With piv­otal da­ta on its Covid-19 an­ti­body in hand, As­traZeneca pre­pares for a mad dash to the FDA

A month af­ter re­veal­ing that its mon­o­clon­al an­ti­body com­bi­na­tion was 77% ef­fec­tive at pre­vent­ing symp­to­matic Covid-19 com­pared to place­bo, As­traZeneca says it’s head­ed to the FDA.

“We’ve cer­tain­ly shared the da­ta with reg­u­la­tors, and we an­tic­i­pate sub­mit­ting the emer­gency use au­tho­riza­tion very short­ly,” Mark Ess­er, VP and head of mi­cro­bial sci­ences and bio­phar­ma­ceu­ti­cals R&D, said dur­ing a press con­fer­ence on Wednes­day af­ter­noon.

Just eight of 3,460 vol­un­teers giv­en AZD7442 in the Phase III PROVENT tri­al came down with symp­to­matic Covid-19 over a six-month pe­ri­od, Ess­er said, com­pared to 17 of 1,737 peo­ple in the place­bo group.

The study en­rolled par­tic­i­pants across the US, UK, Spain, France and Bel­gium, many of whom had co­mor­bidi­ties or oth­er con­di­tions that would cause a re­duced im­mune re­sponse to vac­ci­na­tion. That in­clud­ed peo­ple on im­muno­sup­pres­sive drugs, or with dis­eases like di­a­betes, smok­ing-re­lat­ed lung dis­ease, kid­ney dis­ease, and chron­ic liv­er dis­ease, among oth­ers.

Over­all, the ther­a­py post­ed a 77% ef­fi­ca­cy rate — a sig­nif­i­cant­ly high­er rate than the 63% ef­fi­ca­cy re­port­ed to the WHO for the com­pa­ny’s own Covid-19 vac­cine. At an in­ter­im read­out in March, As­traZeneca had re­port­ed that its vac­cine was 70% ef­fec­tive at pre­vent­ing symp­to­matic Covid-19, which was slight­ly high­er than the 62% fig­ure post­ed in the UK.

There were no se­vere cas­es or deaths in the AZD7442 treat­ment arm, and three se­vere cas­es and two deaths in the place­bo arm, the phar­ma said. Though it’s un­clear how the FDA may view the tri­al’s rel­a­tive­ly small sam­ple size.

De­spite the pos­i­tive ef­fi­ca­cy re­sults, Ess­er stressed that AZD7442 is in­tend­ed for use on top of vac­ci­na­tion, not in lieu of it.

Mark Ess­er

“First and fore­most, we want peo­ple to get vac­ci­nat­ed. We know the vac­cines work in most peo­ple,” he said. “Now, if there is some­one who’s had an al­ler­gic re­ac­tion to one of the vac­cines, or for some rea­son can­not get vac­ci­nat­ed, I think 7442 could be a so­lu­tion for that.”

AZD7442 was dis­cov­ered by the Van­der­bilt Uni­ver­si­ty Med­ical Cen­ter, and li­censed to As­traZeneca last June. It’s a com­bi­na­tion of the an­ti­bod­ies tix­agevimab and cil­gav­imab, de­rived from B cells do­nat­ed by a hus­band and wife team who had re­cov­ered from Covid-19. The ben­e­fit of a mon­o­clon­al an­ti­body is that it pro­vides “al­most im­me­di­ate” pro­tec­tion, where­as cur­rent vac­cines ap­proved in the US take a cou­ple weeks to kick in.

The down­side is that the du­ra­tion of pro­tec­tion is much short­er. As­traZeneca says it has tech­nol­o­gy that can ex­tend the an­ti­body’s half life from an av­er­age of around 20 days to 90 days.

“What this means is that a sin­gle in­tra­mus­cu­lar shot could eas­i­ly af­ford six months, and we’re hope­ful up to 12 months of pro­tec­tion,” Ess­er said on the call.

In ad­di­tion to PROVENT, AZD7442 is al­so in the on­go­ing TACK­LE COVID-19 pro­gram, which looks at the an­ti­bod­ies’ abil­i­ty to treat and pre­vent Covid across more than 9,000 par­tic­i­pants in the out­pa­tient set­ting. And while vol­un­teers got the can­di­date in­ject­ed in­to the mus­cle in PROVENT, it’s al­so be­ing as­sessed as an IV drug.

Back in June, AZD7442 missed the mark in a study as­sess­ing its abil­i­ty to pre­vent symp­toms in adults who had a con­firmed ex­po­sure to Covid-19. As­traZeneca says the an­ti­body com­bo per­formed bet­ter in a pre-planned analy­sis of PCR-neg­a­tive vol­un­teers.

Ess­er says he’s “quite con­fi­dent” AZD7442 will work against the Delta vari­ant, as well as oth­er emerg­ing vari­ants, adding that there were few Delta cas­es re­port­ed in the treat­ment arm, and many in the place­bo arm. He said the com­pa­ny is se­quenc­ing the virus­es, and will have more da­ta to share soon.

Hugh Mont­gomery, a pro­fes­sor of med­i­cine and di­rec­tor of the Cen­tre for Hu­man Health and Per­for­mance at Uni­ver­si­ty Col­lege in Lon­don, point­ed to the ben­e­fit of hav­ing two long-act­ing an­ti­bod­ies.

“If one was look­ing at the risk of vi­ral es­cape down the line, the chances of get­ting two mu­ta­tions to pre­vent these an­ti­bod­ies bind­ing would be very, very un­like­ly,” Mont­gomery said.

The news comes a month af­ter fed­er­al of­fi­cials reau­tho­rized Eli Lil­ly’s an­ti­body com­bo, which had been tak­en off the mar­ket due to a “sus­tained in­crease” of coro­n­avirus vari­ants in the US. That com­bo — bam­lanivimab and ete­se­vimab — is now au­tho­rized in states where the fre­quen­cy of re­sis­tant vari­ants like the Delta-plus or Gam­ma is 5% or low­er.

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

All about Omi­cron; We need more Covid an­tivi­rals; GSK snags Pfiz­er’s vac­cine ex­ec; Janet Wood­cock’s fu­ture at FDA; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

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Merck's new antiviral molnupiravir (Quality Stock Arts / Shutterstock)

As Omi­cron spread looms, oral an­tivi­rals ap­pear to be one of the best de­fens­es — now we just need more

After South African scientists reported a new Covid-19 variant — dubbed Omicron by the WHO — scientists became concerned about how effective vaccines and monoclonal antibodies might be against it, which has more than 30 mutations in the spike protein.

“I think it is super worrisome,” Dartmouth professor and Adagio co-founder and CEO Tillman Gerngross told Endpoints News this weekend. Moderna CEO Stéphane Bancel echoed similar concerns, telling the Financial Times that experts warned him, “This is not going to be good.”

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Pfiz­er, Am­gen and Janssen seek fur­ther clar­i­ty on FDA's new ben­e­fit-risk guid­ance

Three top biopharma companies are seeking more details from the FDA on how the agency conducts its benefit-risk assessments for new drugs and biologics.

While Pfizer, Amgen and Janssen praised the agency for further spelling out its thinking on the subject in a new draft guidance, including a discussion of patient experience data as part of the assessment, the companies said the FDA could’ve included more specifics in the 20-page draft document.

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Re­searchers move clos­er to de­ci­pher­ing blood clots from As­traZeneca, J&J's Covid-19 vac­cines

Researchers may be nearing an answer for the mysterious and life-threatening blood clots that appeared on very rare occasions in people who received the J&J or AstraZeneca Covid-19 vaccine.

The new work builds on an early hypothesis researchers in Norway put forward last spring, when the cases first cropped up. They proposed the events were similar to blood clots that can occur in a small subset of patients who receive heparin, one of the most commonly used blood thinners.

Janet Woodcock (AP Images)

Janet Wood­cock plots her fu­ture at FDA, with se­nior ad­vi­sor role to fall back on if Califf wins con­fir­ma­tion

Acting FDA commissioner Janet Woodcock has been the face of just about every drug approval decision at the agency since the turn of the century. Since the pandemic began, she’s moved between the top of the drugs center to the head of therapeutics at Operation Warp Speed, leading the drive for work on Covid-targeted mAbs and antivirals.

Looking forward — and pending a quick Senate confirmation to cement Rob Califf’s return to the top of FDA early next year — Woodcock’s role at the agency will again be in flux.

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Richard Pazdur (via AACR)

Ac­cel­er­at­ed ap­proval re­forms need mean­ing­ful con­fir­ma­to­ry tri­al im­prove­ments, pro­fes­sors write in Sci­ence

Outside of Covid-19, 2021 has been the year of the accelerated approval.

Beginning last spring, FDA openly challenged six “dangling” accelerated approvals (hadn’t confirmed their clinical benefit yet), three of which were later pulled by the companies.

Then in June, FDA pulled out the accelerated approval pathway, seemingly out of nowhere, to sign off on Biogen’s controversial Alzheimer’s drug Aduhelm. It hadn’t even been mentioned at the drug’s adcomm.

Usama Malik

Ex-Im­munomedics CFO charged with in­sid­er trad­ing, faces up to 20 years in prison af­ter al­leged­ly tip­ping off girl­friend and rel­a­tives of a PhI­II suc­cess

The former CFO of Immunomedics, who helped steer the company to its $21 billion buyout by Gilead last year, has been charged with insider trading, the Department of Justice announced Thursday.

Usama Malik tipped off his then-girlfriend and four others that a Phase III study for Trodelvy would be stopped early four days before Immunomedics publicly announced the result in April 2020, DoJ alleged in its complaint. The individuals then purchased Immunomedics shares, selling them after the news broke and Immunomedics’ stock price doubled.

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Ab­b­Vie tacks on a new warn­ing to Rin­voq la­bel as safe­ty frets crimp JAK class

The safety problems that continue to plague the JAK class as new data highlight some severe side effects are casting a large shadow over AbbVie’s Rinvoq.

As a result of a recent readout highlighting major adverse cardiac events (MACE), malignancy, mortality and thrombosis with Xeljanz a couple of months ago, AbbVie put out a notice late Friday afternoon that it is adding the new class risks to its label for their rival drug.

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