­tion and selec­tion in ani­mal and human hosts.[1]

Typ­i­cal of the media response to the Nature Med­i­cine let­ter was an arti­cle pub­lished in The Sci­en­tist, which stat­ed, “there are no signs of genet­ic manip­u­la­tion in the SARS-CoV­‑2 genome”. The BBC also report­ed that “the study of the coro­n­avirus genome … found no signs it had been engi­neered”.

Oth­er experts, how­ev­er, have point­ed out that there are well known ways of manip­u­lat­ing the genet­ic mate­r­i­al of a virus with­out leav­ing any such signs.

Now Dr Richard Ebright, an infec­tious dis­ease expert at Rut­gers Uni­ver­si­ty (USA), has alert­ed the pub­lic to evi­dence that WIV and US-based researchers were genet­i­cal­ly engi­neer­ing bat virus­es to inves­ti­gate their abil­i­ty to infect humans, using com­mon­ly used meth­ods that leave no sign or sig­na­ture of human manip­u­la­tion.

Ebright flagged up a sci­en­tif­ic paper pub­lished in 2017 by WIV sci­en­tists, includ­ing Shi Zhengli, the virol­o­gist lead­ing the research into bat coro­n­avirus­es, work­ing in col­lab­o­ra­tion with Peter Daszak of the US-based Eco­Health Alliance. Fund­ing was shared between Chi­nese and US insti­tu­tions, the lat­ter includ­ing the US Nation­al Insti­tutes of Health and USAID. The researchers report hav­ing con­duct­ed virus infec­tiv­i­ty exper­i­ments where genet­ic mate­r­i­al is com­bined from dif­fer­ent vari­eties of SARS-relat­ed coro­n­avirus­es to form nov­el “chimeric” ver­sions. This formed part of their research into what muta­tions were need­ed to allow cer­tain bat coro­n­avirus­es to bind to the human ACE2 recep­tor – a key step in the human infec­tiv­i­ty of SARS-CoV­‑2.

The WIV sci­en­tists did this, Ebright points out, “using ‘seam­less lig­a­tion’ pro­ce­dures that leave no sig­na­tures of human manip­u­la­tion”. This is note­wor­thy because it is a type of genet­ic engi­neer­ing that Ander­sen and his team exclud­ed from their inves­ti­ga­tion into whether SARS-CoV­‑2 could have been engi­neered – and it was in use at the very lab that is the prime sus­pect for a lab escape.

A group of sci­en­tists from the Uni­ver­si­ty of North Car­oli­na in the USA, with the WIV’s Shi Zhengli as a col­lab­o­ra­tor, pub­lished a study in 2015 describ­ing sim­i­lar exper­i­ments involv­ing chimeric coro­n­avirus­es, which were also cre­at­ed using stan­dard unde­tectable genet­ic engi­neer­ing tech­niques.

Dr Michael Anto­niou, a Lon­don-based mol­e­c­u­lar geneti­cist, told us that these meth­ods of genet­ic engi­neer­ing have been com­mon­ly used for decades and do not leave any kind of “sig­na­ture”. Com­ment­ing on Ander­sen and his team’s omis­sion of these meth­ods from their arti­cle in Nature Med­i­cine, Dr Anto­niou told us, “This shows that these authors’ con­clu­sions about whether genet­ic engi­neer­ing could have been involved are not jus­ti­fied by the avail­able evi­dence.”

Min­i­mal biosafe­ty

Richard Ebright also flagged up anoth­er paper by WIV sci­en­tists that rais­es con­cerns. In a just-pub­lished pre-print, they describe inves­ti­gat­ing the abil­i­ty of spike pro­teins from bat SARS-relat­ed CoV (SARSr-CoV), among oth­er coro­n­avirus­es, to bind to bat and human ACE2 recep­tors – in oth­er words, how effi­cient­ly they infect humans. Ebright points out that the paper states, “All work with the infec­tious virus was per­formed under biosafe­ty lev­el 2 con­di­tions”. This lev­el is suit­able for work involv­ing agents of only “mod­er­ate poten­tial haz­ard to per­son­nel and the envi­ron­ment”.

The high­est lev­el of biosafe­ty is lev­el 4 (BSL‑4). This is for work with agents that could eas­i­ly be aerosol-trans­mit­ted with­in the lab­o­ra­to­ry and cause severe to fatal dis­ease in humans for which there are no avail­able vac­cines or treat­ments. Because the WIV has a BSL‑4 lab, many have assumed that work like this on infec­tious bat coro­n­avirus­es linked to SARS, a close­ly relat­ed coro­n­avirus to SARS-CoV­‑2, was being con­duct­ed at the high­est BSL‑4 lev­el of biose­cu­ri­ty. Clear­ly, as the WIV researchers state, this was not the case. But they are not at fault in fail­ing to use BSL‑4 for this work, as SARS coro­n­avirus­es are not aerosol-trans­mit­ted.

The work does, how­ev­er, fall under biosafe­ty lev­el 3, which is for work involv­ing microbes that can cause seri­ous and poten­tial­ly lethal dis­ease via inhala­tion. So it seems inex­cus­able that it was car­ried out only at the rel­a­tive­ly low biosafe­ty lev­el 2, which, as Ebright says, “pro­vides only min­i­mal pro­tec­tions against infec­tion of lab work­ers”.

Evo­lu­tion­ary oppor­tu­ni­ty for virus­es to jump to humans

The bio­sci­en­tist Dr Jonathan Lath­am crit­i­cised the kind of research on bat coro­n­avirus­es that has been tak­ing place in Wuhan and the USA as “pro­vid­ing an evo­lu­tion­ary oppor­tu­ni­ty” for such virus­es “to jump into humans”. Lath­am, who has a doc­tor­ate in virol­o­gy, argues that this kind of work is sim­ply “pro­vid­ing oppor­tu­ni­ties for con­t­a­m­i­na­tion events and leak­ages from labs, which hap­pen on a rou­tine basis”.

Giv­en that lab acci­dents are com­mon, includ­ing in Chi­na where the SARS virus has escaped from high-lev­el con­tain­ment facil­i­ties mul­ti­ple times, the details emerg­ing about the research activ­i­ties of the WIV and US sci­en­tists again under­line the need for a cred­i­ble inde­pen­dent inves­ti­ga­tion of the most foren­sic kind into the ori­gins of the cur­rent pan­dem­ic. And a broad­er inves­ti­ga­tion is also need­ed into the full range of bio­log­i­cal threats aris­ing from var­i­ous areas of poten­tial­ly haz­ardous but lax­ly reg­u­lat­ed biotech­nol­o­gy research.

Notes

1. In the Nature Med­i­cine let­ter, Ander­sen and col­leagues didn’t actu­al­ly look for – and fail to find – a “sign” or “sig­na­ture” of genet­ic engi­neer­ing, akin to a call­ing card left by a vis­i­tor. That’s no sur­prise, as they doubt­less knew that such a search would have been futile. What they actu­al­ly said was that if genet­ic engi­neer­ing had been involved, the virus would be dif­fer­ent from how it is: it would have been designed in a more “ide­al” way for human infec­tiv­i­ty, based on the pre­dic­tions of their com­put­er mod­el­ling sys­tem.

There are mas­sive prob­lems with this argu­ment, as experts have point­ed out. Com­put­er mod­el­ling pro­grams are only as good as the data that are put into them by humans, so it is not valid to assume that the pro­gram – or the humans that designed it – knows what an “ide­al” virus would look like in real-world con­di­tions.

The let­ter also stat­ed that if some­one were try­ing to engi­neer the virus as a pathogen, they would “prob­a­bly” have con­struct­ed it from the back­bone of a virus already known to be infec­tive to humans (note that “prob­a­bly” leaves plen­ty of wrig­gle room for alter­na­tive meth­ods of con­struct­ing a virus). But it’s pos­si­ble that if it was engi­neered from a back­bone, it was one that is not known out­side their research group. This is pos­si­ble if secre­cy were involved – for exam­ple, for bioweapons/biodefence research or com­mer­cial vac­cine devel­op­ment. . . .

1b. Note, again, that the whole world was informed back in 2017 that  dan­ger­ous research involv­ing the cre­ation of bat coro­n­avirus­es to infect humans was being car­ried out in Chi­na.  Note again, that the research was fund­ed in part by the US, includ­ing USAID–a fre­quent U.S. intel­li­gence cut-out; the NIH–which has active­ly col­lab­o­rat­ed with both CIA and Pen­ta­gon. The WIV has also part­nered with the USAMRIID.

Flash for­ward a cou­ple of years and we have a night­mare virus that ini­tial­ly appeared to pop up near­by the WIV, with the Trump admin­is­tra­tion aggres­sive­ly push­ing the idea that it escaped from that lab.

In that con­text, we note the fol­low­ing:

1. In 2017, Chi­na got approval for its first BSL‑4 lab in Wuhan, the first of sev­er­al planned BSL‑4 labs. “A lab­o­ra­to­ry in Wuhan is on the cusp of being cleared to work with the world’s most dan­ger­ous pathogens. The move is part of a plan to build between five and sev­en biosafe­ty level‑4 (BSL‑4) labs across the Chi­nese main­land by 2025, and has gen­er­at­ed much excite­ment, as well as some con­cerns. . . . Some sci­en­tists out­side Chi­na wor­ry about pathogens escap­ing, and the addi­tion of a bio­log­i­cal dimen­sion to geopo­lit­i­cal ten­sions between Chi­na and oth­er nations. [Ital­ics are mine‑D.E.] . . .”
2. As will be seen below, the pro­lif­er­a­tion of BSL‑4 labs has sparked wor­ries about “dual use” tech­nol­o­gy: ” . . . . The expan­sion of BSL-4-lab net­works in the Unit­ed States and Europe over the past 15 years — with more than a dozen now in oper­a­tion or under con­struc­tion in each region — also met with resis­tance, includ­ing ques­tions about the need for so many facil­i­ties. . . .”
3. The above-men­tioned Richard Ebright notes that the pro­lif­er­a­tion of BSL‑4 labs will spur sus­pi­cion of “dual use” tech­nol­o­gy, in which osten­si­ble med­ical research masks bio­log­i­cal war­fare research: ” . . . . But Ebright is not con­vinced of the need for more than one BSL‑4 lab in main­land Chi­na. He sus­pects that the expan­sion there is a reac­tion to the net­works in the Unit­ed States and Europe, which he says are also unwar­rant­ed. He adds that gov­ern­ments will assume that such excess capac­i­ty is for the poten­tial devel­op­ment of bioweapons. ‘These facil­i­ties are inher­ent­ly dual use,’ he says. . . .”

“Inside China’s pathogen lab Max­i­mum-secu­ri­ty biosafe­ty facil­i­ty nears approval, spark­ing excite­ment and con­cern.” by DAVID CYRANOSKI; Nature, Vol 542, pgs 300–401; 02/23/2017

A lab­o­ra­to­ry in Wuhan is on the cusp of being cleared to work with the world’s most dan­ger­ous pathogens. The move is part of a plan to build between five and sev­en biosafe­ty level‑4 (BSL‑4) labs across the Chi­nese main­land by 2025, and has gen­er­at­ed much excite­ment, as well as some con­cerns.

Some sci­en­tists out­side Chi­na wor­ry about pathogens escap­ing, and the addi­tion of a bio­log­i­cal dimen­sion to geopo­lit­i­cal ten­sions between Chi­na and oth­er nations. But Chi­nese micro­bi­ol­o­gists are cel­e­brat­ing their entrance to the elite cadre empow­ered to wres­tle with the world’s great­est bio­log­i­cal threats.

“It will offer more oppor­tu­ni­ties for Chi­nese researchers, and our con­tri­bu­tion on the BSL-4-lev­el pathogens will ben­e­fit the world,” says George Gao, direc­tor of the Chi­nese Acad­e­my of Sci­ences Key Lab­o­ra­to­ry of Path­o­gen­ic Micro­bi­ol­o­gy and Immunol­o­gy in Bei­jing. There are already two BSL‑4 labs in Tai­wan, but the Nation­al Bio-safe­ty Lab­o­ra­to­ry, Wuhan, would be the first on the Chi­nese main­land.

The lab was cer­ti­fied as meet­ing the stan­dards and cri­te­ria of BSL‑4 by the Chi­na Nation­al Accred­i­ta­tion Ser­vice for Con­for­mi­ty Assess­ment (CNAS) in Jan­u­ary. The CNAS exam­ined the lab’s infra­struc­ture, equip­ment and man­age­ment, says a CNAS rep­re­sen­ta­tive, paving the way for the Min­istry of Health to give its approval. A rep­re­sen­ta­tive from the min­istry says it will move slow­ly and cau­tious­ly; if the assess­ment goes smooth­ly, it could approve the lab­o­ra­to­ry by the end of June.

BSL‑4 is the high­est lev­el of bio­con­tain­ment: its cri­te­ria include fil­ter­ing air and treat­ing water and waste before they leave the lab­o­ra­to­ry, and stip­u­lat­ing that researchers change clothes and show­er before and after using lab facil­i­ties. Such labs are often con­tro­ver­sial. The first BSL‑4 lab in Japan was built in 1981, but oper­at­ed with low­er-risk pathogens until 2015, when safe­ty con­cerns were final­ly over­come.

The expan­sion of BSL-4-lab net­works in the Unit­ed States and Europe over the past 15 years — with more than a dozen now in oper­a­tion or under con­struc­tion in each region — also met with resis­tance, includ­ing ques­tions about the need for so many facil­i­ties.

The Wuhan lab cost 300 mil­lion yuan (US$44 mil­lion), and to allay safe­ty con­cerns it was built far above the flood plain and with the capac­i­ty to with­stand a magnitude‑7 earth­quake, although the area has no his­to­ry of strong earth­quakes. It will focus on the con­trol of emerg­ing dis­eases, store puri­fied virus­es and act as a World Health Orga­ni­za­tion ‘ref­er­ence lab­o­ra­to­ry’ linked to sim­i­lar labs around the world. “It will be a key node in the glob­al biosafe­ty-lab net­work,” says lab direc­tor Yuan Zhim­ing.

The Chi­nese Acad­e­my of Sci­ences approved the con­struc­tion of a BSL‑4 lab­o­ra­to­ry in 2003, and the epi­dem­ic of SARS (severe acute res­pi­ra­to­ry syn­drome) around the same time lent the project momen­tum. The lab was designed and con­struct­ed with French assis­tance as part of a 2004 coop­er­a­tive agree­ment on the pre­ven­tion and con­trol of emerg­ing infec­tious dis­eases. But the com­plex­i­ty of the project, China’s lack of expe­ri­ence, dif­fi­cul­ty in main­tain­ing fund­ing and long gov­ern­ment approval pro­ce­dures meant that con­struc­tion wasn’t fin­ished until the end of 2014.

The lab’s first project will be to study the BSL‑3 pathogen that caus­es Crimean–Congo haem­or­rhag­ic fever: a dead­ly tick-borne virus that affects live­stock across the world, includ-ing in north­west Chi­na, and that can jump to peo­ple.

Future plans include study­ing the pathogen that caus­es SARS, which also doesn’t require a BSL‑4 lab, before mov­ing on to Ebo­la and the West African Las­sa virus, which do. Some one mil­lion Chi­nese peo­ple work in Africa; the coun­try needs to be ready for any even­tu­al­i­ty, says Yuan. “Virus­es don’t know bor­ders.”

Gao trav­elled to Sier­ra Leone dur­ing the recent Ebo­la out­break, allow­ing his team to report the speed with which the virus mutat­ed into new strains (Y.-G. Tong et al. Nature 524,93–96; 2015). The Wuhan lab will give his group a chance to study how such virus­es cause dis­ease, and to devel­op treat­ments based on anti­bod­ies and small mol­e­cules, he says.

The oppor­tu­ni­ties for inter­na­tion­al col­lab­o­ra­tion, mean­while, will aid the genet­ic analy­sis and epi­demi­ol­o­gy of emer­gent dis­eases. “The world is fac­ing more new emerg­ing virus­es, and we need more con­tri­bu­tion from Chi­na,” says Gao. In par­tic­u­lar, the emer­gence of zoonot­ic virus­es — those that jump to humans from ani­mals, such as SARS or Ebo­la — is a con­cern, says Bruno Lina, direc­tor of the Vir­Path virol­o­gy lab in Lyon, France.

Many staff from the Wuhan lab have been train­ing at a BSL‑4 lab in Lyon, which some sci­en­tists find reas­sur­ing. And the facil­i­ty has already car­ried out a test-run using a low-risk virus.

But wor­ries sur­round the Chi­nese lab, too. The SARS virus has escaped from high-lev­el con­tain­ment facil­i­ties in Bei­jing mul­ti­ple times, notes Richard Ebright, a mol­e­c­u­lar biol­o­gist at Rut­gers Uni­ver­si­ty in Pis­cat­away, New Jer­sey. Tim Tre­van, founder of CHROME Biosafe­ty and Biose­cu­ri­ty Con­sult­ing in Dam­as­cus, Mary­land, says that an open cul-ture is impor­tant to keep­ing BSL‑4 labs safe, and he ques­tions how easy this will be in Chi­na, where soci­ety empha­sizes hier­ar­chy. “Diver­si­ty of view­point, flat struc­tures where every­one feels free to speak up and open­ness of infor­ma­tion are impor­tant,” he says.

Yuan says that he has worked to address this issue with staff. “We tell them the most impor­tant thing is that they report what they have or haven’t done,” he says. And the lab’s inter­na­tion­al col­lab­o­ra­tions will increase open­ness. “Trans­paren­cy is the basis of the lab,” he adds.

The plan to expand into a net­work height­ens such con­cerns. One BSL‑4 lab in Harbin is already await­ing accred­i­ta­tion; the next two are expect­ed to be in Bei­jing and Kun­ming, the lat­ter focused on using mon­key mod­els to study dis­ease.

Lina says that China’s size jus­ti­fies this scale, and that the oppor­tu­ni­ty to com­bine BSL‑4 research with an abun­dance of research mon­keys — Chi­nese researchers face less red tape than those in the West when it comes to research on pri­mates — could be pow­er­ful. “If you want to test vac­cines or antivi­rals, you need a non-human pri­mate mod­el,” says Lina.

But Ebright is not con­vinced of the need for more than one BSL‑4 lab in main­land Chi­na. He sus­pects that the expan­sion there is a reac­tion to the net­works in the Unit­ed States and Europe, which he says are also unwar­rant­ed. He adds that gov­ern­ments will assume that such excess capac­i­ty is for the poten­tial devel­op­ment of bioweapons.

“These facil­i­ties are inher­ent­ly dual use,” he says. The prospect of ramp­ing up oppor­tu­ni­ties to inject mon­keys with pathogens also wor­ries, rather than excites, him: “They can run, they can scratch, they can bite.” . . . .

1c. In the con­text of the above arti­cles, note that the Nation­al Insti­tutes of Health have also part­nered with CIA and the Pen­ta­gon, as under­scored by an arti­cle about a BSL‑4 lab at Boston Uni­ver­si­ty. Note that Europe and the U.S. have twelve BSL4 labs apiece. Tai­wan has two. Chi­na has one:

1. As the arti­cle notes, as of 2007, the U.S. had “more than a dozen” BSL4 labs–China com­mis­sioned its first as of 2017. a ten­fold increase in fund­ing for BSL4 labs occurred because of the anthrax attacks of 2001. Those attacks might be seen as some­thing of a provo­ca­tion, spurring a dra­mat­ic increase in “dual use” biowar­fare research, under the cov­er of “legit­i­mate” medical/scientific research. In FTR #1128, we hypoth­e­sized about the milieu of Stephen Hat­fill and apartheid-linked inter­ests as pos­si­ble authors of a vec­tor­ing of New York City with Sars COV2: ” . . . . Before the anthrax mail­ings of 2001, the Unit­ed States had just two BSL4 labs—both with­in the razor-wire con­fines of gov­ern­ment-owned cam­pus­es. Now, thanks to a ten­fold increase in funding—from $200 mil­lion in 2001 to $2 bil­lion in 2006—more than a dozen such facil­i­ties can be found at uni­ver­si­ties and pri­vate com­pa­nies across the coun­try. . . .”
2. The Boston Uni­ver­si­ty lab exem­pli­fies the Pen­ta­gon and CIA pres­ence in BSL‑4 facil­i­ty “dual use”: ” . . . . But some sci­en­tists say that argu­ment obscures the true pur­pose of the cur­rent biode­fense boom: to study poten­tial bio­log­i­cal weapons. ‘The uni­ver­si­ty por­trays it as an emerg­ing infec­tious dis­ease lab,’ says David Ozonoff, a Boston Uni­ver­si­ty epi­demi­ol­o­gist whose office is right across the street from the new BSL4 facil­i­ty. ‘But they are talk­ing about study­ing things like small pox and inhala­tion anthrax, which pose no pub­lic health threat oth­er than as bioweapons.’ . . . The orig­i­nal NIH man­date for the lab indi­cat­ed that many groups—including the CIA and Depart­ment of Defense—would be allowed to use the lab for their own research, the nature of which BU might have lit­tle con­trol over. . . .”

“High-Stakes Sci­ence” by Jeneen Inter­lan­di; Newsweek; 12/05/2007.

. . . . Before the anthrax mail­ings of 2001, the Unit­ed States had just two BSL4 labs—both with­in the razor-wire con­fines of gov­ern­ment-owned cam­pus­es. Now, thanks to a ten­fold increase in funding—from $200 mil­lion in 2001 to $2 bil­lion in 2006—more than a dozen such facil­i­ties can be found at uni­ver­si­ties and pri­vate com­pa­nies across the coun­try. . . .

. . . . But some sci­en­tists say that argu­ment obscures the true pur­pose of the cur­rent biode­fense boom: to study poten­tial bio­log­i­cal weapons. “The uni­ver­si­ty por­trays it as an emerg­ing infec­tious dis­ease lab,” says David Ozonoff, a Boston Uni­ver­si­ty epi­demi­ol­o­gist whose office is right across the street from the new BSL4 facil­i­ty. “But they are talk­ing about study­ing things like small pox and inhala­tion anthrax, which pose no pub­lic health threat oth­er than as bioweapons.” And when it comes to ter­ror­ism, Ozonoff says, more labs will only increase the threat of an attack. “There has been one seri­ous bioter­ror inci­dent,” he says. “That was anthrax, and it came from a biode­fense lab.” While the uni­ver­si­ty has repeat­ed­ly stat­ed that the new facil­i­ty will not house bioweapons research, that might not be a promise it can keep. The orig­i­nal NIH man­date for the lab indi­cat­ed that many groups—including the CIA and Depart­ment of Defense—would be allowed to use the lab for their own research, the nature of which BU might have lit­tle con­trol over. . . .

1d. The WIV has part­nered with the U.S. Army’s Med­ical Research Insti­tute of Infec­tious Dis­eases, locat­ed at Ft. Det­rick:

Wuhan Uni­ver­si­ty School of Basic Med­ical Sci­ences: Insti­tute of Med­ical Virol­o­gy

. . . . Since the midst of 1980’s, coop­er­at­ed with US Army Med­ical Research Insti­tute for Infec­tious Dis­eases . . .

1e. In ear­ly August of 2019, short­ly before the record­ed start of the out­break in Wuhan, Chi­na, the U.S. Army Med­ical Research Insti­tute of Infec­tious Dis­eases at that facil­i­ty was closed down by the CDC due to mul­ti­ple safe­ty vio­la­tions.“All research at a Fort Det­rick lab­o­ra­to­ry that han­dles high-lev­el dis­ease-caus­ing mate­r­i­al, such as Ebo­la, is on hold indef­i­nite­ly after the Cen­ters for Dis­ease Con­trol and Pre­ven­tion found the orga­ni­za­tion failed to meet biosafe­ty stan­dards. . . . The CDC sent a cease and desist order in July. After USAMRIID received the order from the CDC, its reg­is­tra­tion with the Fed­er­al Select Agent Pro­gram, which over­sees dis­ease-caus­ing mate­r­i­al use and pos­ses­sion, was sus­pend­ed. That sus­pen­sion effec­tive­ly halt­ed all bio­log­i­cal select agents and tox­in research at USAMRIID . . . .”

2a. When pos­i­tive news on a NIAID study on the drug remde­sivir were released, it drove broad gains in the stock mar­ket.

“Pos­si­ble Covid-19 Drug Pow­ers Mar­kets” [AP]; The New York Times; 4/30/2020; p. B2 [West­ern Edi­tion]. NB: The link is to the Boston Globe arti­cle from AP.

Stocks around the world whipped high­er, rid­ing a wave of opti­mism about a pos­si­ble COVID-19 treat­ment. The hope was so strong that investors side­stepped a report show­ing the out­break drove the US econ­o­my to its worst quar­ter­ly per­for­mance since the Great Reces­sion. The S&P 500 vault­ed 2.7 per­cent high­er and extend­ed a ral­ly that’s brought the US stock mar­ket to the brink of its best month in 45 years.

The spark for Wednesday’s ral­ly was a report that an exper­i­men­tal drug proved effec­tive against the new coro­n­avirus in a study run by the Nation­al Insti­tutes of Health. The nation’s top infec­tious dis­eases expert said the drug reduced the time it takes patients to recov­er, and it raised hopes that life around the world may even­tu­al­ly tip­toe back toward “nor­mal.” . . .

. . . . Gilead’s release about its remde­sivir drug hit mar­kets at the same moment as a gov­ern­ment report show­ing the US econ­o­my shrank at a 4.8 per­cent annu­al rate in the first three months of the year. . . .

3. Dis­cus­sion of the hard details of sev­er­al remde­sivir tri­als begins with dis­cus­sion of an NIAID tri­al that helped move the mar­kets, as seen above. The tri­al was a mod­est suc­cess, indi­cat­ing that recov­ery for recent­ly infect­ed patients was about 31% faster than for place­bo. There was no sig­nif­i­cant sta­tis­ti­cal dif­fer­ence in mortality–the most impor­tant mea­sure of effec­tive­ness accord­ing to many experts.

” . . . . Dur­ing an appear­ance along­side Pres­i­dent Trump in the Oval Office, Antho­ny Fau­ci, the direc­tor of NIAID, part of the Nation­al Insti­tutes of Health, said the data are a ‘very impor­tant proof of con­cept’ and that there was rea­son for opti­mism. He cau­tioned the data were not a ‘knock­out.’ At the same time, the study achieved its pri­ma­ry goal, which was to improve the time to recov­ery, which was reduced by four days for patients on remde­sivir. The pre­lim­i­nary data showed that the time to recov­ery was 11 days on remde­sivir com­pared to 15 days for place­bo, a 31% decrease. The mor­tal­i­ty rate for the remde­sivir group was 8%, com­pared to 11.6% for the place­bo group; that mor­tal­i­ty dif­fer­ence was not sta­tis­ti­cal­ly sig­nif­i­cant. . . .”

“Crit­i­cal study of Gilead’s Covid-19 drug shows patients are respond­ing to treat­ment, NIH says” by Matthew Her­p­er and Adam Feuer­stein; STAT News; 04/29/2020

A gov­ern­ment-run study of Gilead’s remde­sivir, per­haps the most close­ly watched exper­i­men­tal drug to treat the nov­el coro­n­avirus, showed that the med­i­cine is effec­tive against Covid-19, the dis­ease caused by the virus.

In a state­ment on Wednes­day, the Nation­al Insti­tute of Aller­gy and Infec­tious Dis­eases, which is con­duct­ing the study, said pre­lim­i­nary data show patients who received remde­sivir recov­ered faster than sim­i­lar patients who received place­bo.

The find­ing — although dif­fi­cult to ful­ly char­ac­ter­ize with­out full, detailed data for the study — would rep­re­sent the first treat­ment shown to improve out­comes in patients infect­ed with the virus that put the glob­al econ­o­my in a stand­still and killed at least 218,000 peo­ple world­wide.

Dur­ing an appear­ance along­side Pres­i­dent Trump in the Oval Office, Antho­ny Fau­ci, the direc­tor of NIAID, part of the Nation­al Insti­tutes of Health, said the data are a “very impor­tant proof of con­cept” and that there was rea­son for opti­mism. He cau­tioned the data were not a “knock­out.” At the same time, the study achieved its pri­ma­ry goal, which was to improve the time to recov­ery, which was reduced by four days for patients on remde­sivir.

The pre­lim­i­nary data showed that the time to recov­ery was 11 days on remde­sivir com­pared to 15 days for place­bo, a 31% decrease. The mor­tal­i­ty rate for the remde­sivir group was 8%, com­pared to 11.6% for the place­bo group; that mor­tal­i­ty dif­fer­ence was not sta­tis­ti­cal­ly sig­nif­i­cant.

That is “the first con­vinc­ing evi­dence that an antivi­ral drug can real­ly ben­e­fit Covid-19 patients, specif­i­cal­ly hos­pi­tal­ized Covid-19 patients,” said Fred­er­ick Hay­den, a pro­fes­sor emer­i­tus of clin­i­cal virol­o­gy and med­i­cine at the Uni­ver­si­ty of Vir­ginia School of Med­i­cine. “This will change the stan­dard of care in the Unit­ed States and oth­er coun­tries for the patients who have been shown to be ben­e­fit­ed,” he said, adding that deter­min­ing the exact group that should receive the drug will require fur­ther exam­i­na­tion of the data.

Over the past few weeks, there have been con­flict­ing reports about the poten­tial ben­e­fit of remde­sivir, a drug that was pre­vi­ous­ly tried in Ebo­la. As pre­vi­ous­ly report­ed by STAT, an ear­ly peek at Gilead’s study in severe Covid-19 patients, based on data from a tri­al at a Chica­go hos­pi­tal, sug­gest­ed patients were doing bet­ter than expect­ed on remde­sivir. Days lat­er, a sum­ma­ry of results from a study in Chi­na showed that patients on the drug did not improve more than those in a con­trol group.

…

But the NIAID study, which was not expect­ed to be released so soon, was by far the most impor­tant and rig­or­ous­ly designed test of remde­sivir in Covid-19. The study com­pared remde­sivir to place­bo in 800 patients, with nei­ther patients nor physi­cians know­ing who got the drug instead of a place­bo, mean­ing that uncon­scious bias­es will not affect the con­clu­sions.

The main goal of the study is the time until patients improve, with dif­fer­ent mea­sures of improve­ment depend­ing on how sick they were to begin with. While the result means that the drug helps patients improve faster, it is not pos­si­ble to say how dra­mat­ic those improve­ments are.

Scott Got­tlieb, the for­mer com­mis­sion­er of the Food and Drug Admin­is­tra­tion, said he expect­ed there was enough evi­dence for the agency to issue an “emer­gency use autho­riza­tion” for remde­sivir.

“Remde­sivir isn’t a home run but looks active and can be part of a tool­box of drugs and diag­nos­tics that sub­stan­tial­ly low­er our risk head­ing into the fall,” he said.

Aneesh Mehta, a physi­cian at Emory Uni­ver­si­ty and an inves­ti­ga­tor in the NIAID study, said the results were “robust enough” to report pre­lim­i­nary find­ings, but a full analy­sis of all the data will be required to ful­ly under­stand the drug’s effect. The time to recov­ery seen in the final analy­sis “could be short­er, it could be longer. We don’t know yet.” Mehta also expects the final results to do some analy­ses on which patients might ben­e­fit most from remde­sivir.

The FDA pre­vi­ous­ly issued an emer­gency autho­riza­tion for the malar­ia drug hydrox­y­chloro­quine to treat Covid-19, even though at least some stud­ies sug­gest­ed the med­i­cine was not effec­tive. “If hydrox­y­chloro­quine met [the emer­gency] stan­dard, then remde­sivir would have seemed to cross that line a while ago, espe­cial­ly in the set­ting of treat­ing crit­i­cal­ly ill patients,” Got­tlieb said.

Remde­sivir, which must be giv­en intra­venous­ly, is like­ly to remain a treat­ment for patients who are hos­pi­tal­ized. But it is also like­ly that it will be most effec­tive in patients who have been infect­ed more recent­ly, said Nahid Bhadelia, med­ical direc­tor of the spe­cial pathogens unit at Boston Med­ical Cen­ter.

“We know that with most antivi­ral med­ica­tions the ear­li­er you give it the bet­ter it is.” said Bhadelia, who had expe­ri­ence giv­ing remde­sivir as an exper­i­men­tal treat­ment for Ebo­la in Africa, where results are less encour­ag­ing. That means that bet­ter diag­nos­tic test­ing will be essen­tial to iden­ti­fy­ing patients who could ben­e­fit. “What will be impor­tant is that we find peo­ple on the out­pa­tient side,” Bhadelia said. “Again, test­ing becomes impor­tant, we want to have them come to the hos­pi­tal as soon as pos­si­ble.”

Although the data have not yet been released, it’s stan­dard pro­ce­dure for phar­ma­ceu­ti­cal and biotech­nol­o­gy com­pa­nies to release mar­ket-mov­ing infor­ma­tion as soon as they have it, due to reg­u­la­to­ry require­ments.

Gilead on Wednes­day did release data from its own study of remde­sivir in patients with severe Covid-19. This study showed sim­i­lar rates of clin­i­cal improve­ment in patients treat­ed with a five-day and 10-day course of remde­sivir, the com­pa­ny said.

“Unlike tra­di­tion­al drug devel­op­ment, we are attempt­ing to eval­u­ate an inves­ti­ga­tion­al agent along­side an evolv­ing glob­al pan­dem­ic. Mul­ti­ple con­cur­rent stud­ies are help­ing inform whether remde­sivir is a safe and effec­tive treat­ment for COVID-19 and how to best uti­lize the drug,” said Mer­dad Parsey, Gilead’s chief med­ical offi­cer, in a state­ment.

Gilead said that its own study in severe patients showed that it may be pos­si­ble to treat patients with a five-day treat­ment of remde­sivir, not the 10-day course that was used in the NIAID tri­al.

The company’s study is enrolling approx­i­mate­ly 6,000 par­tic­i­pants from 152 dif­fer­ent clin­i­cal tri­al sites all over the world. The data dis­closed Wednes­day are from 397 patients, with a sta­tis­ti­cal com­par­i­son of patient improve­ment between the two remde­sivir treat­ment arms — the five-day and 10-day treat­ment cours­es. Improve­ment was mea­sured using a sev­en-point numer­i­cal scale that encom­pass­es death (at worst) and dis­charge from hos­pi­tal (best out­come), with var­i­ous degrees of sup­ple­men­tal oxy­gen and intu­ba­tion in between.

The study design means that by itself it doesn’t reveal much about how well remde­sivir is work­ing, because there is no group of patients who were untreat­ed. The con­clu­sion is that the two dura­tions of treat­ment are basi­cal­ly the same.

Peter Bach, the direc­tor of the Cen­ter for Health Pol­i­cy and Out­comes at Memo­r­i­al Sloan Ket­ter­ing Med­ical Cen­ter, said he is eager to see the data from the NIAID study but renewed his crit­i­cism of Gilead’s severe study for lack­ing a con­trol group of untreat­ed patients. That would have allowed researchers to make impor­tant con­clu­sions about how the drug works that are just not pos­si­ble now, he said.

“They’ve squan­dered an unbe­liev­able oppor­tu­ni­ty,” Bach said. “It’s not going to tell us what to do with 80-year-olds with mul­ti­ple comor­bidi­ties com­pared to 30-year-olds who are oth­er­wise healthy. We’re still going to be founder­ing around in the dark, or at least in a dim room, when we could have learned more.”

In the study, the medi­an time to clin­i­cal improve­ment was 10 days in the five-day treat­ment group and 11 days in the 10-day treat­ment group. More than half of the patients in both groups were dis­charged from the hos­pi­tal by day 14. At day 14, 64.5% of the patients in the five-day group and 53.8% of the patients in the 10-day group achieved clin­i­cal recov­ery.

Patients in the tri­al gen­er­al­ly lived, though this may be because their ill­ness was not that severe to begin with. For most of the study, patients already on ven­ti­la­tors were not enrolled.

Eight per­cent of the patients treat­ed with five days of remde­sivir died, com­pared to 11% of the patients treat­ed for 10 days. Out­side of Italy, where 77 patients were treat­ed, the over­all mor­tal­i­ty rate across the entire study was 7%, Gilead said. Those mor­tal­i­ty rates are low­er than those seen in oth­er stud­ies, which have been in the teens and twen­ties.

Only 5% of patients in the five-day group and 10% in the 10-day group had side effects that led to a dis­con­tin­u­a­tion. The most com­mon bad effects — and it’s impos­si­ble to tell which were from the drug — were nau­sea and acute res­pi­ra­to­ry fail­ure. High liv­er enzymes occurred in 7.3% of patients, with 3% of patients dis­con­tin­u­ing the drug due to ele­vat­ed liv­er tests.

…

In the Chi­na study, also pub­lished Wednes­day in the Lancet, inves­ti­ga­tors found that remde­sivir “did not sig­nif­i­cant­ly improve the time to clin­i­cal improve­ment, mor­tal­i­ty, or time to clear­ance of virus in patients with seri­ous COVID-19 com­pared with place­bo.”

There was a 23% improve­ment in time to clin­i­cal improve­ment for remde­sivir com­pared to place­bo, but the dif­fer­ence was not sta­tis­ti­cal­ly sig­nif­i­cant. At the medi­an, remde­sivir-treat­ed patients improved in 20 days com­pared to 23 days for place­bo patients. At one month, 14% of the remde­sivir patients had died com­pared to 13% of the place­bo-treat­ed patients.

The Chi­na study enrolled patients with more severe Covid-19 than the study con­duct­ed by NIAID. The Chi­na study was also stopped ear­ly because of dif­fi­cul­ties enrolling patients as the pan­dem­ic waned in Chi­na.

Hay­den, the Uni­ver­si­ty of Vir­ginia virol­o­gist, was one of the inves­ti­ga­tors in the Chi­na study and point­ed to the sim­i­lar­i­ty of the results. He said that while the NIAID inves­ti­ga­tors had been able to enroll enough patients, the decrease in cas­es in Wuhan due to the lock­down had made that impos­si­ble. “I was struck by the con­sis­ten­cy,” he said. . . .

4. Next we present a Stat News arti­cle on the inter­nal delib­er­a­tions behind the deci­sions to mod­i­fy the NIAID study. Of par­tic­u­lar sig­nif­i­cance is the DSMB delib­er­a­tion. Note the time­line of the DSMB delib­er­a­tion, com­bined with the announce­ment on 4/29 that drove the mar­kets high­er.

1. The deci­sion was made to cut it short before the ques­tion of remdesivir’s impact on mor­tal­i­ty could be answered: ” . . . .The Nation­al Insti­tute of Aller­gy and Infec­tious Dis­eases has described to STAT in new detail how it made its fate­ful deci­sion: to start giv­ing remde­sivir to patients who had been assigned to receive a place­bo in the study, essen­tial­ly lim­it­ing researchers’ abil­i­ty to col­lect more data about whether the drug saves lives — some­thing the study, called ACTT‑1, sug­gests but does not prove. In the tri­al, 8% of the par­tic­i­pants giv­en remde­sivir died, com­pared with 11.6% of the place­bo group, a dif­fer­ence that was not sta­tis­ti­cal­ly sig­nif­i­cant. A top NIAID offi­cial said he had no regrets about the deci­sion. ‘There cer­tain­ly was una­nim­i­ty with­in the insti­tute that this was the right thing to do,’ said H. Clif­ford Lane, NIAID’s clin­i­cal direc­tor. . . .”
2. In addi­tion, patients sched­uled to receive place­bo received remde­sivir, instead. ” . . . . Steven Nis­sen, a vet­er­an tri­al­ist and car­di­ol­o­gist at the Cleve­land Clin­ic, dis­agreed that giv­ing place­bo patients remde­sivir was the right call. ‘I believe it is in society’s best inter­est to deter­mine whether remde­sivir can reduce mor­tal­i­ty, and with the release of this infor­ma­tion doing a place­bo-con­trolled tri­al to deter­mine if there is a mor­tal­i­ty ben­e­fit will be very dif­fi­cult,’ he said. ‘The ques­tion is: Was there a route, or is there a route, to deter­mine if the drug can pre­vent death?’ The deci­sion is ‘a lost oppor­tu­ni­ty,’ he said. . . .”
3. Steven Nis­sen was not alone in his crit­i­cism of the NIAID’s deci­sion. ” . . . .Peter Bach, the direc­tor of the Cen­ter for Health Pol­i­cy and Out­comes at Memo­r­i­al Sloan Ket­ter­ing Can­cer Cen­ter, agreed with Nis­sen. ‘The core under­stand­ing of clin­i­cal research par­tic­i­pa­tion and clin­i­cal research con­duct is we run the tri­al rig­or­ous­ly to pro­vide the most accu­rate infor­ma­tion about the right treat­ment,’ he said. And that answer, he argued, should ide­al­ly have deter­mined whether remde­sivir saves lives. The rea­son we have shut our whole soci­ety down, Bach said, is not to pre­vent Covid-19 patients from spend­ing a few more days in the hos­pi­tal. It is to pre­vent patients from dying. ‘Mor­tal­i­ty is the right end­point,’ he said. . . .”
4. Not only was the admin­is­tra­tion of remde­sivir instead of place­bo pri­or­i­tized, but the NIAID study itself was atten­u­at­ed! ” . . . . But the change in the study’s main goal also changed the way the study would be ana­lyzed. Now, the NIAID decid­ed, the analy­sis would be cal­cu­lat­ed when 400 patients out of the 1,063 patients the study enrolled had recov­ered. If remde­sivir turned out to be much more effec­tive than expect­ed, ‘inter­im’ analy­ses would be con­duct­ed at a third and two-thirds that num­ber.The job of review­ing these analy­ses would fall to a com­mit­tee of out­side experts on what is known as an inde­pen­dent data and safe­ty mon­i­tor­ing board, or DSMB. . . .”
5. The per­for­mance of the DSMB for the remde­sivir study is note­wor­thy: ” . . . . But the DSMB for the remde­sivir study did not ever meet for an inter­im effi­ca­cy analy­sis, Lane said. All patients had been enrolled by April 20. The data for a DSMB meet­ing was cut off on April 22. The DSMB met and, on April 27, it made a rec­om­men­da­tion to the NIAID. . . .”
6. The DSMB meet­ing on 4/27 deter­mined the switch from place­bo to remde­sivir. Of para­mount impor­tance is the fact that this was JUST BEFORE the 4/29 announce­ment that drove the mar­kets high­er and the same day on which key Trump aide–and for­mer Gilead Sci­ences lob­by­ist Joe Gro­gan resigned!” . . . . . That deci­sion, Lane said, led the NIAID to con­clude that patients who had been giv­en place­bo should be offered remde­sivir, some­thing that start­ed hap­pen­ing after April 28. . . .”
7. Dr. Ethan Weiss gave an accu­rate eval­u­a­tion of the NIAID study: ” . . . . ‘We’ve squan­dered an incred­i­ble oppor­tu­ni­ty to do good sci­ence,’ [Dr. Ethan] Weiss said. ‘If we could ever go back and do some­thing all over, it would be the infra­struc­ture to actu­al­ly learn some­thing. Because we’re not learn­ing enough.’ . . . .”

“Inside the NIH’s con­tro­ver­sial deci­sion to stop its big remde­sivir study” by Matthew Her­p­er; Stat News; 05/11/2020

The drug mak­er Gilead Sci­ences released a bomb­shell two weeks ago: A study con­duct­ed by a U.S. gov­ern­ment agency had found that the company’s exper­i­men­tal drug, remde­sivir, was the first treat­ment shown to have even a small effect against Covid-19.

Behind that ray of hope, though, was one of the tough­est quan­daries in med­i­cine: how to bal­ance the need to rig­or­ous­ly test a new med­i­cine for safe­ty and effec­tive­ness with the moral imper­a­tive to get patients a treat­ment that works as quick­ly as pos­si­ble. At the heart of the deci­sion about when to end the tri­al was a process that was — as is often in the case in clin­i­cal tri­als — by turns secre­tive and bureau­crat­ic.

The Nation­al Insti­tute of Aller­gy and Infec­tious Dis­eases has described to STAT in new detail how it made its fate­ful deci­sion: to start giv­ing remde­sivir to patients who had been assigned to receive a place­bo in the study, essen­tial­ly lim­it­ing researchers’ abil­i­ty to col­lect more data about whether the drug saves lives — some­thing the study, called ACTT‑1, sug­gests but does not prove. In the tri­al, 8% of the par­tic­i­pants giv­en remde­sivir died, com­pared with 11.6% of the place­bo group, a dif­fer­ence that was not sta­tis­ti­cal­ly sig­nif­i­cant.

A top NIAID offi­cial said he had no regrets about the deci­sion.

“There cer­tain­ly was una­nim­i­ty with­in the insti­tute that this was the right thing to do,” said H. Clif­ford Lane, NIAID’s clin­i­cal direc­tor. “While I think there might’ve been some dis­cus­sion, [because] every­one always tries to play devil’s advo­cate in these dis­cus­sions, I think there was a pret­ty uni­form opin­ion that this was what we should do.”

From the stand­point of the agency, he said, the study had answered the ques­tion it was designed to answer: The medi­an time that hos­pi­tal­ized Covid-19 patients on remde­sivir took to stop need­ing oxy­gen or exit the hos­pi­tal was, at 11 days, four days short­er than those who were on place­bo. “How many patients would we want to put at risk of dying,” he asked, for that last lit­tle bit of proof? Remde­sivir, he not­ed, was not a home run, but is prob­a­bly bet­ter than noth­ing.

Steven Nis­sen, a vet­er­an tri­al­ist and car­di­ol­o­gist at the Cleve­land Clin­ic, dis­agreed that giv­ing place­bo patients remde­sivir was the right call. “I believe it is in society’s best inter­est to deter­mine whether remde­sivir can reduce mor­tal­i­ty, and with the release of this infor­ma­tion doing a place­bo-con­trolled tri­al to deter­mine if there is a mor­tal­i­ty ben­e­fit will be very dif­fi­cult,” he said. “The ques­tion is: Was there a route, or is there a route, to deter­mine if the drug can pre­vent death?” The deci­sion is “a lost oppor­tu­ni­ty,” he said.

Peter Bach, the direc­tor of the Cen­ter for Health Pol­i­cy and Out­comes at Memo­r­i­al Sloan Ket­ter­ing Can­cer Cen­ter, agreed with Nis­sen. “The core under­stand­ing of clin­i­cal research par­tic­i­pa­tion and clin­i­cal research con­duct is we run the tri­al rig­or­ous­ly to pro­vide the most accu­rate infor­ma­tion about the right treat­ment,” he said. And that answer, he argued, should ide­al­ly have deter­mined whether remde­sivir saves lives.

The rea­son we have shut our whole soci­ety down, Bach said, is not to pre­vent Covid-19 patients from spend­ing a few more days in the hos­pi­tal. It is to pre­vent patients from dying. “Mor­tal­i­ty is the right end­point,” he said.

Most experts con­tact­ed by STAT expressed opin­ions that fell between Nis­sen and Lane, believ­ing that the deci­sion was a dif­fi­cult case, with sev­er­al defend­ing the NIAID.

“I think it was a real­ly tough call,” said Janet Wittes, a promi­nent sta­tis­ti­cian and the pres­i­dent of Sta­tis­tics Col­lab­o­ra­tive.

When the remde­sivir results were announced, the NIH said the data came from an “inter­im” analy­sis. This means that a study was stopped ear­ly because a drug’s ben­e­fit was so unde­ni­able that it would be uneth­i­cal to con­tin­ue the study. But Lane said this was incor­rect. The data come from a pre­lim­i­nary final analy­sis, a point at which the study would nor­mal­ly end.

The ACTT study (short for Adap­tive Covid-19 Treat­ment Tri­al) began in late Feb­ru­ary. The first patient dosed in the study was an Amer­i­can repa­tri­at­ed from the Dia­mond Princess, a British cruise ship where there was an out­break of more than 800 Covid-19 cas­es. By the terms of the study, hos­pi­tal­ized patients were ran­dom­ly assigned to receive either intra­venous remde­sivir or a place­bo. On day 15, the study would score patients on a scale from 1 (dead) to 8 (not hos­pi­tal­ized, with no restric­tions on activ­i­ties).

As results from oth­er Covid-19 stud­ies con­duct­ed in Chi­na start­ed to trick­le in, Lane and his team began to wor­ry that look­ing at the out­come on only the 15th day could lead the study to fail even if the drug was effec­tive. On March 22, with only 77 patients enrolled in the study, mem­bers of the NIAID team had a con­fer­ence call on which they decid­ed to change the mea­sure that would be used. Instead of mea­sur­ing patients on an eight-point scale on one day, the study would mea­sure the time until the patients scored one of the best three out­comes on the scale. This deci­sion was final­ized on April 2; it was post­ed to clinicaltrials.gov, a gov­ern­ment reg­istry of clin­i­cal tri­als, on April 16.

Iron­i­cal­ly, Lane said, the study would still have been pos­i­tive if the change had not been made. But the change in the study’s main goal also changed the way the study would be ana­lyzed. Now, the NIAID decid­ed, the analy­sis would be cal­cu­lat­ed when 400 patients out of the 1,063 patients the study enrolled had recov­ered. If remde­sivir turned out to be much more effec­tive than expect­ed, “inter­im” analy­ses would be con­duct­ed at a third and two-thirds that num­ber.

The job of review­ing these analy­ses would fall to a com­mit­tee of out­side experts on what is known as an inde­pen­dent data and safe­ty mon­i­tor­ing board, or DSMB. Though they gen­er­al­ly go unseen, DSMBs are among the most impor­tant and pow­er­ful forces in med­ical research. They are allowed to ana­lyze the data from a tri­al while it’s ongo­ing, even as drug com­pa­nies, doc­tors, and patients are kept from know­ing who is get­ting the med­i­cine and who is get­ting place­bo. These boards have two jobs: to make sure that patients aren’t being harmed by the exper­i­men­tal drug, and to ensure that it’s not already clear beyond a doubt that a med­i­cine is effec­tive.

Those deci­sions bring moments of tri­umph, despair, and, occa­sion­al­ly, con­fu­sion.

When Mer­ck decid­ed to with­draw the painkiller Vioxx in 2004, it was because a DSMB had rec­om­mend­ed stop­ping a study of the drug when it became clear the med­i­cine increased the risk of heart attacks and strokes. In 2014, when a study of the can­cer immunother­a­py Opdi­vo first proved that drug extend­ed sur­vival in melanoma, it was because a DSMB had found the result incon­tro­vert­ible and rec­om­mend­ed stop­ping the study.

But the DSMB for the remde­sivir study did not ever meet for an inter­im effi­ca­cy analy­sis, Lane said. All patients had been enrolled by April 20. The data for a DSMB meet­ing was cut off on April 22. The DSMB met and, on April 27, it made a rec­om­men­da­tion to the NIAID.

That rec­om­men­da­tion was not about whether the patients on place­bo should receive remde­sivir. Instead, the DSMB rec­om­mend­ed that in the next phase of the study, test­ing Eli Lilly’s arthri­tis drug Olu­mi­ant against remde­sivir, there was no need for a place­bo-only group.

That deci­sion, Lane said, led the NIAID to con­clude that patients who had been giv­en place­bo should be offered remde­sivir, some­thing that start­ed hap­pen­ing after April 28.

This is where Nis­sen and Bach dis­agree. There were 1,063 patients in the study, but only 480 had recov­ered at the time of the analy­sis. Researchers could have col­lect­ed more data, they argue, and per­haps have learned if remde­sivir saves lives. They were already close, both note. Results are con­sid­ered “sig­nif­i­cant” if a mea­sure called a p‑value is less than 0.05; the val­ue for mor­tal­i­ty in the pre­lim­i­nary analy­sis was 0.059. “How many patients would we want to put at risk of dying to get that 0.01 on the p‑value,” Lane retort­ed.

Marc Pfef­fer, a car­di­ol­o­gist at the Brigham and Women’s Hos­pi­tal in Boston, said he believes NIAID made the right call. He said that he was “very sym­pa­thet­ic” to the fact that researchers were get­ting this study done dur­ing a pan­dem­ic. “If you make the deci­sion that remde­sivir should be part of everybody’s ther­a­py in the next phase, then those vol­un­teers tak­ing the risks in the cur­rent tri­al should be switched to the active ther­a­py now con­sid­ered effec­tive,” he said.

…

Wittes, of Sta­tis­tics Col­lab­o­ra­tive, said she is glad she wasn’t on this DSMB, adding, “I don’t know where I would have come out.” And she said that when full results of the study are avail­able, she would be “shocked” if the NIAID had not done things prop­er­ly.

“I think there are groups of peo­ple who you’d real­ly respect who would not have stopped a study like this with­out a mor­tal­i­ty ben­e­fit,” Wittes said. “And I think you can argue that both ways.”

But she also wor­ried that the evi­dence might not be strong enough to make the deci­sion soci­ety is now mak­ing: that every new Covid-19 treat­ment must be giv­en with or com­pared to remde­sivir.

“The dan­ger is now it’s the treat­ment for every­body,” she said. “Now this is the base drug and every­thing is going to be that plus some­thing or the con­trol. I think we don’t know if it’s strong enough for it to be the stan­dard of care. I don’t think we know who should be treat­ed.”

Steven Joffe, an ethics expert at the Uni­ver­si­ty of Penn­syl­va­nia, said he believes the NIAID like­ly took the right steps in mak­ing its deci­sion to give remde­sivir to the place­bo patients. But he wor­ries about decid­ing to use time to improve­ment, not death, as the mea­sure of suc­cess, in the first place.

“I don’t find this end­point very com­pelling, and to me the real issue is the deci­sion to design the tri­al around the end­point of time to recov­ery defined in the way they defined recov­ery,” Joffe said. “To me, the deci­sions that are this weighty ought to be based on clin­i­cal­ly impor­tant end­points.”

All of this would nor­mal­ly wait until the full results were pub­lished, at which point the ros­ter of the DSMB may be revealed. (Lane would not share their names.) But what is unusu­al in this case is that, before the data are even ful­ly ana­lyzed, the FDA has autho­rized remdesivir’s use. A Chi­nese study, mean­while, failed to show remde­sivir had a ben­e­fit. Sev­er­al more stud­ies of the drug expect­ed to read out soon.

Ethan Weiss, a car­di­ol­o­gist at the Uni­ver­si­ty of Cal­i­for­nia, San Fran­cis­co, who trav­eled to New York two weeks ago to treat Covid-19 patients, said that he does wor­ry that we have missed “a fleet­ing oppor­tu­ni­ty” to under­stand how well remde­sivir works. “It is sad to me that we’re not going to get a com­plete answer about it.” But he said he also thinks the issue is “inside base­ball.” Remde­sivir, as sev­er­al experts have point­ed out, is not a game chang­er.

The real prob­lem, Weiss said, is not the han­dling of this par­tic­u­lar study but that there aren’t more like it. He said he wished the U.S. had built the infra­struc­ture need­ed to do more stud­ies like this when the pan­dem­ic in New York was at its height. He wished there were more stud­ies, with more DSMBs.

“We’ve squan­dered an incred­i­ble oppor­tu­ni­ty to do good sci­ence,” Weiss said. “If we could ever go back and do some­thing all over, it would be the infra­struc­ture to actu­al­ly learn some­thing. Because we’re not learn­ing enough.” . . . .

5. Here’s a STAT News excerpt that goes into more of the con­cerns about the Gilead study design.

The Gilead study was designed with­out any con­trol group, so the ques­tion of how much remde­sivir actu­al­ly helps sick patients (or doesn’t help) can’t be defin­i­tive­ly answered by that study.

The arti­cle also gives Gilead’s expla­na­tion for why they left out a con­trol group: due to the lim­it­ed sup­plies of the drug the com­pa­ny decid­ed to pri­or­i­tize on pro­duc­ing more of the drug itself rather than a place­bo con­trol. It’s an expla­na­tion that only makes sense if pro­duc­ing place­bo dos­es was some­how a sig­nif­i­cant tech­ni­cal chal­lenge, which seems dubi­ous.

Due to a lack of a con­trol group, the study instead focus­es on answer­ing the ques­tion of whether or not the recov­ery times for patients dif­fers between groups receiv­ing a 10-day course of the drug vs a 5‑day course. The patients were severe­ly ill but not on ven­ti­la­tors when enrolled in the study (so the patients that need the drug most weren’t test­ed). The pre­lim­i­nary results released Wednes­day sug­gest there is no dif­fer­ence between the recov­ery times for the two groups.

1. The Gilead study lacked a con­trol group: ” . . . .  But out­side experts in clin­i­cal tri­al design wor­ry that the results, instead of lead­ing to a clear pic­ture of whether the med­i­cine is effec­tive, will instead mud­dy the waters fur­ther. The main con­cern, they say, stems from the fact that the Gilead tri­al expect­ed to read out this week, which was con­duct­ed among patients with severe dis­ease, lacks a con­trol group — that is, patients who are ran­dom­ly assigned to receive the best treat­ment avail­able, but not remde­sivir. As designed, the only ran­dom­iza­tion is the dura­tion of treat­ment: either five days or 10 days of drug. With­out a true con­trol group of patients, many experts say, it will be dif­fi­cult to deter­mine whether remde­sivir is effec­tive. . . .”
2. The above-men­tioned Steven Nis­sen summed up the use­ful­ness of the Gilead tri­al. ” . . . . ‘The over­all study itself has lit­tle or no sci­en­tif­ic val­ue since all patients are receiv­ing the drug,’ said Steven Nis­sen, the chief aca­d­e­m­ic offi­cer at the Cleve­land Clin­ic and lead inves­ti­ga­tor of many tri­als for heart drugs that have been approved by the Food and Drug Admin­is­tra­tion. ‘The study, as designed, is essen­tial­ly use­less and can­not be used by the FDA for con­sid­er­a­tion of remde­sivir for approval to treat coro­n­avirus,’ Nis­sen said. . . .”
3. Gilead­’s spokesper­son alleged that the com­pa­ny had a lim­it­ed sup­ply of place­bo and remde­sivir. ” . . . . ‘In the ear­ly stages of the pan­dem­ic, we not only had a lim­it­ed sup­ply of remde­sivir but also a lim­it­ed sup­ply of the matched place­bo required for place­bo-con­trolled stud­ies,’ said Amy Flood, a Gilead spokesper­son. ‘We chose to pri­or­i­tize man­u­fac­tur­ing active drug over place­bo, and we pro­vid­ed our sup­ply of place­bo to Chi­na and NIAID for their stud­ies of remde­sivir.’ . . .”
4. A num­ber of crit­ics shared Steven Nis­sen’s opin­ion about the sci­en­tif­ic val­ue of the study. ” . . . . Crit­ics point to Gilead’s deci­sion to com­pare two groups giv­en remde­sivir for either five days or 10 days. The prob­lem with this strat­e­gy, they say, is that an inef­fec­tive drug that did noth­ing and a very effec­tive drug that con­sis­tent­ly helped patients over­come the virus would look the same in such a study. Only if the 10-day course were more effec­tive, or if it was worse because of side effects, would the study have any clear result. . . .”
5. Nis­sen was more opti­mistic about a sec­ond forth­com­ing Gilead tri­al. Sloan Ket­ter­ing’s Peter Bach did not share that opti­mism. ” . . . .Yet anoth­er tri­al in less sick patients, also run by Gilead, does have a con­trol group and may give a clear­er answer. Nis­sen sees ‘a rea­son­able study design.’ But Bach was more crit­i­cal, say­ing that even though that study has a con­trol group, the lack of a place­bo means the study might not be trust­wor­thy. That’s because its main goal, time to improve­ment of symp­toms, could be affect­ed by the per­cep­tions of clin­i­cians and the patients them­selves. Bach said the hos­pi­tals con­duct­ing the study ‘are eas­i­ly capa­ble of wrap­ping syringes in brown paper and blind­ing the whole thing. I don’t under­stand why you would run a tri­al like this.’ . . . .”

“The world wants answers on Gilead’s Covid-19 drug. Experts wor­ry next stud­ies may increase uncer­tain­ty” by Matthew Her­p­er and Adam Feuer­stein; STAT News; 04/27/2020

For weeks, the world has been eager­ly await­ing clin­i­cal tri­al results for one exper­i­men­tal drug, remde­sivir, to treat Covid-19. On some days, the entire stock mar­ket has moved up and down based on lim­it­ed amounts of data about the ther­a­py from Gilead Sci­ences.

The sig­nals, so far, have been con­tra­dic­to­ry. An ear­ly peek at one study, based on data from patients treat­ed at a Chica­go hos­pi­tal, sug­gest­ed patients were doing bet­ter than expect­ed on remde­sivir. Days lat­er, a sum­ma­ry of results from a study in Chi­na showed that patients on the drug did not improve more than those in a con­trol group.

A fuller pic­ture on remde­sivir is expect­ed any day now. Gilead has said that it will release data from one of its U.S. tri­als — the one from which the Chica­go results were dis­closed — by the end of this week. Even more data, from oth­er tri­als includ­ing the Chi­na study, could fol­low short­ly there­after.

But out­side experts in clin­i­cal tri­al design wor­ry that the results, instead of lead­ing to a clear pic­ture of whether the med­i­cine is effec­tive, will instead mud­dy the waters fur­ther.

The main con­cern, they say, stems from the fact that the Gilead tri­al expect­ed to read out this week, which was con­duct­ed among patients with severe dis­ease, lacks a con­trol group — that is, patients who are ran­dom­ly assigned to receive the best treat­ment avail­able, but not remde­sivir. As designed, the only ran­dom­iza­tion is the dura­tion of treat­ment: either five days or 10 days of drug. With­out a true con­trol group of patients, many experts say, it will be dif­fi­cult to deter­mine whether remde­sivir is effec­tive.

“The over­all study itself has lit­tle or no sci­en­tif­ic val­ue since all patients are receiv­ing the drug,” said Steven Nis­sen, the chief aca­d­e­m­ic offi­cer at the Cleve­land Clin­ic and lead inves­ti­ga­tor of many tri­als for heart drugs that have been approved by the Food and Drug Admin­is­tra­tion.

“The study, as designed, is essen­tial­ly use­less and can­not be used by the FDA for con­sid­er­a­tion of remde­sivir for approval to treat coro­n­avirus,” Nis­sen said.

Peter Bach, direc­tor of the Cen­ter for Health Pol­i­cy and Out­comes at Memo­r­i­al Sloan Ket­ter­ing Can­cer Cen­ter, called the sit­u­a­tion “frus­trat­ing.”

“For them to run the tri­al in severe but not include a con­trol group, it’s just such a waste,” Bach said.

The predica­ment is symp­to­matic of one of the biggest prob­lems in med­i­cine: Col­lect­ing data quick­ly can actu­al­ly slow things down if stud­ies are not designed in a way that gives clear, defin­i­tive answers.

Not every­one is as grim about prospects for use­ful data. Scott Got­tlieb, the for­mer com­mis­sion­er of the FDA and a fel­low at the Amer­i­can Enter­prise Insti­tute, defend­ed the Gilead study. He not­ed that while the tri­al expect­ed to read out first is “open label”— mean­ing that both doc­tors and patients know who is get­ting the drug and who is not — more tri­als are still being con­duct­ed.

“There’s a rig­or­ous, place­bo-con­trolled tri­al that’s now ful­ly enrolled and will read out soon, but there’s also a place for open label stud­ies to broad­en the safe­ty data­base and answer dis­crete ques­tions,” Got­tlieb said, refer­ring to a study spon­sored by the Nation­al Insti­tute for Aller­gy and Infec­tious Dis­eases.

Gilead says it had ‘only lim­it­ed sup­ply’

Gilead said that its study was nev­er meant to be the first word on remdesivir’s effi­ca­cy. Instead, it was meant to fol­low two stud­ies from Chi­na and the U.S. gov­ern­ment study, run by NIAID.

“In the ear­ly stages of the pan­dem­ic, we not only had a lim­it­ed sup­ply of remde­sivir but also a lim­it­ed sup­ply of the matched place­bo required for place­bo-con­trolled stud­ies,” said Amy Flood, a Gilead spokesper­son. “We chose to pri­or­i­tize man­u­fac­tur­ing active drug over place­bo, and we pro­vid­ed our sup­ply of place­bo to Chi­na and NIAID for their stud­ies of remde­sivir.”

Giv­en that three ran­dom­ized, place­bo-con­trolled tri­als were either under­way or about to start, Flood said, Gilead designed its own stud­ies to be open label. But this makes any con­clu­sion from a study far weak­er, because uncon­scious bias­es can affect the results.

Crit­ics point to Gilead’s deci­sion to com­pare two groups giv­en remde­sivir for either five days or 10 days. The prob­lem with this strat­e­gy, they say, is that an inef­fec­tive drug that did noth­ing and a very effec­tive drug that con­sis­tent­ly helped patients over­come the virus would look the same in such a study. Only if the 10-day course were more effec­tive, or if it was worse because of side effects, would the study have any clear result.

Got­tlieb defend­ed Gilead, argu­ing that increas­ing the size of the study from 400 patients to 6,000 expand­ed access to the drug at a time when it was need­ed to help with the pub­lic health emer­gency, but also allows the com­pa­ny to col­lect more rig­or­ous data. “I think it’s far bet­ter to pro­vide access in an open label set­ting than to mere­ly give drug away in an expand­ed access pro­to­col where you’re col­lect­ing min­i­mal or no data,” he said.

Yet anoth­er tri­al in less sick patients, also run by Gilead, does have a con­trol group and may give a clear­er answer. Nis­sen sees “a rea­son­able study design.” But Bach was more crit­i­cal, say­ing that even though that study has a con­trol group, the lack of a place­bo means the study might not be trust­wor­thy. That’s because its main goal, time to improve­ment of symp­toms, could be affect­ed by the per­cep­tions of clin­i­cians and the patients them­selves.

Bach said the hos­pi­tals con­duct­ing the study “are eas­i­ly capa­ble of wrap­ping syringes in brown paper and blind­ing the whole thing. I don’t under­stand why you would run a tri­al like this.”

The prob­lem of place­bo

When case num­bers in the U.S. start­ed to spike in mid-March, North­well Health, New York’s largest health care provider, imme­di­ate­ly staffed a 200-per­son unit to run Covid-19 clin­i­cal tri­als. Kevin Tracey, Northwell’s exec­u­tive vice pres­i­dent of research, said that the group’s goal was to con­duct rig­or­ous clin­i­cal tri­als that includ­ed con­trol groups. Why not have a place­bo arm in the Gilead-run study of severe patients?

“Obvi­ous­ly, that’s my first choice,” Tracey said. One rea­son it didn’t hap­pen was that every­one need­ed to move very fast.

“In a qui­et time when you have a few years to fig­ure out the best way to low­er cho­les­terol or the best way to treat arthri­tis, there’s a dia­logue between the inves­ti­ga­tors and the com­pa­ny and the FDA and you nego­ti­ate the tri­al design,” Tracey said. “We didn’t do that with Gilead, in this case, because our hos­pi­tals were fill­ing up with peo­ple who were dying.”

But Tracey points to anoth­er prob­lem, too. He said that more severe­ly affect­ed patients and their fam­i­lies, hav­ing read opti­mistic news reports about a med­i­cine, may not agree to be ran­dom­ly assigned to place­bo.

“That’s a real­i­ty,” he said. “You know that your moth­er, your wife, or your father, your broth­er is in the bed dying and you’re sup­posed to sign the papers that say you might get a place­bo? No thank you, a lot of peo­ple say.”

At the same time, it can be hard to answer ques­tions with­out ran­dom­ized data, and even then results can be con­fus­ing.

What to expect from Gilead’s study

Gilead’s severe Covid-19 study is enrolling approx­i­mate­ly 6,000 par­tic­i­pants from 152 dif­fer­ent clin­i­cal tri­al sites all over the world. The pri­ma­ry analy­sis to be dis­closed this week is expect­ed to encom­pass data from at least 400 patients, with a sta­tis­ti­cal com­par­i­son of patient improve­ment between the two remde­sivir treat­ment arms — the five-day and 10-day treat­ment course. Improve­ment will be mea­sured using a sev­en-point numer­i­cal scale that encom­pass­es death (at worst) and dis­charge from hos­pi­tal (best out­come), with var­i­ous degrees of sup­ple­men­tal oxy­gen and intu­ba­tion in between.

Video footage of a town hall at the Uni­ver­si­ty of Chica­go, seen by STAT, pro­vides some clues about what the results might bring. The researcher speak­ing in the video, Kath­leen Mul­lane from the Uni­ver­si­ty of Chica­go, said, “Most of our patients are severe and most of them are leav­ing at six days, so that tells us dura­tion of ther­a­py doesn’t have to be 10 days. We have very few that went out 10 days, maybe three.”

If Chicago’s expe­ri­ence holds true at the oth­er hos­pi­tals par­tic­i­pat­ing in Gilead’s study, there will be lit­tle or no dif­fer­ence in patient improve­ment between the two remde­sivir arms, mak­ing the com­par­i­son unin­ter­pretable.

That, though, will not be the end of the con­ver­sa­tion or the debate.

Gilead could also pro­vide addi­tion­al analy­ses on the time to clin­i­cal improve­ment for dif­fer­ent sub­sets of remde­sivir patients, based on dis­ease sever­i­ty, onset of symp­toms, or how quick­ly treat­ment was start­ed. With­out a con­trol arm, these data will be hard to inter­pret on their own.

One approach: com­pare to oth­er tri­als, like the 199-patient study of the HIV drug lopinavir that was pub­lished in the New Eng­land Jour­nal of Med­i­cine in March. In the study con­duct­ed in Chi­na, lopinavir was 31% bet­ter than stan­dard of care in time to clin­i­cal improve­ment, but the result was not sta­tis­ti­cal­ly sig­nif­i­cant. Mor­tal­i­ty was sim­i­lar, with 19% of lopinavir-treat­ed patients ver­sus 25% of stan­dard of care patients dead after one month.

Baird ana­lyst Bri­an Sko­r­ney, for instance, points out that 79% of the lopinavir-treat­ed patients were cured at one month, yet there was still no sig­nif­i­cant dif­fer­ence from the 70% cure rate in the con­trol arm. This sug­gests that high rates of patient recov­ery should be expect­ed, and that remde­sivir — a mod­est­ly effec­tive antivi­ral at best — will not make a big dif­fer­ence.

But RBC Cap­i­tal biotech ana­lyst Bri­an Abra­hams sug­gests using the con­trol arm from the lopinavir tri­als as an admit­ted­ly rough com­para­tor when the Gilead data are released.

At sev­en days, 2% of the patients treat­ed with stan­dard of care showed a clin­i­cal improve­ment, increas­ing to 30% at day 14 and 70% at day 28. If remde­sivir improves upon those results, per­haps dou­bling the time to clin­i­cal improve­ment at day 14, that might be seen as sug­gest­ing a ben­e­fit, Abra­hams believes.

Umer Raf­fat, an ana­lyst at Ever­core ISI, push­es back against the con­clu­sion that lopinavir failed in the Chi­na study — which might bode well for remde­sivir. Raf­fat points to an analy­sis in the NEJM study that showed in a small group of less sick patients treat­ed before their symp­toms wors­ened sig­nif­i­cant­ly, the lopinavir mor­tal­i­ty rate was 45% low­er.

Antivi­ral med­i­cines should be more effec­tive when giv­en ear­li­er. This is what Gilead is try­ing to do with remde­sivir in its severe Covid-19 study. The com­pa­ny is expect­ed to report mor­tal­i­ty rates when it announces results lat­er this week. If remde­sivir low­ers mor­tal­i­ty to 10–15% from the mid-20% range report­ed in oth­er stud­ies, that might also sug­gest a ben­e­fit.

Com­par­isons across dif­fer­ent clin­i­cal tri­als may help paint a clear­er pic­ture of remdesivir’s effi­ca­cy, but they’re not like­ly to per­suade FDA to approve the drug. That will only come from pos­i­tive data in sub­se­quent clin­i­cal tri­als.

What to expect: the Chi­na-run severe study

The tri­al in severe patients con­duct­ed in Chi­na — the one acci­den­tal­ly post­ed on the WHO’s web­site last week — failed to show that remde­sivir sped the time it took for patients to improve. After one month, it appeared 13.9% of the remde­sivir patients had died com­pared to 12.8% of patients in the con­trol arm. The dif­fer­ence was not sta­tis­ti­cal­ly sig­nif­i­cant.

But the WHO did not post full data; rather, it was an abstract of the study and pub­lished with­out the full man­u­script. It’s pos­si­ble that the pub­lished ver­sion will be dif­fer­ent.

It’s even pos­si­ble this study will be sup­port­ive of some effect for remde­sivir. The key is a sta­tis­tic, known as a haz­ard ratio, show­ing that the time to clin­i­cal improve­ment for patients in one group was 23% more than the oth­er. The key ques­tion is whether patients did bet­ter on remde­sivir or place­bo.

Raf­fat, the Ever­core ISI ana­lyst, obtained a copy of the study pro­to­col, a plan for how it was going to be run, and wrote in a note to the bank’s clients that this fig­ure was planned to be 1.4 if remde­sivir were to have a sta­tis­ti­cal­ly sig­nif­i­cant ben­e­fit. If that holds true, the 1.23 fig­ure means that the study just missed show­ing the drug was effec­tive, leav­ing hope that future stud­ies could show the drug would be effec­tive.

“It’s not a sil­ver bul­let, but I do believe remde­sivir is active,” Raf­fat said on a pod­cast for investors Fri­day. . . .

6. Although it was cut short due to the wan­ing of the pan­dem­ic in Chi­na, a WHO-leaked study was not encour­ag­ing with regard to remde­sivir’s effi­ca­cy as a treat­ment for Covid-19.

1. The Chi­nese study was a ram­dom­ized con­trolled tri­al: ” . . . . Encour­ag­ing data from patients in that study at the Uni­ver­si­ty of Chica­go were described by researchers at a vir­tu­al town hall and obtained by STAT last week. How­ev­er, unlike those data, these new results are from a ran­dom­ized con­trolled tri­al, the med­ical gold stan­dard. . . .”
2. The Chi­nese study found that remde­sivir was of no val­ue in pre­vent­ing Covid-19 deaths. As not­ed above, the effect of the drug on mor­tal­i­ty was the main con­sid­er­a­tion. Our soci­ety has not been shut down to afford peo­ple short­er stays in the hos­pi­tal, but to pre­vent death. ” . . . . Accord­ing to the sum­ma­ry of the Chi­na study, remde­sivir was ‘not asso­ci­at­ed with a dif­fer­ence in time to clin­i­cal improve­ment’ com­pared to a stan­dard of care con­trol. After one month, it appeared 13.9% of the remde­sivir patients had died com­pared to 12.8% of patients in the con­trol arm. The dif­fer­ence was not sta­tis­ti­cal­ly sig­nif­i­cant. . . .”
3. The Chi­nese study pro­duced a grim assess­ment of remde­sivir: ” . . . . ‘In this study of hos­pi­tal­ized adult patients with severe COVID-19 that was ter­mi­nat­ed pre­ma­ture­ly, remde­sivir was not asso­ci­at­ed with clin­i­cal or viro­log­i­cal ben­e­fits,’ the sum­ma­ry states. The study was ter­mi­nat­ed pre­ma­ture­ly because it was dif­fi­cult to enroll patients in Chi­na, where the num­ber of Covid-19 cas­es was decreas­ing. An out­side researcher said that the results mean that any ben­e­fit from remde­sivir is like­ly to be small. ‘If there is no ben­e­fit to remde­sivir in a study this size, this sug­gests that the over­all ben­e­fit of remde­sivir in this pop­u­la­tion with advanced infec­tion is like­ly to be small in the larg­er Gilead tri­al,’ said Andrew Hill, senior vis­it­ing research fel­low at Liv­er­pool Uni­ver­si­ty. . . .”

“New data on Gilead’s remde­sivir, released by acci­dent, show no ben­e­fit for coro­n­avirus patients. Com­pa­ny still sees rea­son for hope” by Ed Sil­ver­man, Adam Feuer­stein, and Matthew Her­p­er; STAT; 04/23/2020

The antivi­ral med­i­cine remde­sivir from Gilead Sci­ences failed to speed the improve­ment of patients with Covid-19 or pre­vent them from dying, accord­ing to results from a long-await­ed clin­i­cal tri­al con­duct­ed in Chi­na. Gilead, how­ev­er, said the data sug­gest a “poten­tial ben­e­fit.”

A sum­ma­ry of the study results was inad­ver­tent­ly post­ed to the web­site of the World Health Orga­ni­za­tion and seen by STAT on Thurs­day, but then removed.

“A draft man­u­script was pro­vid­ed by the authors to WHO and inad­ver­tent­ly post­ed on the web­site and tak­en down as soon as the mis­take was noticed. The man­u­script is now under­go­ing peer review and we are wait­ing for a final ver­sion before WHO com­ments on it,” said WHO spokesper­son Daniela Bagozzi.

Gilead spokesper­son Amy Flood said the com­pa­ny believes “the post includ­ed inap­pro­pri­ate char­ac­ter­i­za­tion of the study.” Because the study was stopped ear­ly because it had too few patients, she said, it can­not “enable sta­tis­ti­cal­ly mean­ing­ful con­clu­sions.” How­ev­er, she said, “trends in the data sug­gest a poten­tial ben­e­fit for remde­sivir, par­tic­u­lar­ly among patients treat­ed ear­ly in dis­ease.”

The data (for details, see screen­shot below) will be close­ly scru­ti­nized but are also like­ly imper­fect. The study was ter­mi­nat­ed pre­ma­ture­ly, which could have affect­ed the results. The con­text that would be pro­vid­ed by a full man­u­script is miss­ing, and the data have not been reviewed as nor­mal­ly occurs before pub­li­ca­tion.

Many stud­ies are being run to test remde­sivir, and this one will not be the final word. Results are expect­ed soon from a Gilead-run study in severe Covid-19 patients, although that study may be dif­fi­cult to inter­pret because the drug is not com­pared to patients receiv­ing only stan­dard treat­ment. Encour­ag­ing data from patients in that study at the Uni­ver­si­ty of Chica­go were described by researchers at a vir­tu­al town hall and obtained by STAT last week. How­ev­er, unlike those data, these new results are from a ran­dom­ized con­trolled tri­al, the med­ical gold stan­dard.

Gilead is also run­ning a study with a con­trol group in more mod­er­ate Covid-19 patients, and the Nation­al Insti­tute of Aller­gy and Infec­tious Dis­eases is run­ning a study that com­pares remde­sivir to place­bo. There are even more stud­ies of the drug ongo­ing.

Accord­ing to the sum­ma­ry of the Chi­na study, remde­sivir was “not asso­ci­at­ed with a dif­fer­ence in time to clin­i­cal improve­ment” com­pared to a stan­dard of care con­trol. After one month, it appeared 13.9% of the remde­sivir patients had died com­pared to 12.8% of patients in the con­trol arm. The dif­fer­ence was not sta­tis­ti­cal­ly sig­nif­i­cant.

“In this study of hos­pi­tal­ized adult patients with severe COVID-19 that was ter­mi­nat­ed pre­ma­ture­ly, remde­sivir was not asso­ci­at­ed with clin­i­cal or viro­log­i­cal ben­e­fits,” the sum­ma­ry states. The study was ter­mi­nat­ed pre­ma­ture­ly because it was dif­fi­cult to enroll patients in Chi­na, where the num­ber of Covid-19 cas­es was decreas­ing.

An out­side researcher said that the results mean that any ben­e­fit from remde­sivir is like­ly to be small.

“If there is no ben­e­fit to remde­sivir in a study this size, this sug­gests that the over­all ben­e­fit of remde­sivir in this pop­u­la­tion with advanced infec­tion is like­ly to be small in the larg­er Gilead tri­al,” said Andrew Hill, senior vis­it­ing research fel­low at Liv­er­pool Uni­ver­si­ty.

He added that the results of the study should be pooled with larg­er stud­ies being con­duct­ed by Gilead using a tech­nique called meta-analy­sis to allow for “a bal­anced view of the effi­ca­cy of remde­sivir from all ran­dom­ized tri­als.”

…

As orig­i­nal­ly designed, the Chi­na study was meant to enroll 453 patients. The patients were allowed to enter the study up to 12 days from the onset of Covid-19 symp­toms. Once enrolled, the patients were ran­dom­ized in a dou­ble-blind fash­ion and were treat­ed with dai­ly infu­sions of remde­sivir or a place­bo for 10 days.

The pri­ma­ry goal is to show that the drug is bet­ter than place­bo at improv­ing symp­toms with­in 28 days. That improve­ment is mea­sured with a six-point scor­ing sys­tem rang­ing from hos­pi­tal dis­charge (a score of 1) to death (a score of 6). In order to count as some­one who respond­ed to the drug, a patient must improve by at least two points. Patients can remain hos­pi­tal­ized at the end of the 28-day peri­od of the clin­i­cal tri­al but still improve enough clin­i­cal­ly — no longer need­ing intu­ba­tion or sup­ple­men­tal oxy­gen, for exam­ple — to count as a respon­der.

Accord­ing to the abstract, 158 patients received remde­sivir and 79 patients were in the con­trol arm; one patient in the con­trol arm with­drew before receiv­ing treat­ment. The abstract said that for time to clin­i­cal improve­ment, the haz­ard ratio was 1.23, which would nor­mal­ly mean the patients on remde­sivir improved more slow­ly than those in the con­trol group.

How­ev­er, in a pre­vi­ous note to investors prepar­ing them for the data, Umer Raf­fat, a biotech ana­lyst at Ever­core ISI, had said to expect the oppo­site arrange­ment: that a haz­ard ratio of 1.2 would show patients were doing bet­ter. It is not cer­tain how the haz­ard ratio is being described in the abstract.

Whether or not the drug ben­e­fit is trend­ing in a pos­i­tive or neg­a­tive direc­tion, the dif­fer­ence described in the abstract is not sta­tis­ti­cal­ly sig­nif­i­cant, mean­ing that the study failed.

There are dif­fer­ences in the enroll­ment cri­te­ria of Covid-19 patients and the way remde­sivir is being used that make extrap­o­lat­ing results from this Chi­na study to the ongo­ing stud­ies dif­fi­cult. . . .

7. A Mot­ley Fool arti­cle tries to answer the ques­tion of whether or not it’s fea­si­ble for Gilead to increase drug pro­duc­tion at suf­fi­cient lev­els,  assum­ing the drug is even­tu­al­ly proven to be effec­tive. As the arti­cle describes it, there’s no real­is­tic way Gilead can increase pro­duc­tion of the drug to meet imme­di­ate need. 

IF remde­sivir does end up being approved for COVID-19 treat­ment,  lack of ade­quate sup­ply could help Gilead prof­it con­sid­er­ably from remde­sivir. The com­pa­ny could charge even more for the drug, lim­it­ing it large­ly to wealthy indi­vid­u­als and coun­tries.  Opti­mism over remde­sivir is best war­rat­ed for Gilead’s share­hold­ers and the wealthy:

1. ” . . . . Com­plex chem­istry: Antivi­rals — com­mon­ly iden­ti­fied by the suf­fix “-vir” — are gen­er­al­ly very dif­fi­cult to man­u­fac­ture at scale. Pro­duc­tion process­es are hin­dered by many com­plex organ­ic chem­istry steps that must be com­plet­ed sequen­tial­ly, are accom­pa­nied by low yields, and require ultra-rare chem­i­cal inputs with very lim­it­ed glob­al sup­ply. The lat­ter might be the most impor­tant lim­it­ing fac­tor for remde­sivir pro­duc­tion. . . .”
2. ” . . . . Strict steril­i­ty require­ments: Drugs that are admin­is­tered intra­venous­ly (IV), such as remde­sivir, must be man­u­fac­tured in spe­cial­ty drug com­pound­ing facil­i­ties under strict steril­i­ty con­di­tions. The world has lim­it­ed pro­duc­tion capac­i­ty. . . .”
3. “Vol­ume: . . . . Man­u­fac­tur­ing antivi­ral drugs under nor­mal con­di­tions is dif­fi­cult enough, but the time crunch of a glob­al pan­dem­ic adds a new twist. Gilead Sci­ence will face pres­sure to man­u­fac­ture enough remde­sivir to treat tens of mil­lions of indi­vid­u­als, which might be an impos­si­ble task. . . .”
   
4. ” . . . . On paper, enzymes could be used to sig­nif­i­cant­ly increase the yield of remde­sivir while reduc­ing over­all inputs and, impor­tant­ly, reduc­ing the impor­tance of ultra-rare chem­i­cal inputs with lim­it­ed glob­al sup­ply. In real­i­ty, it would be very chal­leng­ing for Gilead Sci­ences to engi­neer enzymes spe­cif­ic to remde­sivir syn­the­sis, incor­po­rate them into new pro­duc­tion process­es, and scale those pro­duc­tion process­es in the com­pressed time­lines it faces. . . .”

“Gilead Sci­ences Races to Man­u­fac­ture Remde­sivir, but Chem­istry Has Speed Lim­its” by Maxx Chatsko; The Mot­ley Fool; 04/22/2020

The world is eager­ly await­ing results from hun­dreds of clin­i­cal tri­als search­ing for treat­ments for COVID-19, the res­pi­ra­to­ry dis­ease caused by the SARS-CoV­‑2 virus. Much like stay-at-home orders were issued to buy time for health sys­tems and med­ical sup­ply chains to pre­pare for pos­si­ble surges in hos­pi­tal admis­sions, effec­tive treat­ments would buy time for the world to devel­op and man­u­fac­ture effec­tive vac­cines.

One of most close­ly watched drug can­di­dates is remde­sivir from Gilead Sci­ences (NASDAQ:GILD). When promis­ing data leaked from an ongo­ing clin­i­cal tri­al, the phar­ma stock soared. It’s cer­tain­ly a promis­ing devel­op­ment at a time when the world could use some good news.

But prov­ing remde­sivir is a safe and effec­tive COVID-19 treat­ment (which hasn’t hap­pened yet) is only the first step. Gilead Sci­ences must secure sup­ply chains, ramp-up man­u­fac­tur­ing capac­i­ty, and dis­trib­ute the drug through­out the world. That might prove more dif­fi­cult than investors real­ize.

Could remde­sivir become an effec­tive COVID-19 treat­ment?

Per­haps. The dig­i­tal pub­li­ca­tion STAT, which pro­vides health­care news and com­men­tary, obtained a video from the Uni­ver­si­ty of Chica­go Med­i­cine dis­cussing inter­im results from an ongo­ing clin­i­cal tri­al. The cen­ter is one of many par­tic­i­pat­ing in a larg­er clin­i­cal tri­al eval­u­at­ing remde­sivir as a treat­ment for COVID-19.

The site enrolled 125 patients indi­vid­u­als with COVID-19, includ­ing 113 in severe con­di­tion, to receive dai­ly infu­sions of remde­sivir. Many of the patients had been safe­ly dis­charged from the hos­pi­tal, and only two had died at the time the com­ments were made. Severe fevers dis­si­pat­ed quick­ly, while oth­er patients have been removed from ven­ti­la­tors short­ly after start­ing ther­a­py.

Most impor­tant­ly, many patients were dis­charged from the hos­pi­tal in six days. Gilead Sci­ences has been study­ing 10-day cours­es of remde­sivir to treat COVID-19. Treat­ing patients for a short­er dura­tion could allow the com­pa­ny to stretch a very lim­it­ed sup­ply of the drug, which is like­ly to be the biggest bot­tle­neck.

What obsta­cles is Gilead Sci­ences star­ing down?

As of Jan­u­ary 2020, Gilead Sci­ences wasn’t active­ly man­u­fac­tur­ing remde­sivir because the drug can­di­date had nev­er been com­mer­cial­ized. The com­pa­ny had enough fin­ished prod­uct for 5,000 patients assum­ing a 10-day course of treat­ment.

After watch­ing a coro­n­avirus out­break put Chi­na on lock­down, Gilead Sci­ences raced to secure the rare mate­ri­als and pro­duc­tion capac­i­ty required to man­u­fac­ture the antivi­ral at scale. The biotech reduced the man­u­fac­tur­ing ramp-up time­line from a range of nine to 12 months to an esti­mat­ed six to eight months, and it’s work­ing to opti­mize the com­plex chem­istry required to man­u­fac­ture the drug can­di­date.

But there are speed lim­its:

Com­plex chem­istry: Antivi­rals — com­mon­ly iden­ti­fied by the suf­fix “-vir” — are gen­er­al­ly very dif­fi­cult to man­u­fac­ture at scale. Pro­duc­tion process­es are hin­dered by many com­plex organ­ic chem­istry steps that must be com­plet­ed sequen­tial­ly, are accom­pa­nied by low yields, and require ultra-rare chem­i­cal inputs with very lim­it­ed glob­al sup­ply. The lat­ter might be the most impor­tant lim­it­ing fac­tor for remde­sivir pro­duc­tion.

Strict steril­i­ty require­ments: Drugs that are admin­is­tered intra­venous­ly (IV), such as remde­sivir, must be man­u­fac­tured in spe­cial­ty drug com­pound­ing facil­i­ties under strict steril­i­ty con­di­tions. The world has lim­it­ed pro­duc­tion capac­i­ty.

Vol­ume: Man­u­fac­tur­ing antivi­ral drugs under nor­mal con­di­tions is dif­fi­cult enough, but the time crunch of a glob­al pan­dem­ic adds a new twist. Gilead Sci­ence will face pres­sure to man­u­fac­ture enough remde­sivir to treat tens of mil­lions of indi­vid­u­als, which might be an impos­si­ble task.

How many cours­es of treat­ment could be man­u­fac­tured?

Gilead Sci­ences has sig­nif­i­cant­ly increased the amount of remde­sivir on hand and made strides to bring future pro­duc­tion capac­i­ty online in North Amer­i­ca, Europe, and Asia. It still might not be enough to make the antivi­ral the world’s only COVID-19 treat­ment. Con­sid­er the company’s cur­rent fore­cast for pro­duc­tion based on treat­ments span­ning 10 days (the ini­tial expec­ta­tion) and five days (an end­point in new­er clin­i­cal tri­als).

This lim­it­ed sup­ply will be saved for hos­pi­tal­ized patients. Based on cur­rent­ly avail­able data, it appears that rough­ly 15% to 20% of con­firmed coro­n­avirus cas­es require hos­pi­tal­iza­tion. The real num­ber is like­ly much low­er once asymp­to­matic cas­es are fac­tored into the cal­cu­la­tion, but sci­en­tists have no way to gauge the num­ber of asymp­to­matic cas­es at this time.

For the sake of sim­ple math, the cur­rent 15% hos­pi­tal­iza­tion rate implies sev­er­al mil­lion dos­es of remde­sivir would be suf­fi­cient for every 20 mil­lion con­firmed coro­n­avirus cas­es. As of April 22, there are 2.6 mil­lion con­firmed coro­n­avirus cas­es glob­al­ly, although that low num­ber rep­re­sents lim­it­ed test­ing capac­i­ty and the pos­i­tive effects of stay-at-home orders.

…

Can any­thing reduce sup­ply pres­sures on remde­sivir?

Doc­tors are still learn­ing about COVID-19, but some of the mys­tery is begin­ning to fade. For exam­ple, emer­gency room doc­tor and intu­ba­tion instruc­tor Dr. Richard Lev­i­tan recent­ly wrote in The New York Times that mon­i­tor­ing oxy­gen lev­els, even in patients with­out breath­ing issues, can sig­nif­i­cant­ly reduce the need for inten­sive care and mechan­i­cal ven­ti­la­tion. That small change could help a lim­it­ed sup­ply of even­tu­al treat­ments go fur­ther.

Mean­while, hos­pi­tals around the world are begin­ning to test whether plas­ma from recov­ered COVID-19 patients can lim­it the sever­i­ty of dis­ease in cur­rent patients. It will become eas­i­er to har­vest plas­ma as more patients recov­er. If plas­ma ther­a­py proves effec­tive, then it will be anoth­er arrow in humanity’s quiver aimed at reduc­ing the impact of the coro­n­avirus pan­dem­ic.

Gilead Sci­ences could also make a Hail Mary invest­ment to sig­nif­i­cant­ly increase the pro­duc­tion of remde­sivir: enzymes. These are the com­plex pro­teins that pow­er all liv­ing things. Enzymes are used to speed up, clean up, and increase yields of chem­i­cal reac­tions with­in the set­tings of bio­log­i­cal cells all the way up to indus­tri­al chem­i­cal pro­duc­tion. They’ve gar­nered tremen­dous inter­est from phar­ma­ceu­ti­cal com­pa­nies man­u­fac­tur­ing antivi­rals.

For exam­ple, Mer­ck and Codex­is recent­ly pro­posed a nov­el man­u­fac­tur­ing process for the exper­i­men­tal HIV drug isla­travir, which belongs to the same class of drugs as remde­sivir. The pair engi­neered five enzymes to sim­pli­fy the com­plex organ­ic chem­istry required to pro­duce isla­travir. In the end, time-con­sum­ing purifi­ca­tion steps were elim­i­nat­ed, ultra-rare raw mate­ri­als were recy­cled, yields of the final drug prod­uct were sig­nif­i­cant­ly increased, and the num­ber of total pro­duc­tion process steps was reduced by more than half.

On paper, enzymes could be used to sig­nif­i­cant­ly increase the yield of remde­sivir while reduc­ing over­all inputs and, impor­tant­ly, reduc­ing the impor­tance of ultra-rare chem­i­cal inputs with lim­it­ed glob­al sup­ply. In real­i­ty, it would be very chal­leng­ing for Gilead Sci­ences to engi­neer enzymes spe­cif­ic to remde­sivir syn­the­sis, incor­po­rate them into new pro­duc­tion process­es, and scale those pro­duc­tion process­es in the com­pressed time­lines it faces.

But if there was ever a time for syn­thet­ic biol­o­gy to live up to its lofty poten­tial through a glob­al col­lab­o­ra­tive effort, now might be it. . . .

8. The remark­able han­dling of the NIAID study, the tim­ing of the announce­ment of the alto­geth­er lim­it­ed suc­cess of the atten­u­at­ed tri­al and the rise in equi­ties as a result of the announce­ment may be best under­stood in the con­text of the role played in Trump pan­dem­ic deci­sion-mak­ing by an elite group of bil­lion­aires and scientists–including con­vict­ed felon Michael Milken (the “junk bond king”).

1. ” . . . . Call­ing them­selves ‘Sci­en­tists to Stop COVID-19,’ the col­lec­tion of top researchers, bil­lion­aires and indus­try cap­tains will act as an ‘ad hoc review board’ for the tor­rent of coro­n­avirus research, ‘weed­ing out’ flawed data before it reach­es pol­i­cy­mak­ers, the Wall Street Jour­nal report­ed on Mon­day. They are also act­ing as a go-between for phar­ma­ceu­ti­cal com­pa­nies seek­ing to build a com­mu­ni­ca­tion chan­nel with Trump admin­is­tra­tion offi­cials. The group . . . . has advised Nick Ayers, an aide to Vice Pres­i­dent Mike Pence, as well as oth­er agency heads, in the past month. Pence is head­ing up the White House coro­n­avirus task force. . . .”
2. ” . . . The brainy bunch is led by Thomas Cahill, a 33-year-old doc­tor who became a ven­ture cap­i­tal­ist . . . . Cahill’s clout comes from build­ing con­nec­tions through his invest­ment firm, New­path Part­ners, with Sil­i­con Valley’s Peter Thiel, the founder of Pay­Pal, and bil­lion­aire busi­ness­men Jim Palot­ta and Michael Milken. . . .”

“Sci­en­tists, bil­lion­aires team up to aid White House in coro­n­avirus bat­tle” by Mark Moore; New York Post; 04/28/2020

A group of sci­en­tists and bil­lion­aires has joined forces to form a con­tem­po­rary “Man­hat­tan Project” designed to help the White House bat­tle the coro­n­avirus out­break, accord­ing to a report.

Call­ing them­selves “Sci­en­tists to Stop COVID-19,” the col­lec­tion of top researchers, bil­lion­aires and indus­try cap­tains will act as an “ad hoc review board” for the tor­rent of coro­n­avirus research, “weed­ing out” flawed data before it reach­es pol­i­cy­mak­ers, the Wall Street Jour­nal report­ed on Mon­day.

They are also act­ing as a go-between for phar­ma­ceu­ti­cal com­pa­nies seek­ing to build a com­mu­ni­ca­tion chan­nel with Trump admin­is­tra­tion offi­cials.

The group — who have likened their effort to the World War II-era “Man­hat­tan Project,” which devel­oped the atom­ic bomb — has advised Nick Ayers, an aide to Vice Pres­i­dent Mike Pence, as well as oth­er agency heads, in the past month.

Pence is head­ing up the White House coro­n­avirus task force.

The brainy bunch is led by Thomas Cahill, a 33-year-old doc­tor who became a ven­ture cap­i­tal­ist, and includes 2017 Nobel Prize win­ner Michael Ros­bash, a neu­ro­sci­en­tist and pro­fes­sor of biol­o­gy at Bran­deis Uni­ver­si­ty, and Stu­art Schreiber, a Har­vard chem­istry and chem­i­cal biol­o­gy pro­fes­sor.

Cahill’s clout comes from build­ing con­nec­tions through his invest­ment firm, New­path Part­ners, with Sil­i­con Valley’s Peter Thiel, the founder of Pay­Pal, and bil­lion­aire busi­ness­men Jim Palot­ta and Michael Milken.

Mem­bers of the group say they aren’t in it for finan­cial gain, but are moti­vat­ed by pro­vid­ing assis­tance for a fight that has strained fed­er­al and state gov­ern­ments, dealt a cru­cial blow to the econ­o­my and ulti­mate­ly infect­ed more than 3 mil­lion world­wide.

“We may fail,” Schreiber told the Jour­nal. “But if it suc­ceeds, it could change the world.”

The group has com­piled a 17-page plan that offers “four action­able, non-par­ti­san pro­pos­als to pro­duce safe and effec­tive COVID-19 ther­a­peu­tics and vac­cines in the short­est pos­si­ble time­frame, and to reopen our soci­ety in a man­ner that reduces the risk of future COVID-19 out­breaks,” the Wall Street Jour­nal report­ed.

Steve Pagli­u­ca, the co-own­er of the Boston Celtics, who helped copy edit some of the report, passed a copy to the CEO of Gold­man Sachs Group Inc., David Solomon, who got it to Trea­sury Sec­re­tary Steven Mnuchin.

Among the pro­pos­als are repur­pos­ing estab­lished drugs on a “great­ly accel­er­at­ed time scale” and devel­op­ing anti­bod­ies that could be used to “pro­tect healthy crit­i­cal work­ers, as well as ‘high-risk’ indi­vid­u­als.”

One of the promis­ing drugs is remde­sivir, which was devel­oped for use against Ebo­la. . . .

9. Note that Thiel played a dom­i­nant role in bankrolling New­path Part­ners, and the oth­er finan­cial angel who ele­vat­ed Cahill–Brian Sheth–introduced him to Tom­my Hicks, Jr., the co-chair­man of the RNC. In FTR #‘s 1111 and 1112, we looked at Hicks’ net­work­ing with Steve Ban­non asso­ciate J. Kyle Bass, as well as his role in the inter-agency net­works dri­ving the anti-Chi­na effort.

” . . . . At the helm of the effort: The 33-year-old and very-much-under-the-radar ven­ture cap­i­tal­ist Tom Cahill, who leads life sci­ences-focused New­path Part­ners. Cahill com­plet­ed his M.D. and PhD at Duke Uni­ver­si­ty a mere two years ago before land­ing at blue-chip invest­ment firm Rap­tor Group through a friend. He went on to found New­path with some $125 mil­lion after impress­ing well-con­nect­ed names like ven­ture cap­i­tal­ist Peter Thiel and Vista Equi­ty Part­ners co-founder Bri­an Sheth. . . . It was through Sheth, for exam­ple, that Sci­en­tists to Stop Covid-19 con­nect­ed with the co-chair­man of the Repub­li­can Nation­al Com­mit­tee, Thomas Hicks Jr. . . .”

“The ven­ture cap­i­tal­ist at the cen­ter of the coro­n­avirus fight” BY LUCINDA SHEN; For­tune; 04/28/2020

How do you get a mes­sage from lib­er­al-lean­ing sci­en­tists into a flam­ing-red White House in the mid­dle of the pan­dem­ic?

A group of sci­en­tists and bil­lion­aires that came togeth­er to fight coro­n­avirus have man­aged to do so, per a fas­ci­nat­ing read at the Wall Street Jour­nal.

Sci­en­tists to Stop Covid-19 culled togeth­er a 17-page report for offi­cials on how best to bat­tle the virus. Unlike with oth­er rec­om­men­da­tions that fade into obscu­ri­ty, gov­ern­ment agen­cies appear to be actu­al­ly read­ing and imple­ment­ing guid­ance to low­er man­u­fac­tur­ing reg­u­la­tions around spe­cif­ic coro­n­avirus drugs.

At the helm of the effort: The 33-year-old and very-much-under-the-radar ven­ture cap­i­tal­ist Tom Cahill, who leads life sci­ences-focused New­path Part­ners. Cahill com­plet­ed his M.D. and PhD at Duke Uni­ver­si­ty a mere two years ago before land­ing at blue-chip invest­ment firm Rap­tor Group through a friend. He went on to found New­path with some $125 mil­lion after impress­ing well-con­nect­ed names like ven­ture cap­i­tal­ist Peter Thiel and Vista Equi­ty Part­ners co-founder Bri­an Sheth.

As the pan­dem­ic spread, Cahill turned his atten­tion toward fight­ing Covid-19, his con­nec­tions now becom­ing his main asset in his efforts. It was through Sheth, for exam­ple, that Sci­en­tists to Stop Covid-19 con­nect­ed with the co-chair­man of the Repub­li­can Nation­al Com­mit­tee, Thomas Hicks Jr.

Cahill and his group have also been in fre­quent con­tact with Nice Ayers, a long­time aide to Vice Pres­i­dent Mike Pence. It was only fol­low­ing a call to Ayers that the FDA gave Regeneron—which need­ed to shift man­u­fac­tur­ing abroad in order to pro­duce its promis­ing coro­n­avirus treat­ment in suf­fi­cient quantities—permission to take pro­duc­tion to Dublin, per the sto­ry. . . .

10. The fed­er­al gov­ern­ments extreme focus on remde­sivir has been shaped, in large mea­sure, by the influ­ence of “Sci­en­tists to Stop COVID-19”:

1. “Sci­en­tists to Stop Covid-19” is shep­herd­ing remde­sivir: ” . . . . Sci­en­tists to Stop COVID-19 rec­om­mends that in this phase, the U.S. Food and Drug Admin­is­tra­tion (FDA) should work to coor­di­nate with Gilead phar­ma­ceu­ti­cals to focus on expe­dit­ing the results of clin­i­cal tri­als of remde­sivir, a drug iden­ti­fied as a poten­tial treat­ment for COVID-19. The group also rec­om­mends admin­is­ter­ing dos­es of the drug to patients in an ear­ly stage of infec­tion, and notes remde­sivir will essen­tial­ly be a place­hold­er until a more effec­tive treat­ment is pro­duced.
2. The group is doing so by atten­u­at­ing the reg­u­la­to­ry process for coro­n­avirus drugs: “Gov­ern­ment enti­ties and agen­cies appear to adhere to the rec­om­men­da­tions out­lined by the group, with the Jour­nal report­ing that the FDA and the Depart­ment of Vet­er­ans Affairs (VA) have imple­ment­ed some of the sug­ges­tions, name­ly relax­ing drug man­u­fac­tur­er reg­u­la­tions and require­ments for poten­tial coro­n­avirus treat­ment drugs. . . .”

“Elite group of sci­en­tists and bil­lion­aires are work­ing togeth­er to fight the coro­n­avirus pan­dem­ic” by Alexan­dra Kel­ley; The Hill; 04/28/2020

A new Wall Street Jour­nal report chron­i­cles the for­ma­tion of a Jus­tice League-esque team of sci­en­tists, doc­tors, ven­ture cap­i­tal­ists and Nobel lau­re­ates ded­i­cat­ed to devel­op­ing a com­pre­hen­sive plan to fight the coro­n­avirus.

The group, apt­ly named Sci­en­tists to Stop COVID-19, describe them­selves as “pas­sion­ate cit­i­zen-sci­en­tists” who have devel­oped “four action­able, non-par­ti­san pro­pos­als to pro­duce safe and effec­tive COVID-19 ther­a­peu­tics and vac­cines in the short­est pos­si­ble time­frame,” per a 17-page intro­duc­to­ry doc­u­ment obtained by reporter Rob Copeland.

A ven­ture cap­i­tal­ist and physi­cian named Tom Cahill report­ed­ly orga­nized the group to help fast-track a viable treat­ment for the coro­n­avirus. His con­nec­tions in both the elite finan­cial and med­ical spheres helped him pitch the idea of a group ded­i­cat­ed to devel­op­ing research to fight the virus.

Sci­en­tists to Stop COVID-19, who have effec­tive­ly become a van­guard for coro­n­avirus research, high­light the steps the U.S. must under­take in order to safe­ly recov­er from the virus. The group envi­sions the recov­ery in waves, the first char­ac­ter­ized by the use of exist­ing drugs to gain a sol­id foothold against the virus. The sec­ond wave will fea­ture treat­ments com­posed of new anti­body drugs to neu­tral­ize the virus.

The third wave envi­sioned by the orga­ni­za­tion con­sists of long-term vac­ci­na­tions to com­bat the coro­n­avirus that will offer sea­son­al and mul­ti-year immu­ni­ty. Simul­ta­ne­ous­ly, busi­ness­es, schools and oth­er pub­lic insti­tu­tions should begin to reopen around May and June of 2020, guid­ed by symp­tom report­ing, test­ing and per­son­al pro­tec­tive gear to min­i­mize future out­breaks.

Cur­rent­ly, the U.S. is in the first wave of the plan. Sci­en­tists to Stop COVID-19 rec­om­mends that in this phase, the U.S. Food and Drug Admin­is­tra­tion (FDA) should work to coor­di­nate with Gilead phar­ma­ceu­ti­cals to focus on expe­dit­ing the results of clin­i­cal tri­als of remde­sivir, a drug iden­ti­fied as a poten­tial treat­ment for COVID-19. The group also rec­om­mends admin­is­ter­ing dos­es of the drug to patients in an ear­ly stage of infec­tion, and notes remde­sivir will essen­tial­ly be a place­hold­er until a more effec­tive treat­ment is pro­duced.

Gov­ern­ment enti­ties and agen­cies appear to adhere to the rec­om­men­da­tions out­lined by the group, with the Jour­nal report­ing that the FDA and the Depart­ment of Vet­er­ans Affairs (VA) have imple­ment­ed some of the sug­ges­tions, name­ly relax­ing drug man­u­fac­tur­er reg­u­la­tions and require­ments for poten­tial coro­n­avirus treat­ment drugs.

Sci­en­tists to Stop COVID-19’s reach and influ­ence can be attrib­uted to the pres­tige of both its mem­ber­ship and its investor base. The pow­er­ful net­work­ing these con­tacts facil­i­tat­ed even­tu­al­ly helped get the group’s report to the White House Coro­n­avirus Task Force mem­bers like Trea­sury Sec­re­tary Steven Mnuchin.

Sci­en­tists to Stop COVID-19 wrote that no one cur­rent­ly involved in the group has any direct or known indi­rect finan­cial inter­est that they stand to gain from when par­tic­i­pat­ing in research. . . .

11. We con­clude with a piece about the announce­ment of Grogan’s depar­ture.

” . . . . Gro­gan has served as the direc­tor of the White House Domes­tic Pol­i­cy Coun­cil since Feb­ru­ary 2019, over­see­ing a broad array of pol­i­cy issues includ­ing health care and reg­u­la­tion. . . . Gro­gan was one of the orig­i­nal mem­bers of the White House coro­n­avirus task force launched in late Jan­u­ary. . . . Gro­gan worked as a lob­by­ist for drug com­pa­ny Gilead Sci­ences before join­ing the Trump admin­is­tra­tion. . . .”

The depar­ture was announced in the Wall Street Jour­nal on the morn­ing of Wednes­day, April 29, the same day we got our first pub­lic reports of the NIAID clin­i­cal tri­al of remde­sivir that was pos­i­tive enough to show it short­ened the time to recov­ery and the same day the FDA grant­ed remde­sivir emer­gency use sta­tus. 

Note, again, the tim­ing of the DSM­B’s actions, as well as the imflu­ence of “Sci­en­tists to Stop Covid-19.”

“Top Trump pol­i­cy advis­er Joe Gro­gan to leave post” by Mor­gan Chal­fant; The Hill; 04/29/2020

Joe Gro­gan, head of the White House Domes­tic Pol­i­cy Coun­cil, intends to leave his posi­tion at the end of May.

A White House offi­cial con­firmed Grogan’s planned depar­ture, which was first report­ed by The Wall Street Jour­nal. Gro­gan told the Jour­nal that he was leav­ing the White House on good terms with Pres­i­dent Trump and that he planned to leave the posi­tion on May 24, hav­ing stayed in the role longer than he antic­i­pat­ed.

Grogan’s depar­ture had been rumored as a pos­si­bil­i­ty for weeks, par­tic­u­lar­ly fol­low­ing the arrival of Mark Mead­ows, a for­mer North Car­oli­na con­gress­man, as Trump’s fourth chief of staff.

“I had a great con­ver­sa­tion with the pres­i­dent and a great con­ver­sa­tion with Mead­ows,” Gro­gan told the Jour­nal in an inter­view pub­lished Wednes­day evening.

Gro­gan has served as the direc­tor of the White House Domes­tic Pol­i­cy Coun­cil since Feb­ru­ary 2019, over­see­ing a broad array of pol­i­cy issues includ­ing health care and reg­u­la­tion.

Before that, he worked as a top health care offi­cial in the Office of Man­age­ment and Bud­get begin­ning in 2017 and was a close ally of Mick Mul­vaney, Trump’s third chief of staff, whom Mead­ows replaced in March. Gro­gan worked as a lob­by­ist for drug com­pa­ny Gilead Sci­ences before join­ing the Trump admin­is­tra­tion.

…

Gro­gan was one of the orig­i­nal mem­bers of the White House coro­n­avirus task force launched in late Jan­u­ary. It was not imme­di­ate­ly clear who would replace him as head of the Domes­tic Pol­i­cy Coun­cil.

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