Glax­o­SmithK­line re­thinks strat­e­gy for Covid-19 an­ti­body — not the Vir ones — af­ter tri­al flop. Is there hope in high-risk pa­tients?

In the search for a bet­ter Covid-19 ther­a­peu­tic, Glax­o­SmithK­line and Vir have part­nered up on two an­ti­bod­ies they hope have a chance. GSK is al­so test­ing its own in-house an­ti­body, and ear­ly re­sults may have shut the door on its wide­spread use.

A com­bi­na­tion of GSK’s mon­o­clon­al an­ti­body otil­imab plus stan­dard of care couldn’t best stan­dard of care alone in pre­vent­ing death and res­pi­ra­to­ry fail­ure in hos­pi­tal­ized Covid-19 pa­tients af­ter 28 days, ac­cord­ing to da­ta from the Phase IIa OS­CAR study un­veiled Thurs­day.

Adding otil­imab re­sult­ed in just a 5.3% dif­fer­ence in clin­i­cal out­comes to pa­tients treat­ed with stan­dard of care, not enough to hit sta­tis­ti­cal sig­nif­i­cance. It’s un­clear, how­ev­er, how bad­ly GSK missed the mark in the 806-pa­tient study be­cause the drug­mak­er didn’t re­lease a p-val­ue.

But it’s not nec­es­sar­i­ly game over for otil­imab. In a pre­spec­i­fied analy­sis, 65.1% of otil­imab pa­tients over the age of 70 were alive and hadn’t had a res­pi­ra­to­ry fail­ure at the 28-day mark com­pared with 45.9% of pa­tients in the stan­dard of care arm. That came out to a p-val­ue of 0.0009, well with­in the range of sta­tis­ti­cal sig­nif­i­cance. Mean­while, at the 60-day mark, 26% of pa­tients 70 and up in the otil­imab arm had died com­pared to 40.4% on stan­dard of care alone. That dif­fer­ence just squeaked un­der the sig­nif­i­cance mark at p=0.04.

With some promise in that high-risk co­hort, GSK will ex­pand its 70-and-up co­hort in the OS­CAR study to 350 pa­tients to de­ter­mine whether it will con­tin­ue otil­imab in hos­pi­tal­ized pa­tients in a Phase III test.

Chris Cor­si­co

“Giv­en the pro­found im­pact this pan­dem­ic is hav­ing on the el­der­ly and the en­cour­ag­ing da­ta we are shar­ing to­day, we are hope­ful this find­ing will be repli­cat­ed in the ad­di­tion­al co­hort,” said Chris Cor­si­co, GSK’s se­nior VP of de­vel­op­ment, in a re­lease.

GSK is hop­ing its very mixed re­sults for otil­imab, a gran­u­lo­cyte-macrophage colony-stim­u­lat­ing fac­tor an­ti­body, aren’t repli­cat­ed in the more ad­vanced an­ti­body it’s walk­ing through Phase III tri­als with part­ner Vir Biotech­nol­o­gy.

Back in De­cem­ber, the NIH an­nounced it would test GSK and Vir’s can­di­date, dubbed VIR-7831, as well as an an­ti­body com­bo from Brii Bio­sciences in an ini­tial pop­u­la­tion of 450 mod­er­ate­ly ill Covid-19 pa­tients over the course of five days. Af­ter five days, those pa­tients’ con­di­tions will be as­sessed on two sev­en-point or­di­nal scales; then, based on both can­di­dates’ safe­ty and ef­fi­ca­cy, an ad­di­tion­al 1,050 pa­tients would be added to a sec­ond phase of the study, some of whom may have se­vere ill­ness. The study will as­sess both drugs’ abil­i­ty to in­duce sus­tained re­cov­ery, judged by a hos­pi­tal dis­charge and pa­tients liv­ing at home for 14 days be­fore a 90-day fol­lowup.

Ear­ly re­sults from that study — the NIH’s AC­TIV-3 “mas­ter pro­to­col” — still have yet to be re­port­ed.

The NIH took on GSK and Vir’s an­ti­body soon af­ter it de­cid­ed to scrap LY-CoV555’s shot in AC­TIV-3 study af­ter find­ing lit­tle clin­i­cal ef­fi­ca­cy. At the time, Lil­ly for­ward­ed the the­o­ry that pa­tients in the NIH tri­al may have shown lit­tle ef­fect on LY-CoV555 be­cause they had al­ready been in­fect­ed for a longer du­ra­tion and had re­ceived stan­dard of care as well as Gilead’s remde­sivir pri­or to treat­ment.

The GSK-Vir pair al­so sports a sec­ond part­nered an­ti­body — VIR-7832 — that they an­nounced in Jan­u­ary would en­ter a Phase Ia/IIB study for hos­pi­tal­ized pa­tients and those in the ear­ly stage of the dis­ease. The part­ners think they could have a win­ner there, say­ing their newest an­ti­body has shown an “en­hanced abil­i­ty to clear in­fect­ed cells and po­ten­tial to en­hance virus-spe­cif­ic T cell func­tion, which could help treat and/or pre­vent COVID-19 in­fec­tion.”

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

BY­OD Best Prac­tices: How Mo­bile De­vice Strat­e­gy Leads to More Pa­tient-Cen­tric Clin­i­cal Tri­als

Some of the most time- and cost-consuming components of clinical research center on gathering, analyzing, and reporting data. To improve efficiency, many clinical trial sponsors have shifted to electronic clinical outcome assessments (eCOA), including electronic patient-reported outcome (ePRO) tools.

In most cases, patients enter data using apps installed on provisioned devices. At a time when 81% of Americans own a smartphone, why not use the device they rely on every day?

Voting in the 2020 election (AP Images)

The right to vote is fun­da­men­tal — a let­ter from biotech­nol­o­gy in­dus­try lead­ers

Biotech Voices is a collection of exclusive opinion editorials from some of the leading voices in biopharma on the biggest industry questions today. Think you have a voice that should be heard? Reach out to senior editors Kyle Blankenship and Amber Tong.

We oppose all attempts to introduce laws that reduce the rights of US citizens to vote or that restrict them from exercising that right. The right to vote is fundamental to democracy. States that have enacted, or are proposing to enact, legislation to restrict voting are undermining our democracy and posing a threat to our nation. As leaders of the life sciences industry, we stand for what we believe is right for our country, our enterprises, our employees and those who benefit from our work. We join the first groups of business leaders who have challenged these laws and will continue to make our collective voices heard on this matter.

UP­DAT­ED: J&J paus­es vac­cine roll­out as feds probe rare cas­es of blood clots

The FDA and CDC have jointly decided to stop administering J&J’s Covid-19 vaccine after reviewing data involving six reported US cases of a rare and severe type of blood clot in individuals after receiving the vaccine.

CDC will convene a meeting of its Advisory Committee on Immunization Practices on Wednesday to further review these cases and assess their potential significance. “FDA will review that analysis as it also investigates these cases. Until that process is complete, we are recommending a pause in the use of this vaccine out of an abundance of caution,” Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research and Anne Schuchat, Principal Deputy Director of the CDC, said in a joint statement Tuesday morning.

Pascal Soriot (AstraZeneca via YouTube)

Af­ter be­ing goad­ed to sell the com­pa­ny, Alex­ion's CEO set some am­bi­tious new goals for in­vestors. Then Pas­cal So­ri­ot came call­ing

Back in the spring of 2020, Alexion $ALXN CEO Ludwig Hantson was under considerable pressure to perform and had been for months. Elliott Advisers had been applying some high public heat on the biotech’s numbers. And in reaching out to some major stockholders, one thread of advice came through loud and clear: Sell the company or do something dramatic to change the narrative.

In the words of the rather dry SEC filing that offers a detailed backgrounder on the buyout deal, Alexion stated: ‘During the summer and fall of 2020, Alexion also continued to engage with its stockholders, and in these interactions, several stockholders encouraged the company to explore strategic alternatives.’

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Near­ly a year af­ter Au­den­tes' gene ther­a­py deaths, the tri­al con­tin­ues. What hap­pened re­mains a mys­tery

Natalie Holles was five months into her tenure as Audentes CEO and working to smooth out a $3 billion merger when the world crashed in.

Holles and her team received word on the morning of May 5 that, hours before, a patient died in a trial for their lead gene therapy. They went into triage mode, alerting the FDA, calling trial investigators to begin to understand what happened, and, the next day, writing a letter to alert the patient community so they would be the first to know. “We wanted to be as forthright and transparent as possible,” Holles told me late last month.

The brief letter noted two other patients also suffered severe reactions after receiving a high dose of the therapy and were undergoing treatment. One died a month and a half later, at which point news of the deaths became public, jolting an emergent gene therapy field and raising questions about the safety of the high doses Audentes and others were now using. The third patient died in August.

“It was deeply saddening,” Holles said. “But I was — we were — resolute and determined to understand what happened and learn from it and get back on track.”

Eleven months have now passed since the first death and the therapy, a potential cure for a rare and fatal muscle-wasting disease called X-linked myotubular myopathy, is back on track, the FDA having cleared the company to resume dosing at a lower level. Audentes itself is no more; last month, Japanese pharma giant Astellas announced it had completed working out the kinks of the $3 billion merger and had restructured and rebranded the subsidiary as Astellas Gene Therapies. Holles, having successfully steered both efforts, departed.

Still, questions about precisely what led to the deaths of the 3 boys still linger. Trial investigators released key details about the case last August and December, pointing to a biological landmine that Audentes could not have seen coming — a moment of profound medical misfortune. In an emerging field that’s promised cures for devastating diseases but also seen its share of safety setbacks, the cases provided a cautionary tale.

Audentes “contributed in a positive way by giving a painful but important example for others to look at and learn from,” Terry Flotte, dean of the UMass School of Medicine and editor of the journal Human Gene Therapy, told me. “I can’t see anything they did wrong.”

Yet some researchers say they’re still waiting on Astellas to release more data. The company has yet to publish a full paper detailing what happened, nor have they indicated that they will. In the meantime, it remains unclear what triggered the events and how to prevent them in the future.

“Since Audentes was the first one and we don’t have additional information, we’re kind of in a holding pattern, flying around, waiting to figure out how to land our vehicles,” said Jude Samulski, professor of pharmacology at UNC’s Gene Therapy Center and CSO of the gene therapy biotech AskBio, now a subsidiary of Bayer.

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Launched by MIT grads, a small start­up gets $20M to back a ro­bot­ics rev­o­lu­tion in cell ther­a­py man­u­fac­tur­ing

As co-director of an experimental cellular therapy process development and manufacturing group at UCSF specializing in T cell therapies for autoimmune conditions, Jonathan Esensten has learned a lot about the challenges involved when his group hand-fashions a cell therapy. Esensten — who was a postdoc in Wendell Lim’s lab and counts the legendary Jeffrey Bluestone as a mentor — gives them all high marks at being great at what they do, but time and again there are variations in the treatments they construct.

Anand Shah (FDA)

For­mer head of FDA’s med­ical and sci­en­tif­ic af­fairs on Covid: ‘FDA has nev­er been test­ed like this’

Anand Shah has served the American public in a unique way, crisscrossing over the last two administrations between serving as an attending radiation oncologist focused on prostate cancer at NIH, serving as CMO at the Center for Medicare and Medicaid Innovation, and most recently, leading the FDA’s operations on medical and scientific affairs from within the commissioner’s office.

Shah, who stepped down from the FDA in January, caught up with Endpoints News in a phone interview on Tuesday afternoon, offering his thoughts on the agency’s latest decision to pause the J&J vaccinations in the US, and reflecting on his time at an agency during this once-in-a-lifetime pandemic.

Patrizia Cavazzoni, new CDER director

Pa­trizia Cavaz­zoni named per­ma­nent di­rec­tor of CDER, adding to ques­tions around where Wood­cock will end up

Patrizia Cavazzoni on Monday became the permanent director of the FDA’s Center for Drug Evaluation and Research, which puts to rest the idea that Janet Woodcock, Cavazzoni’s predecessor, might return to lead CDER if she isn’t made permanent commissioner.

Woodcock, who’s currently serving as acting commissioner and principal medical advisor to the commissioner, a position she was detailed to last year, may not make the move to permanent commissioner because of lingering questions from Senate Democrats. She previously served as director of CDER since 1994. Cavazzoni took over as acting director of CDER when Woodcock moved over to Operation Warp Speed to run the therapeutics side of the Trump-era program.

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Barbara Weber, Tango Therapeutics CEO (Tango)

It takes two to Tan­go: The biotech us­ing CRISPR to dis­cov­er new can­cer gene tar­gets rides a $353M SPAC deal to Nas­daq

Editor’s note: Interested in following biopharma’s fast-paced IPO market? You can bookmark our IPO Tracker here.

The latest biotech-SPAC deal has arrived, and it’s dancing its way to Nasdaq to the tune of several hundred million dollars.

Tango Therapeutics and its CRISPR-focused search for new cancer genes is reverse merging with Boxer Capital’s blank-check company, the biotech announced Wednesday morning. With a spotlight on three lead programs, Tango expects total proceeds to equal about $353 million in the deal, which includes the roughly $167 million held in the SPAC and an additional $186 million in PIPE financing.