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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

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Who’s spend­ing and who’s cut­ting from Big Phar­ma’s $127B R&D bud­get? Here are the top 15 play­ers

A couple of the Big 15 biopharma companies in R&D hit the gas on research spending last year. Merck and Sanofi still have lots to prove in the pipeline, and they’re willing to gamble large sums to make a better future for themselves.

Doing nothing would be infinitely worse.

But collectively, the top players rang up a modest 2.4% increase in spending in 2022, which didn’t cover inflationary pressures. And that set the tone for an extraordinarily cautious year for the industry — even as it laid out about $127 billion to advance new drugs or up the ante on approved therapies.

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Jeff Bluestone (R), Sonoma Biotherapeutics CEO

Jef­frey Blue­stone brings his start­up haul to $400M+, join­ing forces with Re­gen­eron on cell ther­a­pies

These days, when Jeffrey Bluestone gets together with his contemporaries in science, the conversation often turns to retirement plans.

But a little more than three years ago, Bluestone reached a momentous turning point in his career, exiting a prestigious post at UCSF, where he had spent decades in the scientific pursuit of new therapies. And it had nothing to do with retirement anytime in the near future.

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Mihael Polymeropoulos, Vanda Pharmaceuticals CEO

Van­da wins court case against FDA over dis­clo­sure of CRL de­tails for sleep drug

DC District Court Judge Christopher Cooper today granted Vanda Pharma’s request to require the FDA to disclose more info on the complete response letter for its sleep disorder drug Hetlioz.

The melatonin receptor agonist is approved by the FDA to treat non-24-hour sleep-wake disorder, a circadian rhythm disorder. But in 2018 Vanda filed a supplemental application to market Hetlioz as a treatment for jet lag, which the FDA rejected in August 2019, with few details on what Vanda needed to correct course, according to the company.

Sally Susman, Pfizer EVP and chief corporate affairs officer

Q&A: Pfiz­er cor­po­rate com­mu­ni­ca­tions chief Sal­ly Sus­man dis­cuss­es book craft­ed in pan­dem­ic and per­son­al lessons

From the political arena to the finance and beauty industries to pharmaceuticals, Pfizer’s Sally Susman has broken barriers, stereotypes and conventions. And now the chief communicator is “Breaking Through,” the title of her first book about effective and innovative communications launching today. The full official title is “Breaking Through: Communicating to Open Minds, Move Hearts, and Change the World.”

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Kevin Lee, Bicycle Therapeutics CEO

No­var­tis rides with Bi­cy­cle for new pact on tar­get­ed ra­dio­ther­a­pies

Novartis has inked a three-year deal with Bicycle Therapeutics to develop new targeted radiotherapies for cancer.

Novartis will pay Bicycle $50 million upfront, with downstream milestones adding up to a potential $1.7 billion. In exchange, Bicycle will use its virus-based platform to discover new bicyclic peptides, which it calls bicycles, that would be used for radiotherapies. Those bicycles would act as a homing beacon for radioactive isotopes, delivering them to cancer cells to kill the cells while limiting radiation to healthy tissue.

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Covant acting CEO Matt Maisak (L) and CSO Iván Cornella

With Boehringer In­gel­heim’s help, Roivant churns out an­oth­er Vant to go up against En­deav­or, Im­pact founders

Roivant Sciences has added another branch to its family tree, unveiling Covant Therapeutics with a $10 million upfront commitment from Boehringer Ingelheim to turn up the heat in cancer.

The Boston-based drug discovery startup will jointly create a new small molecule immunotherapy with the private German pharma giant. The deal, made public Tuesday morning, includes up to $471 million in future payments and tiered royalties, should the product make it to market.

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Gun­ning for 2023 ap­proval, GSK de­tails PhI­II da­ta for Jem­per­li in front­line en­dome­tri­al can­cer

GSK has a new slate of data to offer on its PD-1 inhibitor, Jemperli — data that the pharma giant hopes will cement one of the four drug approvals it’s expecting this year.

While Jemperli (dostarlimab) is already approved for a subset of patients with second-line endometrial cancer, GSK set out in the Phase III RUBY trial to test it as an earlier line of treatment while also enrolling a broader group of patients. In an interim analysis, Jemperli was shown to extend progression-free survival for both the subset and the overall trial population when added to chemotherapy.

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Es­pe­ri­on sues Dai­ichi Sankyo, de­mand­ing pay­ment of $300M mile­stone for car­dio drug

Esperion is suing its business partner Daiichi Sankyo, saying the Japanese drugmaker is improperly refusing to pay a $300 million milestone that the biotech company will be owed after reporting positive data from a large trial of its cardiovascular drug Nexletol.

The 2019 deal between the companies had Daiichi Sankyo pay $150 million upfront plus another $150 million after the first sales of the drug. But another major payout was tied to an outcomes study reported this month, known as CLEAR. Esperion, in its suit against Daiichi, argues that the drug’s more than 20% reduction of heart attack risk is enough to trigger a $300 million payout from Daiichi once it’s added to the drug’s label.

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