UP­DAT­ED: As­traZeneca says mon­o­clon­al an­ti­body com­bo is 77% ef­fec­tive at pre­vent­ing Covid-19

Af­ter hit­ting just about every pot­hole with its Covid-19 vac­cine roll­out, As­traZeneca has some good news to share for an­oth­er pan­dem­ic-re­lat­ed pro­gram: Its mon­o­clon­al an­ti­body com­bo, AZD7442, proved ef­fec­tive at pre­vent­ing symp­to­matic Covid-19 in a Phase III study.

AZD7442 re­duced the risk of symp­to­matic Covid-19 by 77%, based on a pre­lim­i­nary group of cas­es in a large, glob­al Phase III tri­al, ac­cord­ing to the British phar­ma. The study, dubbed PROVENT, en­rolled near­ly 5,200 vol­un­teers across the US, UK, Spain, France and Bel­gium, 75% of whom had co­mor­bidi­ties or con­di­tions that would cause a re­duced im­mune re­sponse to vac­ci­na­tion.

“We in­ten­tion­al­ly re­cruit­ed peo­ple at high risk or an in­creased risk for an in­ad­e­quate re­sponse to vac­ci­na­tion, or hav­ing a se­vere SARS-CoV-2 in­fec­tion,” Mark Ess­er, VP of mi­cro­bial sci­ences and bio­phar­ma­ceu­ti­cals R&D, told re­porters in a press con­fer­ence on Fri­day morn­ing.

Of 25 re­port­ed Covid-19 cas­es at the pre­lim­i­nary read­out, there were no se­vere cas­es or deaths in the treat­ment arm, and three se­vere cas­es and two deaths in the place­bo arm.

That’s all the ef­fi­ca­cy da­ta As­traZeneca is shar­ing for now, though the com­pa­ny says it’s run­ning the re­sults to reg­u­la­tors in pur­suit of an emer­gency use au­tho­riza­tion or con­di­tion­al ap­proval for the pre­ven­tion of Covid-19.

“We don’t nor­mal­ly talk about sub­mis­sion time­lines. The team is be­ing pushed very hard to try and get a sub­mis­sion in with­in, you know, I would say a few weeks,” EVP of bio­phar­ma­ceu­ti­cals R&D Mene Pan­ga­los said dur­ing the call. “I think it’s not un­re­al­is­tic to hope that we might get an ap­proval be­fore the end of the year,” he added.

While the read­out looks at da­ta col­lect­ed be­fore the Delta vari­ant gained promi­nence across the globe, As­traZeneca says it has pre­lim­i­nary in vit­ro da­ta sug­gest­ing the AZD7442 neu­tral­izes emerg­ing vari­ants, in­clud­ing Delta. Ad­verse events were bal­anced be­tween the place­bo and treat­ment groups, ac­cord­ing to Pan­ga­los.

“There’s noth­ing that’s stand­ing out in terms of ad­verse events,” he said.

The phar­ma is eval­u­at­ing AZD7442 in a va­ri­ety of set­tings. The can­di­date — dis­cov­ered by the Van­der­bilt Uni­ver­si­ty Med­ical Cen­ter and li­censed to As­traZeneca last June — is a com­bi­na­tion of the an­ti­bod­ies tix­agevimab and cil­gav­imab, de­rived from B cells do­nat­ed by re­cov­ered Covid-19 pa­tients.

In ad­di­tion to the 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.

Pro­phy­lac­tic treat­ments like AZD7442 could prove use­ful for those with weak­er im­mune sys­tems, or those who don’t re­spond well to a vac­cine. That in­cludes pa­tients who are on chemother­a­py, have blood can­cers, or are tak­ing im­muno­sup­pres­sants, among oth­ers. And as the rise of con­cern­ing vari­ants ren­ders pre­vi­ous­ly au­tho­rized treat­ments in­ef­fec­tive, the US is look­ing for any­thing it can get to stave off se­vere cas­es.

Mene Pan­ga­los

The fed­er­al gov­ern­ment struck a deal with As­traZeneca back in March for an ex­tra half-mil­lion dos­es of AZD7442, build­ing on its ex­ist­ing 100,000-dose or­der from Oc­to­ber. The com­pa­ny al­so has a sep­a­rate agree­ment with the De­part­ment of De­fense for 100,000 dos­es, bring­ing its to­tal com­mit­ment to the US up to 700,000 dos­es in 2021.

While no vol­un­teers in PROVENT had been vac­ci­nat­ed be­fore join­ing the study, As­traZeneca says it sees AZD7442 as a sup­ple­ment to the cur­rent­ly ap­proved vac­cines. While it can be tak­en alone, the re­al­i­ty is a ma­jor­i­ty of peo­ple will like­ly use it in ad­di­tion to a vac­cine, Pan­ga­los said. Over the course of the study, more than 400 peo­ple in the treat­ment arm de­cid­ed to opt out and get vac­ci­nat­ed, and re­searchers have seen “no is­sues there,” ac­cord­ing to Ess­er.

“We’ve done pre­clin­i­cal stud­ies in non-hu­man pri­mates or mon­keys to show that the an­ti­body doesn’t in­ter­fere with vac­ci­na­tion, and we hope to pub­lish that short­ly,” he added.

The com­pa­ny de­clined to com­ment on how much the treat­ment might cost, if even­tu­al­ly au­tho­rized by reg­u­la­tors.

The news comes a cou­ple months af­ter the US paused the use of Eli Lil­ly’s an­ti­body com­bo, urg­ing care­givers to opt for Re­gen­eron’s cock­tail as an al­ter­na­tive be­cause it’s more ef­fec­tive against the vari­ants.

As­traZeneca’s cel­e­brat­ing the good news af­ter a rocky vac­cine roll­out, in­clud­ing a le­gal bat­tle over ship­ment de­lays in the EU and re­ports of rare blood clots in those who re­ceived the vac­cine.

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

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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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.

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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Biospec­i­men M&A: Dis­cov­ery ac­quires Al­bert Li's he­pa­to­cyte project; PhI­II tri­al on Bay­er's Nube­qa reached pri­ma­ry end­point

Discovery Life Sciences has acquired what claims to be the Maryland-based host of the world’s largest hepatocyte inventory, known as IVAL, to help researchers select more effective and safer drug candidates in the future.

The combined companies will now serve a wider range of drug research and development scientists, according to Albert Li, who founded IVAL in 2004 and is set to join the Discovery leadership team as the CSO of pharmacology and toxicology.

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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Ugur Sahin, BioNTech CEO (Bernd von Jutrczenka/dpa via AP Images)

Covid-19 roundup: Ugur Sahin says new shots like­ly need­ed for Omi­cron; UK ful­ly ap­proves Vir/Glax­o­SmithK­line an­ti­body

Despite Ugur Sahin’s calls for calm over the Omicron variant — making a much more measured appeal than Moderna CEO Stéphane Bancel — the BioNTech chief is already predicting the potential need for new Covid-19 vaccines.

In comments made at a conference hosted Friday morning by Reuters, Sahin said that even though vaccinated individuals would likely still be protected from severe disease, Omicron could see greater numbers of breakthrough infections than other variants. The mutations mean Covid shots will probably become necessary every year, similar to the flu.