Scott Gottlieb (Getty Images)

Covid-19 roundup: FDA com­mis­sion­ers call for more ‘con­cert­ed ef­fort’ on con­va­les­cent plas­ma R&D; Re­gen­eron boosts case for an­ti­body cock­tail with new an­i­mal da­ta

Four for­mer FDA com­mis­sion­ers have co­a­lesced around a cen­tu­ry-old treat­ment they be­lieve can give the best weapon against Covid-19: Con­va­les­cent plas­ma.

Writ­ing in The Wash­ing­ton Postfor­mer FDA com­mis­sion­ers Mark Mc­Clel­lan, Mar­garet Ham­burg, Robert Califf and Scott Got­tlieb said that while more work needs to be done to prove it’s safe and ef­fec­tive, con­va­les­cent plas­ma was a “promis­ing treat­ment” that “could help mil­lions of pa­tients with the nov­el coro­n­avirus both here and abroad.” They warned, though, that for it to be­come an ef­fec­tive tool in the US’ Covid-19 re­sponse, a more “con­cert­ed ef­fort” is need­ed to re­cruit donors and run tri­als.

“But if this is go­ing to work, we need to do it right,“ they wrote.

The for­mer FDA com­mis­sion­ers are hard­ly the first to call for a fo­cus on plas­ma. The ap­proach has been used to com­bat vi­ral and bac­te­r­i­al out­breaks since be­fore the Span­ish flu and Chi­nese re­searchers turned to it to treat coro­n­avirus pa­tients as ear­ly as Jan­u­ary. In March, amid ef­forts by re­searchers at Johns Hop­kins, the FDA gave emer­gency clear­ance both to start con­va­les­cent plas­ma tri­als and to give out the ther­a­py un­der emer­gency use. Pres­i­dent Trump pro­mot­ed the ther­a­py at the Amer­i­can Red Cross last week. It in­volves tak­ing an­ti­body-rich serum from the blood of pa­tients who have re­cov­ered from Covid-19 and trans­fer­ring it to new­ly in­fect­ed pa­tients to boost their im­mune re­sponse.

The ex-com­mis­sion­ers, though, called for those ef­forts to be more di­rect­ed. So far, over 40,000 Amer­i­cans have re­ceived plas­ma through a joint pro­gram be­tween HHS and the Mayo Clin­ic, yet there still has yet to be a large ran­dom­ized tri­al to de­ter­mine if the ther­a­py works and on which pa­tients. The for­mer com­mis­sion­ers com­pared the cur­rent sit­u­a­tion to the one doc­tors faced in the spring with hy­drox­y­chloro­quine, where there was a the­o­ry for why it should work but lit­tle da­ta.

“Thou­sands of covid-19 pa­tients have been treat­ed with plas­ma, but we are not much clos­er to de­fin­i­tive­ly an­swer­ing those ques­tions,” they wrote.

The com­mis­sion­ers not­ed, though, that ef­forts were un­der­way. They tout­ed the work of The Fight Is In Us, coali­tion that is en­cour­ag­ing more peo­ple to do­nate their plas­ma.

Some of those ef­forts are al­ready un­der­way. The NIH is about to start tri­als test­ing plas­ma, along with mon­o­clon­al an­ti­bod­ies. And Johns Hop­kins re­ceived $35 mil­lion last week from the DoD for na­tion­wide clin­i­cal tri­als. The com­mis­sion­ers not­ed, though, that on­ly a small frac­tion of Covid-19 pa­tients can en­ter those tri­als. They called for larg­er, co­or­di­nat­ed stud­ies, cit­ing as an ex­am­ple the UK Re­cov­ery stud­ies that showed hy­drox­y­chloro­quine didn’t work and the steroid dex­am­etha­sone did.

“We can’t waste pre­cious time and put peo­ple at risk by treat­ing them with ther­a­pies that don’t work or miss op­por­tu­ni­ties to col­lect da­ta and de­ter­mine when a treat­ment is ben­e­fi­cial,” they wrote. — Ja­son Mast

Re­gen­eron posts an­i­mal da­ta, rais­ing hopes for an­ti­bod­ies as both pro­phy­lac­tic and treat­ment

New da­ta from an­i­mal stud­ies of Re­gen­eron’s an­ti­body cock­tail sug­gest it can both pre­vent and treat Covid-19, boost­ing the com­pa­ny’s case as it moves through Phase II/III pro­grams.

The find­ings in rhe­sus macaques and ham­sters — which have not been peer re­viewed — al­so echo pre­dic­tions by ex-FDA com­mis­sion­er Scott Got­tlieb and Lu­ciana Bo­rio, the for­mer di­rec­tor of med­ical and biode­fense pre­pared­ness at the Na­tion­al Se­cu­ri­ty Coun­cil, that an­ti­bod­ies will be the bridge to a vac­cine.

Not on­ly did the an­ti­bod­ies low­er vi­ral load in the an­i­mals, they al­so re­duced virus in­duced pathol­o­gy. Re­gen­eron sci­en­tists aren’t shy about stress­ing the sig­nif­i­cance here.

“The abil­i­ty of REGN-COV2 to al­most com­plete­ly block de­tec­tion of subge­nom­ic species of SARS-COV-2 RNA match­es or ex­ceeds the ef­fects re­cent­ly shown in vac­cine ef­fi­ca­cy stud­ies us­ing the same an­i­mal mod­els,” the team, led by Chris­tos Kyrat­sous, wrote. “Ad­di­tion­al­ly, the ob­served ac­cel­er­at­ed re­duc­tion of up­per air­way virus load in rhe­sus macaques treat­ed with REGN-COV2 con­trasts the lack of im­pact on vi­ral load in remde­sivir treat­ed an­i­mals, where re­duced vi­ral load could on­ly be ob­served in low­er air­ways with no dif­fer­ences in nasal vi­ral RNA lev­els.”

In the study, rhe­sus macaques served as a mod­el for tran­sient and mild dis­ease while the gold­en ham­ster typ­i­cal­ly man­i­fests a much more se­vere form ac­com­pa­nied by rapid weight loss and se­vere lung in­jury, the re­searchers wrote. For the pro­phy­lac­tic set­ting, they test­ed two dos­es (50 mg/kg and 0.3 mg/kg) and ex­posed the an­i­mals to the virus 3 days af­ter an­ti­body ad­min­is­tra­tion.

When armed with the an­ti­bod­ies, which bind to dif­fer­ent epi­topes on the coro­n­avirus spike pro­tein, the an­i­mals were able to with­stand even a high­er vi­ral chal­lenge.

Com­pared to place­bo, REGN-COV2 al­so helped an­i­mals clear the virus faster when giv­en one day post-in­fec­tion. Then there’s the clean safe­ty pro­file, with no ev­i­dence of an­ti­body-me­di­at­ed en­hance­ment of dis­ease.

All of this points to the po­ten­tial of clin­i­cal ben­e­fit, and Re­gen­eron doesn’t have to wait long to con­firm it. A tri­al in­volv­ing non-hos­pi­tal­ized pa­tients is slat­ed for com­ple­tion in No­vem­ber and the study for hos­pi­tal­ized pa­tients will wrap next Jan­u­ary, but the first cut of da­ta could al­ways emerge ear­li­er.

In an ide­al sce­nario, the da­ta will sup­port an emer­gency use au­tho­riza­tion, at which point Re­gen­eron will have tens to hun­dreds of thou­sands of dos­es lined up. Hav­ing nabbed the first ther­a­peu­tic con­tract from Op­er­a­tion Warp Speed to­tal­ing $450 mil­lion, the biotech has been ramp­ing up its man­u­fac­tur­ing to de­liv­er an es­ti­mat­ed 70,000 to 300,000 treat­ment dos­es and around 420,000 to 1.3 mil­lion pre­ven­tion dos­es as ear­ly as late sum­mer. — Am­ber Tong

DoD shines a spot­light on GM-CSF, of­fer­ing $35M to bankroll PhII stud­ies 

GM-CSF, or gran­u­lo­cyte macrophage-colony stim­u­lat­ing fac­tor, is emerg­ing as the next tar­get for drug re­pur­pos­ing af­ter a slate of IL-6 ther­a­pies sput­tered out.

Lex­ing­ton, MA-based Part­ner Ther­a­peu­tics has se­cured a $35 mil­lion con­tract with the US De­part­ment of De­fense to test its in­haled re­com­bi­nant GM-CSF, Leukine, for Covid-19 pa­tients who ex­pe­ri­ence acute hy­pox­emia.

The biotech plans to launch the first of two Phase stud­ies in Au­gust 2020, eval­u­at­ing the drug in treat­ing Covid-19 as­so­ci­at­ed acute hy­pox­emic res­pi­ra­to­ry fail­ure, with oxy­gena­tion and per­cent of pa­tients in­tu­bat­ed as the key met­rics. The fund­ing will al­so sup­port reg­u­la­to­ry fil­ings and ex­pan­sion of pro­duc­tion ca­pac­i­ty.

These new da­ta will sup­ple­ment re­sults from more than 60 pa­tients who have been en­rolled in a tri­al PTx is con­duct­ing in Bel­gium.

“GM-CSF is es­sen­tial for lung health. Emerg­ing da­ta sug­gest that COVID-19 is as­so­ci­at­ed with im­mune dys­func­tion in­clud­ing de­fi­cien­cy of alve­o­lar macrophages and GM-CSF,” said De­ba­sish Roy­chowd­hury, chief med­ical of­fi­cer at PTx. “Treat­ment with Leukine may con­fer ben­e­fit to pa­tients with acute res­pi­ra­to­ry dis­tress and po­ten­tial­ly re­duce long term com­pli­ca­tions.”

Glax­o­SmithK­line brought some at­ten­tion to the tar­get when the phar­ma gi­ant an­nounced in May that it would test its rheuma­toid arthri­tis drug otil­imab for Covid-19, with a goal to block a key cy­tokine and ease the ef­fect of an in­fec­tion on the lungs. The NIH lent more cre­dence to the con­cept re­cent­ly by adding Hu­mani­gen’s lenzilum­ab to a mas­ter pro­to­col com­par­ing a com­bo with remde­sivir to remde­sivir alone. — Am­ber Tong

For a look at all End­points News coro­n­avirus sto­ries, check out our spe­cial news chan­nel.

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

President Donald Trump (via AP Images)

Signs of an 'Oc­to­ber Vac­cine Sur­prise' alarm ca­reer sci­en­tists

President Donald Trump, who seems intent on announcing a COVID-19 vaccine before Election Day, could legally authorize a vaccine over the objections of experts, officials at the FDA and even vaccine manufacturers, who have pledged not to release any vaccine unless it’s proved safe and effective.

In podcasts, public forums, social media and medical journals, a growing number of prominent health leaders say they fear that Trump — who has repeatedly signaled his desire for the swift approval of a vaccine and his displeasure with perceived delays at the FDA — will take matters into his own hands, running roughshod over the usual regulatory process.

Anthony Fauci (AP Images)

A press of­fi­cer at An­tho­ny Fau­ci’s NI­AID was un­masked as a hard-right Covid troll. He just re­tired to­day

William B Crews had been a public affairs specialist at the NIH’s National Institute of Allergy and Infectious Diseases.

That ended today when he informed the agency of his decision to retire, after he was identified as the managing editor at RedState, a prominent Trump loyalist website.

Crews’ RedState duties are performed under the alias streiff. While enjoying the benefits of pseudonymity, he disparaged and worked against NIAID with an incendiary level of rhetoric in the midst of a pandemic.

#ES­MO20: Push­ing in­to front­line, Mer­ck and Bris­tol My­ers duke it out with new slate of GI can­cer da­ta

Having worked in parallel for years to move their respective PD-1 inhibitors up to the first-line treatment of gastrointestinal cancers, Merck and Bristol Myers Squibb finally have the data at ESMO for a showdown.

Comparing KEYNOTE-590 and CheckMate-649, of course, comes with the usual caveats. But a side-by-side look at the overall survival numbers also offer some perspective on a new frontier for the reigning checkpoint rivals, both of whom are claiming to have achieved a first.

Donald Trump, AP

Covid-19 roundup: Trump sug­gests Pfiz­er vac­cine could be first ap­proved; VBI Vac­cines inks de­vel­op­ment deal with Cana­da

President Donald Trump commented Monday morning that Pfizer’s Covid-19 vaccine candidate could be the first to win approval by regulators.

During an interview on a Fox News’ morning show, the president said Pfizer was doing “very well” when asked which candidate could be approved, according to a Reuters report. He added that J&J could follow up afterward, saying “they’ll probably be a little later.”

UP­DAT­ED: Two wild weeks for Grail end in $8B Il­lu­mi­na buy­out

Grail’s whirlwind two weeks have ended in the wealthy arms of its former founder and benefactors.

Illumina has shelled out $8 billion to reacquire the closely-watched liquid biopsy startup they spun out just 5 years ago and sold off much of its shares just 3 years ago. The deal comes nearly two weeks after the well-heeled startup filed for a potentially massive IPO — one that was disrupted just a week later when Bloomberg reported that Illumina was in talks to buy their former spinout for up to $8 billion.

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As­traZeneca pub­lish­es Covid-19 vac­cine PhI­II pro­to­cols in lock­step with Mod­er­na and Pfiz­er. How are they dif­fer­ent?

Following in the steps of Moderna and Pfizer, the other two American drugmakers currently in Phase III trials for their Covid-19 vaccines, AstraZeneca posted its own study protocols over the weekend. The move is the latest in a series of rare peeks behind the curtain, as such blueprints are typically shared once such trials are completed.

“Given the unprecedented global impact of the Coronavirus pandemic and the need for public information, AstraZeneca has published the detailed protocol and design of our AZD1222 clinical trial. As with most clinical development, protocols are not typically shared publicly due to the importance of maintaining confidentiality and integrity of trials. AstraZeneca continues to work with industry peers to ensure a consistent approach to sharing timely clinical trial information,” the company said in a statement.

Roche vaults to the front of the NL­RP3 clin­i­cal race, pay­ing $448M up­front to bag In­fla­zome

Roche is going all in on NLRP3.

The pharma giant is putting down $448 million (€380 million) upfront to snatch Novartis-backed Inflazome, which makes it a clinical player in the space overnight.

Dublin and Cambridge, UK-based Inflazome is the second NLRP3-focused biotech Roche has acquired in less than two years, and although no numbers were disclosed in the Jecure buyout, this is almost certainly a much larger deal.

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Eli Lilly CSO Dan Skovronsky (file photo)

UP­DAT­ED: #ES­MO20: Eli Lil­ly shows off the da­ta for its Verzenio suc­cess. Was it worth $18 bil­lion?

The press release alone, devoid of any number except for the size of the trial, added nearly $20 billion to Eli Lilly’s market cap back in June. Now investors and oncologists will get to see if the data live up to the hype.

On Sunday at ESMO, Eli Lilly announced the full results for its Phase III MonarchE trial of Verzenio, showing that across over 5,000 women who had had HR+, HER2- breast cancer, the drug reduced the odds of recurrence by 25%. That meant 7.8% of the patients on the drug arm saw their cancers return within 2 years, compared with 11.3% on the placebo arm.

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