Covid-19 roundup: South African vari­ant trips up Pfiz­er/BioN­Tech, Mod­er­na vac­cines while EU seeks an­ti-vari­ant con­tract claus­es — re­port

As ques­tions con­tin­ue to swirl about the ef­fec­tive­ness of cur­rent vac­cines against new vari­ants of the coro­n­avirus, a pair of let­ters to the ed­i­tor con­firm that those de­vel­oped by Pfiz­er/BioN­Tech and Mod­er­na ap­pear to be able to pro­tect against the UK vari­ant but less ef­fi­ca­cious when faced with the strain orig­i­nat­ing from South Africa.

Now that the first-gen­er­a­tion vac­cines’ ef­fi­ca­cy against the orig­i­nal SARS-CoV-2 anti­gen has large­ly been es­tab­lished, some sci­en­tists have turned their at­ten­tion to the ques­tions of when, where and how they can be best de­ployed.

The South African vari­ant has al­ready raised glob­al alarms af­ter As­traZeneca’s Ox­ford-part­nered vac­cine was side­lined af­ter it failed a small-scale analy­sis specif­i­cal­ly mea­sur­ing its ef­fi­ca­cy against B.1.351.

Writ­ing to the New Eng­land Jour­nal of Med­i­cine, two dif­fer­ent groups re­port­ed sim­i­lar find­ings about the serum neu­tral­iz­ing ac­tiv­i­ty elicit­ed by the Pfiz­er/BioN­Tech and Mod­er­na shots.

From the let­ter on BNT162b2:

Thus, as com­pared with neu­tral­iza­tion of USA-WA1/2020, neu­tral­iza­tion of Δ242-244+D614G virus was sim­i­lar and neu­tral­iza­tion of the B.1.351-spike virus was weak­er by ap­prox­i­mate­ly two thirds. Our da­ta are al­so con­sis­tent with poor­er neu­tral­iza­tion of the virus with the full set of B.1.351-spike mu­ta­tions than virus with ei­ther sub­set of mu­ta­tions and sug­gest­ed that virus with mu­tant residues in the re­cep­tor-bind­ing site (K417N, E484K, and N501Y) is more poor­ly neu­tral­ized than virus with Δ242-244, which is lo­cat­ed in the N-ter­mi­nal do­main of the spike pro­tein.

Mean­while with mR­NA-1273:

Both the full pan­el of mu­ta­tions in S and a sub­set of mu­ta­tions af­fect­ing the re­cep­tor-bind­ing do­main (RBD) re­gion of the B.1.1.7 vari­ant had no sig­nif­i­cant ef­fect on neu­tral­iza­tion by serum ob­tained from par­tic­i­pants who had re­ceived the mR­NA-1273 vac­cine in the phase 1 tri­al (Fig­ure 1A and 1B). In con­trast, we ob­served a de­crease in titers of neu­tral­iz­ing an­ti­bod­ies against the B.1.351 vari­ant and a sub­set of its mu­ta­tions af­fect­ing the RBD.

In a third let­ter, two Cana­di­an re­searchers sug­gest that the two dos­es of the Pfiz­er/BioN­Tech vac­cine should be giv­en at a longer in­ter­val than cur­rent­ly pre­scribed, based on a new analy­sis on the da­ta both com­pa­nies sub­mit­ted to the FDA.

One dose of the vac­cine, they ar­gue, is ac­tu­al­ly high­er than the 52.4% fig­ure that Phase III in­ves­ti­ga­tors had orig­i­nal­ly thought. If you re­move da­ta from the first two weeks af­ter the first dose, “when im­mu­ni­ty would have still been mount­ing,” the ef­fi­ca­cy would ac­tu­al­ly be much high­er.

“Even be­fore the sec­ond dose, BNT162b2 was high­ly ef­fi­ca­cious, with a vac­cine ef­fi­ca­cy of 92.6%, a find­ing sim­i­lar to the first-dose ef­fi­ca­cy of 92.1% re­port­ed for the mR­NA-1273 vac­cine (Mod­er­na),” they wrote. “Giv­en the cur­rent vac­cine short­age, post­pone­ment of the sec­ond dose is a mat­ter of na­tion­al se­cu­ri­ty that, if ig­nored, will cer­tain­ly re­sult in thou­sands of Covid-19–re­lat­ed hos­pi­tal­iza­tions and deaths this win­ter in the Unit­ed States — hos­pi­tal­iza­tions and deaths that would have been pre­vent­ed with a first dose of vac­cine.” — Am­ber Tong

EU seek­ing an­ti-vari­ant con­tract claus­es — re­port

With the emer­gence of new Covid-19 virus vari­ants and un­cer­tain­ty sur­round­ing vac­cines’ pro­tec­tion against them, the EU is re­port­ed­ly look­ing to en­sure ac­cess to po­ten­tial boost­er shots in its deals with vac­cine mak­ers.

The bloc is adding an­ti-vari­ant claus­es to new vac­cine sup­ply con­tracts and seek­ing to amend its old­er deals, Reuters re­port­ed, with lan­guage that ex­plic­it­ly cov­ers the vari­ants. The ne­go­ti­a­tions come amid the pub­li­ca­tion of stud­ies from Pfiz­er and Mod­er­na that sug­gest low­er an­ti­body lev­els against the South African vari­ant and South Africa it­self halt­ing roll­out of the As­traZeneca/Ox­ford vac­cine af­ter it showed high­ly di­min­ished ef­fi­ca­cy fight­ing the vari­ant in a small tri­al.

Three EU sources con­firmed the news to Reuters, with one of­fi­cial say­ing the claus­es would al­low the bloc to fo­cus on buy­ing up­grad­ed shots rather than vac­cines that are not ef­fec­tive against the wide­spread vari­ants. How­ev­er, the source added the de­f­i­n­i­tion of “vari­ant” in the new con­tracts re­mained vague, and it was un­clear what le­gal pow­er the con­tracts would give the EU.

All three con­firmed that one of these claus­es was in­clud­ed in the new EU con­tract with Pfiz­er and BioN­Tech signed ear­li­er this month. The deal is ex­pect­ed to sup­ply 300 mil­lion ad­di­tion­al dos­es of the pair’s mR­NA vac­cine.

In to­tal, the EU has se­cured deals to ac­quire rough­ly 2.6 bil­lion vac­cines from six com­pa­nies, and is still ne­go­ti­at­ing with No­vavax, Val­ne­va and Mod­er­na to pur­chase even more.

On Wednes­day af­ter­noon, Pfiz­er and Mod­er­na pub­lished re­search in the New Eng­land Jour­nal of Med­i­cine say­ing their vac­cines still of­fer enough pro­tec­tion to neu­tral­ize the South African vari­ant, but pro­duce sig­nif­i­cant­ly few­er an­ti­bod­ies in re­sponse. The study was con­duct­ed in a lab­o­ra­to­ry set­ting and it re­mains un­clear whether the same re­sponse would be seen in re­al life. — Max Gel­man

Mex­i­co fac­to­ry pro­duc­ing As­traZeneca shot al­most ful­ly up­grad­ed

Mex­i­co had been prepar­ing to pack­age and dis­trib­ute the As­traZeneca/Ox­ford vac­cine through­out Cen­tral Amer­i­ca, but that process had been held up by nec­es­sary fac­to­ry changes. Now, the coun­try is al­most ready to start.

The fac­to­ry up­grade had been held up by a se­ries of com­plex cer­ti­fi­ca­tion process­es af­ter health reg­u­la­tors could not de­ter­mine whether the plant could safe­ly pro­duce Covid-19 shots, Reuters re­port­ed. On an in­spec­tion vis­it to the fac­to­ry, which pre­vi­ous­ly made flu shots, of­fi­cials not­ed 185 “ob­ser­va­tions” that need­ed to be fixed.

“They al­most had to make an­oth­er fac­to­ry,” Mex­i­can for­eign min­is­ter Marce­lo Ebrard said at a gov­ern­ment news con­fer­ence, per Reuters. “You are talk­ing about health, life … so you do have to be very strict in any med­i­cine, with a vac­cine more, and even more when the vac­cine is so re­cent.”

Mex­i­co had re­ceived at least two ship­ments of As­traZeneca’s ac­tive vac­cine in­gre­di­ent but had not fin­ished pro­duc­ing dos­es of the shot. The fac­to­ry is now ex­pect­ed to start ship­ping the dos­es by ear­ly April, Ebrard said.

With the back­ing of Mex­i­can bil­lion­aire Car­los Slim, As­traZeneca had reached agree­ments with Mex­i­co and Ar­genti­na to dis­trib­ute their shots through­out the Cen­tral and South Amer­i­can re­gions. Mex­i­co al­so is aim­ing to speed up its vac­cine cam­paign, hav­ing im­port­ed 870,000 As­traZeneca shots from In­dia on Sun­day. — Max Gel­man

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.

Lisa Deschamps, AviadoBio CEO

Ex-No­var­tis busi­ness head hops over to a gene ther­a­py start­up — and she's reeled in $80M for a dash to the clin­ic

Neurologist and King’s College London professor Christopher Shaw has been researching neurodegenerative diseases like ALS and collaborating with drugmakers for the last 25 years in the hopes of pushing new therapies forward. But unfortunately, none of those efforts have come anywhere close to fruition.

“So, you know, after 20 years in the game, I said, ‘Let’s try and do it ourselves,’” he told Endpoints News. 

In­cor­po­rat­ing Ex­ter­nal Da­ta in­to Clin­i­cal Tri­als: Com­par­ing Dig­i­tal Twins to Ex­ter­nal Con­trol Arms

Most drug development professionals are familiar with the nerve-racking wait for the read-out of a large trial. If it’s negative, is the investigational therapy ineffective? Or could the failure result from an unforeseen flaw in the design or execution of the protocol, rather than a lack of efficacy? The team could spend weeks analyzing data, but a definitive answer may be elusive due to insufficient power for such analyses in the already completed trial. These problems are only made worse if the trial had lower enrollment, or higher dropout than expected due to an unanticipated event like COVID-19. And if a trial is negative, the next one is likely to be larger and more costly — if it happens at all.

As first Omi­cron case in US crops up, re­searchers won­der: Which an­ti­bod­ies, vac­cines will hold up?

As Covid-19 drug and vaccine developers race to figure out which of their products might be hampered by the new variant, the CDC on Wednesday afternoon announced the first confirmed case of the Omicron variant (B.1.1.529) in the US, found in San Francisco.

The unidentified individual was a traveler who returned from South Africa on Nov. 22, 2021, was fully vaccinated, and had mild symptoms that the CDC described as improving. All close contacts have been contacted and have tested negative, the centers said.

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Mod­er­na los­es lat­est bat­tle in key vac­cine de­liv­ery patent fight as fed­er­al ap­peal falls flat

The US Court of Appeals for the Federal Circuit on Wednesday rejected Moderna’s attempt to overturn key patents related to the delivery vehicle for its Covid-19 vaccine after the biotech sought to preempt a potentially risky infringement lawsuit.

For years, Moderna has been battling a tiny Pennsylvania biotech known as Arbutus over patents for a technology required to deliver its mRNA drugs and vaccines, known as lipid nanoparticles or LNP. Moderna is concerned there’s a substantial risk that Arbutus will assert the ’069 patent in an infringement suit targeting Moderna’s Covid-19 vaccine, particularly as Arbutus has boasted of its patent protection and refused to grant a covenant not to sue Moderna.

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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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