The vac­cine race is shap­ing up to be much more than just a sprint to­ward au­tho­riza­tion.

A day af­ter Mer­ck dropped out en­tire­ly, con­tro­ver­sies are sim­mer­ing around As­traZeneca and Pfiz­er/BioN­Tech, J&J says it will come along soon, while Mod­er­na is re­fu­el­ing for the long haul.

With vac­cine roll­out still in bot­tle­necks even across wealthy na­tions that have es­sen­tial­ly bought up ini­tial sup­plies, the emer­gence of new vari­ants is com­pli­cat­ing long-term plan­ning. For late­com­ers, who must now make crit­i­cal de­ci­sions about their still-ex­per­i­men­tal pro­grams, ques­tions re­main on just what lev­els of ef­fi­ca­cy are good enough — and for whom.

“We con­tin­ue to progress our COVID-19 vac­cine can­di­date and look for­ward to shar­ing de­tails from our Phase 3 study soon,” J&J CEO Alex Gorsky said in an an­nounce­ment of quar­ter­ly re­sults, just be­fore he told CN­BC they ex­pect those re­sults next week.

J&J CFO tells @CN­BC he ex­pects to re­lease vac­cine re­sults next week. "We're op­ti­mistic. We think we're go­ing to have a very ro­bust da­ta set."@CN­BC

— Carl Quin­tanil­la (@car­lquin­tanil­la) Jan­u­ary 26, 2021

EU blasts As­traZeneca for vac­cine pro­duc­tion de­lays, threat­ens ex­port con­trol

As­traZeneca may still be days away from win­ning an an­tic­i­pat­ed OK for its vac­cine in the EU, but the trou­bles and con­tro­ver­sy are al­ready pour­ing in.

The phar­ma gi­ant was swarmed by back­lash on Mon­day af­ter it in­formed the Eu­ro­pean bloc that pro­duc­tion lags mean it would not be able to de­liv­er the promised num­ber of dos­es laid out in a sup­ply con­tract. That fol­lowed re­ports in Ger­man me­dia claim­ing that the vac­cine, de­vel­oped on ade­n­ovirus tech­nolo­gies out of Ox­ford Uni­ver­si­ty, had an ex­treme­ly low ef­fi­ca­cy in those over 65 — which As­traZeneca de­nied.

So far, the AZD1222 jab has on­ly been ap­proved in the UK. But the EMA is re­port­ed­ly set to make a de­ci­sion this week.

In a meet­ing with As­traZeneca, EU of­fi­cials all but ac­cused the com­pa­ny of pri­or­i­tiz­ing oth­er na­tions at the ex­pense of their mem­ber coun­tries, Politi­co re­port­ed. They sub­se­quent­ly called for tighter con­trols on coro­n­avirus vac­cine ex­ports.

Stel­la Kyr­i­akides, the Eu­ro­pean Com­mis­sion­er for Health and Food Safe­ty, aired her dis­sat­is­fac­tion pub­licly:

Dis­cus­sions with @As­traZeneca to­day re­sult­ed in dis­sat­is­fac­tion with the lack of clar­i­ty and in­suf­fi­cient ex­pla­na­tions. EU Mem­ber States are unit­ed: vac­cine de­vel­op­ers have so­ci­etal and con­trac­tu­al re­spon­si­bil­i­ties they need to up­hold.

— Stel­la Kyr­i­akides (@SKyr­i­akidesEU) Jan­u­ary 25, 2021

Be­hind the scenes, one EU diplo­mat de­scribed to Politi­co two rea­sons giv­en by As­traZeneca for the pro­duc­tion short­fall at a Bel­gium plant: ma­te­ri­als sourc­ing and man­u­fac­tur­ing. But with a dearth of ev­i­dence to sup­port those ex­pla­na­tions, they al­so not­ed that the com­pa­ny had al­ready shipped dos­es made in that fa­cil­i­ty to oth­er cus­tomers around the world.

The EU had cut a deal to pre-or­der 300 mil­lion dos­es at an undis­closed price, with an op­tion to add 100 mil­lion.

“Trust has been se­vere­ly shak­en,” a Com­mis­sion of­fi­cial said, adding: “To this day, it has not been ful­ly ex­plained what hap­pened to the mon­ey and what has the com­pa­ny done on its oblig­a­tion to man­u­fac­ture at risk.” — Am­ber Tong

Mod­er­na con­sid­ers third boost­er dose to squash new vari­ants

Mod­er­na is test­ing boost­er op­tions to be sure its Covid-19 vac­cine can stamp out emerg­ing vari­ants — which could mean a third shot for some par­tic­i­pants.

The biotech has been fol­low­ing a range of vari­ants, at least five of which in­volve mul­ti­ple mu­ta­tions, pres­i­dent Stephen Hoge said dur­ing an in­vestor call Mon­day af­ter­noon. The three gain­ing the most at­ten­tion are: B.1.1.7, first de­tect­ed in the UK; B.1.351, iden­ti­fied in South Africa; and P.1, found in Brazil and Japan.

The UK vari­ant has 17 ge­net­ic mu­ta­tions in the vi­ral genome, with eight lo­cat­ed on the spike pro­tein. The South Africa vari­ant has 10 mu­ta­tions to the spike pro­tein. And all three strains have de­vel­oped mul­ti­ple mu­ta­tions at the top of the spike pro­tein, near the re­cep­tor bind­ing do­main and the N-ter­mi­nal do­main (NTD).

“These are a par­tic­u­lar con­cern, be­cause when we de­vel­op an­ti­bod­ies that neu­tral­ize and pro­tect against the coro­n­avirus, we re­al­ly find that the an­ti­bod­ies that bind at the top of the spike pro­tein are par­tic­u­lar­ly ef­fec­tive,” Hoge said.

To see if their vac­cine, mR­NA-1273, of­fers pro­tec­tion against the new strains, Mod­er­na con­duct­ed in vi­vo stud­ies us­ing sera from eight Phase I par­tic­i­pants who re­ceived two 100 µg dos­es, and from pri­mates giv­en ei­ther two 30 µg or 100 µg dos­es.

The re­sults? The vac­cine worked well enough, ap­pear­ing to be “ful­ly ef­fec­tive” against all strains test­ed, ac­cord­ing to Hoge. The not-so-good news is that there was a six-fold re­duc­tion in neu­tral­iz­ing an­ti­body titers against the South Africa vari­ant. While the lev­els are still be­lieved to be high enough to be pro­tec­tive, they may lead to ear­li­er wan­ing of im­mu­ni­ty, ac­cord­ing to Mod­er­na.

Mod­er­na is test­ing boost­ers “out of an abun­dance of cau­tion,” CEO Stéphane Ban­cel said dur­ing the call. One op­tion is a third dose of mR­NA -1273. But the biotech is al­so test­ing a new strain-spe­cif­ic boost­er, dubbed mR­NA-1273.351, in pre­clin­i­cal stud­ies and a Phase I tri­al in the US.

CMO Tal Zaks said he ex­pects the orig­i­nal reg­i­men will be pro­tec­tive in the near term, even against the South Africa vari­a­tion. A third boost­er shot like­ly wouldn’t be nec­es­sary un­til six to 12 months af­ter the pri­ma­ry se­ries is giv­en, he said.

In ad­di­tion, Mod­er­na says its boost­er shot (both mR­NA-1273 and mR­NA-1273.351) could po­ten­tial­ly boost im­mune re­sponse “in com­bi­na­tion with all of the lead­ing vac­cine can­di­dates.”

“As we pub­lished in the past, our vac­cine is very good at de­vel­op­ing and boost­ing those titers,” Hoge said dur­ing the call. “And we be­lieve an mR­NA vac­cine, or po­ten­tial­ly a third dose of an mR­NA vac­cine, is a way that if it be­comes nec­es­sary in the fu­ture, we can raise those titers again. And that’s par­tic­u­lar­ly im­por­tant as we think about, over time, wan­ing or de­creas­ing im­mu­ni­ty, specif­i­cal­ly to some of these new emerg­ing strains.” — Nicole De­Feud­is

Italy and Swe­den call Pfiz­er out for vac­cine dis­tri­b­u­tion trou­bles

As Pfiz­er’s vac­cine de­liv­er­ies run be­hind sched­ule in the EU and ques­tions linger about how much to charge for each vial, two dis­sat­is­fied coun­tries are stand­ing up to the big phar­ma.

Italy is once again threat­en­ing le­gal ac­tion over ship­ment de­lays that are af­fect­ing the coun­try’s vac­cine roll­out, Reuters re­port­ed. On Mon­day, the gov­ern­ment sent a for­mal let­ter of no­tice to Pfiz­er, urg­ing them to com­ply with con­trac­tu­al com­mit­ments for vac­cine de­liv­ery.

Last week, the Wall Street Jour­nal re­port­ed that Pfiz­er’s ship­ment was cut by 29%. Pfiz­er and BioN­Tech had warned the EU and Cana­da ear­li­er this month to ex­pect few­er dos­es as they up­grade their Bel­gium fac­to­ry. But Italy has said it doesn’t ap­pre­ci­ate the short no­tice.

Pfiz­er could be ac­cused of breach­ing its con­tract with the EU if it doesn’t meet con­trac­tu­al oblig­a­tions for vac­cine de­liv­ery, Reuters re­port­ed. And Prime Min­is­ter Giuseppe Con­te said the coun­try is pre­pared to use all avail­able le­gal tools, ac­cord­ing to the news agency.

Swe­den is with­hold­ing its pay­ments to Pfiz­er, af­ter the last billing state­ment raised some eye­brows. Pfiz­er charged the coun­try for six dos­es per vial, in­stead of five like it ini­tial­ly agreed, Reuters re­port­ed. 

Ear­li­er this month, the EU found that it was pos­si­ble to squeeze out a sixth dose be­cause of over­fill­ing. But there’s a catch: With­out a spe­cial sy­ringe, those ad­min­is­ter­ing the vac­cine can’t quite get that sixth dose out. Now Swe­den is call­ing on the EU Com­mis­sion and Pfiz­er to agree on how many dos­es can re­al­ly be ex­tract­ed.

“This is un­ac­cept­able. If a coun­try on­ly has the abil­i­ty to ex­tract five dos­es, it has re­ceived few­er dos­es for the same price,” Swe­den’s vac­cine co­or­di­na­tor Richard Bergstrom told the dai­ly news­pa­per Da­gens Ny­heter, per Reuters.

Un­til the is­sue is re­solved, Swe­den’s health agency is hold­ing on­to its pay­ments — and the re­ceipts. — Nicole De­Feud­is

Sh­iono­gi out­li­cens­es DP1 treat­ment to BioAge in US and Eu­rope

Japan­ese drug­mak­er Sh­iono­gi has sold rights to a Covid-19 treat­ment to BioAge Labs, a biotech in Cal­i­for­nia.

The ex­per­i­men­tal drug, dubbed BGE-175, was orig­i­nal­ly de­vel­oped to treat al­ler­gic rhini­tis by in­hibit­ing the DP1 re­cep­tor, and it has been test­ed in over 2,400 pa­tients thus far, Sh­iono­gi said Tues­day. But its ap­par­ent abil­i­ty to en­hance im­mune func­tion sug­gests it could prove use­ful in Covid-19 as well.

A study at the Uni­ver­si­ty of Iowa al­so in­di­cat­ed that an ex­ist­ing DP1 an­tag­o­nist proved ef­fec­tive in treat­ing the coro­n­avirus re­spon­si­ble for the 2003 SARS epi­dem­ic in a mouse mod­el. The pair be­came aware of the tar­get af­ter an AI analy­sis con­duct­ed by BioAge in­di­cat­ed its po­ten­tial, Sh­iono­gi said.

With the deal, Sh­iono­gi will re­ceive an undis­closed up­front pay­ment as well as po­ten­tial mile­stones and roy­al­ties. BioAge, mean­while, will be able to mar­ket any fin­ished Covid-19 prod­uct in the US and Eu­rope and ob­tain ex­clu­sive bar­gain­ing rights to ex­pand the deal in­to ad­di­tion­al in­di­ca­tions.

BioAge is ex­pect­ed to launch Phase II tri­als in Covid-19 with­in the first half of 2021.

Sh­iono­gi is al­so de­vel­op­ing a re­com­bi­nant pro­tein vac­cine for Covid-19 that is now in com­bined Phase I and II tri­als in Japan. — Max Gel­man

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

CRLs. 483s. CBER, CDER and RWE. For biopharma professionals, these acronyms command attention because of the fundamental role FDA plays in drug development. Now Endpoints is doubling down on regulatory coverage, and launching a weekly report focusing on developments out of White Oak, with analysis and insight into what it all means.

Coverage will be led by our new senior editor, Zachary Brennan. He joins Endpoints from POLITICO, where he covered pharma. Prior to that he was the managing editor for Regulatory Focus, a news publication from the Regulatory Affairs Professionals Society.

Merck spent $425 million to buy out OncoImmune in November, presumably under the belief that they could scale up their drug for severe Covid-19 and get it through the FDA on the strength of a Phase III trial the smaller biotech completed in September.

The FDA threw a wrench in those plans. The agency told Merck last week that the 203-person study wasn’t sufficient to show the drug was effective. Now, Bloomberg reports, Merck is preparing an additional Phase III study, one that will push results — and any chance of approval — back to the end of the year.