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Covid-19 roundup: Boehringer pulls a drug out of the pipeline for a PhII Covid-19 tri­al; No­vavax de­lays PhI­II tri­al in US, with PhII da­ta com­ing Fri­day

With big ques­tions still hang­ing over the fate of the vac­cines and drugs now in late-stage de­vel­op­ment for Covid-19, Boehringer In­gel­heim is pulling one of its ear­ly-stage drugs in­to a Phase II tri­al to see if it can help some of the most se­vere­ly af­flict­ed pa­tients.

Put through a safe­ty study last year, re­searchers have been in­trigued by the po­ten­tial of BI 764198 — a TR­PC6 in­hibitor — as a treat­ment for acute res­pi­ra­to­ry dis­tress syn­drome (ARDS), which can cause im­mense dam­age and death for pa­tients ex­posed to the virus.

Clive Wood

As the pan­dem­ic hit, “we start­ed to ask, what are the mech­a­nisms we have in the pipeline, what might help these pa­tients?” says Clive Wood, head of dis­cov­ery re­search at Boehringer. That led them to a drug in de­vel­op­ment for chron­ic kid­ney dis­ease, which shares a path­way that could have an im­pact on the virus.

“We are far from hav­ing a clear path to hav­ing a clear path to the end of this sit­u­a­tion,” says Wood, and that makes it im­por­tant to re­cruit 90 pa­tients for the Phase II, with the abil­i­ty to piv­ot in­to a late-stage reg­is­tra­tion study if it works out.

Even if it doesn’t work out in time for Covid-19, Boehringer’s re­searchers ex­pect that suc­cess could pave the way to oth­er us­es in the fu­ture. Right now, the on­ly thing they know for cer­tain is they need to see if it works. — John Car­roll

Man­u­fac­tur­ing de­lay push­es back the launch of a PhI­II at No­vavax

Though No­vavax $NVAX is near the fore­front of the Covid-19 vac­cine race, it will be start­ing its Phase III tri­al lat­er than an­tic­i­pat­ed.

The com­pa­ny said Tues­day that its late-stage study in the US has been pushed back to the end of No­vem­ber af­ter de­lays in up­scal­ing its man­u­fac­tur­ing process­es. That’s about one month af­ter pre­vi­ous­ly re­port­ed time­lines.

Mean­while, tri­al da­ta from a sep­a­rate Phase III be­ing con­duct­ed in the UK are like­ly com­ing some­time “ear­ly” in the first quar­ter, No­vavax said, adding that the re­sults from this study “are ex­pect­ed to serve as the ba­sis for glob­al li­cen­sure.” No­vavax did not elab­o­rate on what that meant nor how they plan to ap­ply for such “li­cen­sure” in the US.

Ad­di­tion­al­ly, new Phase II da­ta from the com­pa­ny’s on­go­ing Phase I/II tri­al are ex­pect­ed to come Fri­day. In­vestors most­ly greet­ed the news warm­ly, as the com­pa­ny’s shares rose about 3% in Tues­day trad­ing.

While there haven’t been any Covid-19 vac­cine ap­provals or EUAs thus far, there have been a few for treat­ments. The FDA re­cent­ly grant­ed ap­proval for Gilead’s remde­sivir, mar­ket­ed as Vek­lury, in hos­pi­tal­ized pa­tients old­er than 12. That fol­lowed an EUA for the ther­a­py, as well as EUAs for hy­drox­y­chloro­quine and con­va­les­cent plas­ma. Reg­u­la­tors have since re­voked the for­mer’s au­tho­riza­tion.

No­vavax re­ceived a $1.6 bil­lion Warp Speed con­tract in Ju­ly and be­gan its UK Phase III study in late Sep­tem­ber. The biotech is test­ing a two-shot reg­i­men of its low­er, 5 µg dose of pro­tein anti­gen cur­rent­ly in Phase II, plus a 50 µg Ma­trix‑M ad­ju­vant. The shots are be­ing ad­min­is­tered 21 days apart.

Pfiz­er cur­rent­ly leads End­points News’ Covid-19 vac­cine race track­er, with No­vavax com­ing in 8th. — Max Gel­man

CBER di­rec­tor promis­es ‘safe and ef­fec­tive’ vac­cine in op-ed

In an ef­fort to shore up trust in the FDA’s abil­i­ty to au­tho­rize a safe and ef­fec­tive vac­cine, CBER di­rec­tor Pe­ter Marks broke down the EUA process in a USA To­day op-ed. 

“We hope to en­sure pub­lic con­fi­dence in COVID-19 vac­cines by be­ing trans­par­ent about FDA’s de­ci­sion-mak­ing process,” he wrote. “Whether a vac­cine is made avail­able through an EUA or through a tra­di­tion­al ap­proval, FDA will en­sure that it is safe and ef­fec­tive.”

Pe­ter Marks

In the rough­ly 1,000-word piece, Marks promised that an EUA de­ci­sion will not be rushed. And he ex­plained that the FDA’s min­i­mum rec­om­men­da­tion of 50% ef­fi­ca­cy is just that — a min­i­mum.

“Of course, it is hoped that the vac­cines will pre­vent a much high­er per­cent­age of cas­es, but the 50% fig­ure es­tab­lish­es the min­i­mum ef­fi­ca­cy of a COVID-19 vac­cine that FDA could find ac­cept­able,” he said.

The di­rec­tor al­so men­tioned that con­sid­er­a­tions for an EUA may be dif­fer­ent, de­pend­ing on how a prod­uct will be used. For ex­am­ple, if a drug is in­tend­ed for hos­pi­tal­ized pa­tients who have no oth­er treat­ment, “the po­ten­tial ben­e­fits may out­weigh the risks even if there is un­cer­tain­ty about ef­fec­tive­ness and there are re­al, but ac­cept­able, safe­ty con­cerns,” Marks wrote.

In June, the FDA yanked an EUA for hy­drox­y­chloro­quine as a Covid-19 treat­ment, af­ter de­ter­min­ing the drug is “un­like­ly to be ef­fec­tive.” And in Sep­tem­ber, a pan­el of ex­perts con­vened by the NIH con­clud­ed that there is a lack of da­ta sup­port­ing the safe­ty and ef­fi­ca­cy of an­oth­er coro­n­avirus treat­ment grant­ed an EUA: con­va­les­cent plas­ma.

In the op-ed, Marks said that wouldn’t be the case for a vac­cine:

For a COVID-19 vac­cine that could be ad­min­is­tered to mil­lions of in­di­vid­u­als, in­clud­ing healthy peo­ple, FDA will on­ly is­sue an EUA if a vac­cine has demon­strat­ed clear and com­pelling ef­fi­ca­cy in a large well-de­signed phase 3 clin­i­cal tri­al, much like would be re­quired for a BLA. 

Nor­mal­ly, drug mak­ers take months to an­a­lyze da­ta be­fore sub­mit­ting a BLA, which can be tens of thou­sands of pages long, ac­cord­ing to Marks. “But these are not ‘nor­mal’ times,” he said. “In the Unit­ed States, we have seen many hun­dreds of peo­ple die every day from COVID-19.”

“With high up­take, COVID-19 vac­cines have the po­ten­tial to save many lives in the Unit­ed States that may oth­er­wise be lost. And sav­ing as many lives as is pos­si­ble must be the goal that we strive to achieve to­geth­er,” he wrote. — Nicole De­Feud­is

Sanofi and GSK pledge 200 mil­lion vac­cine dos­es

Sanofi and GSK have agreed to give 200 mil­lion dos­es of their vac­cine can­di­date to the CO­V­AX Fa­cil­i­ty, which is part of a pro­gram set up by CEPI, the WHO and Gavi to eq­ui­tably dis­trib­ute vac­cines around the world.

The idea be­hind CO­V­AX is to give all par­tic­i­pat­ing coun­tries equal ac­cess to vac­cines, re­gard­less of in­come lev­el. As of Oct. 14, more than 180 coun­tries had signed agree­ments to the CO­V­AX Fa­cil­i­ty, in­clud­ing France and the UK. Chi­na joined ear­li­er this month, pledg­ing to make its vac­cines a “glob­al pub­lic good.” One coun­try no­tably off the list is the Unit­ed States.

The Trump ad­min­is­tra­tion has re­fused to join the pro­gram. The US has placed an ini­tial $1.95 bil­lion or­der for 100 mil­lion dos­es of Pfiz­er’s can­di­date, with the op­tion to ac­quire up to 500 mil­lion more down the road. And it placed a $1.5 bil­lion or­der with Mod­er­na for 100 mil­lion dos­es, with an op­tion for an­oth­er 400 mil­lion lat­er. One White House spokesman said the coun­try won’t be “con­strained by mul­ti­lat­er­al or­ga­ni­za­tions in­flu­enced by the cor­rupt World Health Or­ga­ni­za­tion and Chi­na,” ac­cord­ing to a Bloomberg re­port.

CO­V­AX is hop­ing to have 2 bil­lion dos­es avail­able by the end of 2021, “which should be enough to pro­tect high risk and vul­ner­a­ble peo­ple, as well as front­line health­care work­ers,” the GAVI web­site states.

Thomas Tri­om­phe

Sanofi and GSK en­tered their ad­ju­vant­ed re­com­bi­nant pro­tein-based can­di­date in a Phase I/II study on Sept. 3, and an­tic­i­pate the first cut of da­ta in ear­ly De­cem­ber. The com­pa­nies are hop­ing the re­sults sup­port the launch a piv­otal Phase III tri­al be­fore the end of the year. If all goes ac­cord­ing to plan, they think a re­quest for ap­proval could come in the first half of 2021.

“The com­mit­ment we are an­nounc­ing to­day for the CO­V­AX Fa­cil­i­ty can help us to­geth­er stand a bet­ter chance of bring­ing the pan­dem­ic un­der con­trol,” Sanofi Pas­teur ex­ec­u­tive VP and glob­al head Thomas Tri­om­phe said in a state­ment. “This mo­ment al­so re­flects our long-term com­mit­ment to glob­al health and en­sures our COVID-19 vac­cines are af­ford­able and ac­ces­si­ble to those most at risk, every­where in the world.” — Nicole De­Feud­is

Vac­ci­nol­o­gist Paul Of­fit calls for more ef­fi­ca­cy da­ta 

In the next cou­ple months, drug mak­ers will like­ly sub­mit EUA ap­pli­ca­tions for Covid-19 vac­cines, renowned vac­ci­nol­o­gist Paul Of­fit pre­dicts.

This could come at the be­gin­ning of a “twindem­ic” — par­al­lel flu and coro­n­avirus out­breaks, he added. The ques­tion is, what will be re­quired for emer­gency au­tho­riza­tion?

“Per­mis­sion is be­ing giv­en to vac­ci­nate 150 mil­lion Amer­i­cans es­sen­tial­ly, which is ob­vi­ous­ly some­thing we’ve nev­er dealt with be­fore,” Of­fit, di­rec­tor of the Chil­dren’s Hos­pi­tal of Philadel­phia’s Vac­cine Ed­u­ca­tion Cen­ter and in­ven­tor of the ro­tavirus vac­cine, said in a JA­MA Net­work in­ter­view.

Paul Of­fit

“How much un­cer­tain­ty are we will­ing to live with know­ing that we’re fac­ing a virus that’s brought us to our knees?” he asked lat­er.

Of­fit said he’s con­cerned the pub­lic will see emer­gency au­tho­riza­tion as “flim­sy,” or based on a lack of ev­i­dence, af­ter what hap­pened with hy­drox­y­chloro­quine and the “con­va­les­cent plas­ma fi­as­co.”

“I think where the rub­ber’s go­ing to meet the road here is how we han­dle these in­ter­im analy­ses,” he said in the in­ter­view.

Pfiz­er and BioN­Tech, cur­rent­ly in the lead for an EUA, an­nounced in their tri­al pro­to­col that their first in­ter­im analy­sis would oc­cur when 32 par­tic­i­pants are in­fect­ed. Mod­er­na will hold its first in­ter­im analy­sis at 53 events. And As­traZeneca is plan­ning to con­duct an analy­sis when 75 pa­tients get sick. Re­searchers would then com­pare how many in­fec­tions oc­curred in the vac­cine arm, ver­sus the place­bo arm.

“I’d like to think that we’re go­ing to be re­al­ly loathe to ap­prove this or to rec­om­mend ap­proval through emer­gency use au­tho­riza­tion with just 34 or 60 par­tic­i­pants get­ting sick,” Of­fit said.

In NIH AC­TIV tri­als, sta­tis­ti­cians want­ed to see 147 in­fec­tions if the vac­cine was ad­min­is­tered in a 2:1 ra­tio to place­bo, or 160 in­fec­tions in a 1:1 sce­nario, Of­fit said. “That’s where I’m com­ing from,” he added.

“If dreams could come true, all I ask is this: Let’s have at least 150 par­tic­i­pants that got sick,” Of­fit said. “That’s all I ask.” — Nicole De­Feud­is

Im­ple­ment­ing re­silience in the clin­i­cal tri­al sup­ply chain

Since January 2020, the clinical trials ecosystem has quickly evolved to manage roadblocks impeding clinical trial integrity, and patient care and safety amid a global pandemic. Closed borders, reduced air traffic and delayed or canceled flights disrupted global distribution, revealing how flexible logistics and supply chains can secure the timely delivery of clinical drug products and therapies to sites and patients.

In fi­nal days at Mer­ck, Roger Perl­mut­ter bets big on a lit­tle-known Covid-19 treat­ment

Roger Perlmutter is spending his last days at Merck, well, spending.

Two weeks after snapping up the antibody-drug conjugate biotech VelosBio for $2.75 billion, Merck announced today that it had purchased OncoImmune and its experimental Covid-19 drug for $425 million. The drug, known as CD24Fc, appeared to reduce the risk of respiratory failure or death in severe Covid-19 patients by 50% in a 203-person Phase III trial, OncoImmune said in September.

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Pascal Soriot (AP Images)

UP­DAT­ED: As­traZeneca, Ox­ford on the de­fen­sive as skep­tics dis­miss 70% av­er­age ef­fi­ca­cy for Covid-19 vac­cine

On the third straight Monday that the world wakes up to positive vaccine news, AstraZeneca and Oxford are declaring a new Phase III milestone in the fight against the pandemic. Not everyone is convinced they will play a big part, though.

With an average efficacy of 70%, the headline number struck analysts as less impressive than the 95% and 94.5% protection that Pfizer/BioNTech and Moderna have boasted in the past two weeks, respectively. But the British partners say they have several other bright spots going for their candidate. One of the two dosing regimens tested in Phase III showed a better profile, bringing efficacy up to 90%; the adenovirus vector-based vaccine requires minimal refrigeration, which may mean easier distribution; and AstraZeneca has pledged to sell it at a fraction of the price that the other two vaccine developers are charging.

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Bob Nelsen (Photo by Michael Kovac/Getty Images)

Bob Nelsen rais­es $800M and re­cruits a star-stud­ded board to build the 'Fox­con­n' of biotech

Bob Nelsen spent his pandemic spring in his Seattle home, talking on the phone with Luciana Borio, the scientist who used to run pandemic preparedness on the National Security Council, and fuming with her about the dire state of American manufacturing.

Companies were rushing to develop vaccines and antibodies for the new virus, but even if they succeeded, there was no immediate supply chain or infrastructure to mass-produce them in a way that could make a dent in the outbreak.

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Leonard Schleifer, Regeneron CEO (Andrew Harnik/AP)

Trail­ing Eli Lil­ly by 12 days, Re­gen­eron gets the FDA OK for their Covid-19 an­ti­body cock­tail

A month and a half after becoming the experimental treatment of choice for a newly diagnosed president, Regeneron’s antibody cocktail has received emergency use authorization from the FDA. It will be used to treat non-hospitalized Covid-19 patients who are at high-risk of progressing.

Although the Rgeneron drug is not the first antibody treatment authorized by the FDA, the news comes as a significant milestone for a company and a treatment scientists have watched closely since the outbreak began.

Am­gen sev­ers 14-year Cy­to­ki­net­ics part­ner­ship, bail­ing on ome­cam­tiv af­ter mixed PhI­II re­sults

Amgen is shrugging off a 14-year development alliance and the tens of millions of dollars spent to develop a new heart drug at Cytokinetics after a Phase III trial turned up weak data — leaving Cytokinetics to soldier on alone.

Omecamtiv mecarbil technically worked, meeting the primary composite endpoint in the Phase III GALACTIC-HF study. But it missed a key secondary endpoint, which analysts had been following as a key marker for success — reduction of cardiovascular (CV) death. While Cytokinetics celebrated the results, its stock tanked 43% upon the news, and analysts warned of an uncertain path ahead. Now, Amgen wants out.

News brief­ing: Ab­b­Vie part­ner Teneo­bio ex­pands tech li­cense with CAR-T play­er Po­sei­da; Ar­genx buys PRV from Bay­er for $98M

Teneobio may be best known for its pact with AbbVie and Gilead, but before its big break the bispecific player had licensed its antibodies for a different use: as binders in CAR-T therapies being developed by Poseida.

Now, the biotechs are expanding their partnership, with Poseida exercising four options to deploy Teneobio’s heavy chain only domain antibodies commercially.

The commercial licensing fees remained under wraps, but Teneobio is eligible for $250 million in milestones for these CAR-Ts against undisclosed targets.

Carl Hansen, AbCellera CEO (University of British Columbia)

From a pair of Air Jor­dans to a $200M-plus IPO, Carl Hansen is craft­ing an overnight R&D for­tune fu­eled by Covid-19

Back in the summer of 2019, Carl Hansen left his post as a professor at the University of British Columbia to go full time as the CEO at a low-profile antibody shop he had founded called AbCellera.

As biotech CEOs go, even after a fundraise Hansen wasn’t paid a whole heck of a lot. He ended up earning right at $250,000 for the year. His compensation package included a loan — which he later paid back — and a pair of Air Jordan tennis shoes. His newly-hired CFO, Andrew Booth, got a sweeter pay packet than that — which included his own pair of Air Jordans.

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Bahija Jallal (file photo)

TCR pi­o­neer Im­muno­core scores a first with a land­mark PhI­II snap­shot on over­all sur­vival for a rare melanoma

Bahija Jallal’s crew at TCR pioneer Immunocore says they have nailed down a promising set of pivotal data for their lead drug in a frontline setting for a solid tumor. And they are framing this early interim readout as the convincing snapshot they need to prove that their platform can deliver on a string of breakthrough therapies now in the clinic or planned for it.

In advance of the Monday announcement, Jallal and R&D chief David Berman took some time to walk me through the first round of Phase III data for their lead TCR designed to treat rare, frontline cases of metastatic uveal melanoma that come with a grim set of survival expectations.

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