Eli Lil­ly, Glax­o­SmithK­line-Vir re­lease pos­i­tive but dif­fi­cult-to-in­ter­pret com­bo an­ti­body da­ta

As vari­ants threat­ened Eli Lil­ly’s so­lo Covid-19 an­ti­body bam­lanivimab, the com­pa­ny teamed with ri­vals on a po­ten­tial com­bo ap­proach. Now they’ve de­clared in­ter­im suc­cess, though it’s not clear whether the re­sults sup­port the com­bo or just show how good their ri­val’s is alone.

The In­di­anapo­lis phar­ma on Mon­day an­nounced that a com­bi­na­tion of bam­lanivimab and the Glax­o­SmithK­line-Vir an­ti­body VIR-7831 suc­cess­ful­ly re­duced vi­ral loads in a Phase II study. Low-risk pa­tients who re­ceived the drug af­ter di­ag­no­sis saw a 70% greater re­duc­tion in virus af­ter 7 days than pa­tients on place­bo. There were al­so sta­tis­ti­cal­ly sig­nif­i­cant vi­ral re­duc­tions af­ter days 3 and 5.

The da­ta show a clear ben­e­fit over bam­lanivimab alone, which HHS has al­ready tak­en out of cir­cu­la­tion be­cause they be­lieve it’s in­suf­fi­cient­ly ef­fec­tive against vari­ants. In bam­lanivimab’s piv­otal tri­al, no dose of the so­lo an­ti­body showed a sta­tis­ti­cal­ly sig­nif­i­cant dif­fer­ence in vi­ral load from place­bo at any time point. The Vir-Lil­ly com­bo al­so showed a larg­er re­duc­tion in vi­ral load at day 7 than Lil­ly’s now-au­tho­rized com­bo of an­ti­bod­ies showed at day 11.

Still, com­par­isons are dif­fi­cult. For one, the da­ta come from just 202 pa­tients in a tri­al that is slat­ed to en­roll 1,000 peo­ple. The com­pa­nies al­so used dif­fer­ent end­points than Lil­ly did in its ear­li­er stud­ies, look­ing at vi­ral loads af­ter a week as op­posed to 11 days. (Af­ter Eli Lil­ly and Re­gen­eron re­leased the first re­sults for their an­ti­bod­ies last fall, out­side ex­perts and the com­pa­nies them­selves point­ed out that be­cause most pa­tients clear the virus af­ter 11 days on their own, it was dif­fi­cult to show a dif­fer­ence with the drug.)

More­over, no one be­sides GSK and Vir has any idea how well VIR-7831 re­duces vi­ral loads on its own. The part­ners re­leased Phase III da­ta ear­li­er this month, an­nounc­ing the drug re­duces hos­pi­tal­iza­tions by 85% — a fig­ure as good as or bet­ter than any of the oth­er Covid-19 an­ti­body ef­forts.

Vir, though, did not re­lease any oth­er de­tails, in­clud­ing on vi­ral loads. With­out that, it’s dif­fi­cult to de­ter­mine whether Lil­ly’s pos­i­tive da­ta are a re­sult of the ad­di­tive or syn­er­gis­tic ef­fects of com­bin­ing bam­lanivimab and VIR-7831, or whether VIR-7831 is do­ing all the virus-neu­tral­iz­ing work and bam­lanivimab is just along the ride.

Lil­ly bet on bam­lanivimab ear­ly in the pan­dem­ic, team­ing with the then-lit­tle known biotech Ab­Cellera to de­vel­op what would ul­ti­mate­ly be­come the first an­ti­body treat­ment au­tho­rized for Covid-19. They won $1.8 bil­lion in gov­ern­ment con­tracts to dis­trib­ute the drug in the US.

Ex­perts, though, con­tin­u­al­ly raised ques­tions about the ef­fec­tive­ness of the dose the FDA au­tho­rized — it missed the pri­ma­ry end­point — and as an­ti­body-re­sis­tant vari­ants spread through­out the US, HHS de­cid­ed to stop ad­min­is­ter­ing bam­lanivimab in a hand­ful of states.

Last week, they stopped ad­min­is­ter­ing it na­tion­wide. It will on­ly now be used in com­bi­na­tion with Lil­ly’s oth­er an­ti­body, in a cock­tail that proved more ef­fec­tive in piv­otal tri­als but which lab da­ta sug­gest may al­so be sus­cep­ti­ble to vari­ants.

Vir’s an­ti­body, by con­trast, ap­peared ef­fec­tive against vari­ants in lab stud­ies. The com­pa­ny filed on Fri­day for an EUA based off the da­ta sug­gest­ing the drug can dra­mat­i­cal­ly re­duce hos­pi­tal­iza­tion. Al­though they have lagged be­hind Lil­ly and Re­gen­eron through much of the last year, the an­ti­body’s ap­par­ent abil­i­ty to neu­tral­ize vari­ants could give the com­pa­ny an up­per hand in the pan­dem­ic’s lat­ter stages.

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.

Covid-19 roundup: No­vavax shakes up lead­er­ship with two pro­mo­tions and de­par­ture of CFO; Mod­er­na, No­vavax shots added to mix-and-match study in the UK

Novavax has had a busy month, filled with supply chain issues and manufacturing deals that have affected the rollout of its Covid-19 vaccine. Tuesday, the company announced updates to its leadership team.

CFO Greg Covino will step down from that role after just five months for personal reasons, the release said, but take on a new role as executive advisor. John Trizzino, current chief commercial officer and chief business officer, will take the CFO role over in the interim.

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.’

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 106,500+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Amy­lyx to move for­ward with ALS pro­gram in Eu­rope, but FDA wants an­oth­er look; Hu­ma­cyte adds $50M in debt fi­nanc­ing

Amylyx is one of several companies looking to break through in the tough ALS field, and Wednesday they announced they’re moving forward with regulatory plans.

The Cambridge, MA-based biotech said they’re submitting a marketing application to the EMA for their AMX0035 program by the end of 2021. Wednesday’s news comes a few weeks after they revealed similar plans to move forward with Canadian health regulators by June 30.

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.

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.