Anthony Fauci, NIAID director (AP Images)

As new Covid-19 task force gets un­der­way, threat looms of vac­cine, mon­o­clon­al an­ti­body-re­sis­tant vari­ants

Hours be­fore Pres­i­dent Biden’s Covid-19 team gave their first vir­tu­al press con­fer­ence, the famed AIDS re­searcher David Ho de­liv­ered con­cern­ing news in a new pre-print: SARS-CoV-2 B.1.351, the vari­ant that emerged in South Africa, is “marked­ly more re­sis­tant” to an­ti­bod­ies from con­va­les­cent plas­ma and vac­ci­nat­ed in­di­vid­u­als.

The news for sev­er­al mon­o­clon­al an­ti­bod­ies, in­clud­ing Eli Lil­ly’s bam­lanivimab, was even worse: Their abil­i­ty to neu­tral­ize was “com­plete­ly or marked­ly abol­ished,” Ho wrote. Lil­ly’s an­ti­body cock­tail, which was just shown to dra­mat­i­cal­ly re­duce the risk of hos­pi­tal­iza­tions or death, al­so be­came far less po­tent.

The B1.351 vari­ant has yet to be seen in the US, new CDC di­rec­tor Rochelle Walen­sky as­sured re­porters, but the vari­ants nonethe­less took up a sub­stan­tial por­tion of the first Covid-19 brief­ing, as Walen­sky and NI­AID di­rec­tor An­tho­ny Fau­ci out­lined steps the US would take as they be­came more com­mon in the coun­try and as the virus con­tin­ues to mu­tate, po­ten­tial­ly in ways that make them yet more re­sis­tant to vac­cines and an­ti­bod­ies.

The B.1.1.7 vari­ant, now dom­i­nant in the UK and grow­ing in the US, hasn’t been able to sig­nif­i­cant­ly elide vac­cines or mon­o­clon­al an­ti­bod­ies, Fau­ci said. There’s grow­ing ev­i­dence, though, that the vari­ant com­mon in South Africa can avoid mon­o­clon­als and some an­ti­bod­ies pro­duced by vac­cines.

Be­cause the Pfiz­er and Mod­er­na vac­cines are so ef­fec­tive, Fau­ci said, po­ten­cy can drop con­sid­er­ably with­out im­pact­ing ef­fi­ca­cy, and there are no da­ta to sug­gest the vac­cine isn’t still pro­tec­tive.

“How­ev­er,” he said, “giv­en that as a fact now, we have to be con­cerned about what fur­ther evo­lu­tion of this might be.”

So far, the on­ly tests for whether vac­cines and mon­o­clon­al an­ti­bod­ies can neu­tral­ize new vari­ants have been in vit­ro stud­ies — test tube ex­per­i­ments where the an­ti­bod­ies are mixed with a fake ver­sion of SARS-CoV-2 the ex­per­i­menter checks to see whether the virus still man­aged to in­fect cells. Those ex­per­i­ments, con­duct­ed both by com­pa­nies and in aca­d­e­m­ic labs, have been en­cour­ag­ing for B.1.1.7 and dis­cour­ag­ing for B.1.351.

The new Ho pa­per, for ex­am­ple, con­duct­ed in col­lab­o­ra­tion with the NIH and Re­gen­eron, showed 10 out of 12 an­ti­bod­ies were equal­ly ef­fec­tive against B.1.1.7 and two were on­ly slight­ly less ef­fec­tive, while vac­cine ef­fi­ca­cy fell 2-fold. The B.1.351 vari­ant, though, al­most en­tire­ly avoid­ed five of the mon­o­clon­al an­ti­bod­ies, while vac­cine ef­fi­ca­cy fell 6.5-fold for Pfiz­er and 8.6-fold for Mod­er­na.

Soon, though, the US is like­ly to get da­ta on how the vac­cine works against the dif­fer­ent vari­ants in the re­al world, Fau­ci said. J&J con­duct­ed their piv­otal vac­cine tri­al around the world, in­clud­ing in South Africa and Brazil, where an­oth­er vari­ant, called P.1, has spread. Their re­sults should come “with­in the next few days,” Fau­ci said.

“What we will see was the rel­a­tive ef­fi­ca­cy against the wild type virus that is pre­dom­i­nant­ly in the US, as well as the South African iso­late,” Fau­ci said. It “will in­form us of where we would go, if the even­tu­a­tion oc­curs that we do have that par­tic­u­lar lin­eage seed it­self in the Unit­ed States.”

In the mean­time, vac­cine and an­ti­body de­vel­op­ers have been prepar­ing for that po­ten­tial. Mod­er­na de­vel­oped a vac­cine de­signed specif­i­cal­ly for B.1.351 and has said they will start Phase I tri­als us­ing both the new vac­cine and the orig­i­nal as a boost­er shot. Pfiz­er and No­vavax said they are al­so draw­ing up con­tin­gency plans.

The Ho pa­per point­ed an­ti­body de­vel­op­ers, who are more acute­ly threat­ened by a mu­tat­ing virus than vac­cine com­pa­nies, to a po­ten­tial so­lu­tion. Al­though Eli Lil­ly’s main an­ti­body did lit­tle against the new vari­ant, Re­gen­eron’s com­bo still suc­cess­ful­ly neu­tral­ized it, point­ing to the po­ten­tial im­por­tance of com­bi­na­tion strate­gies.

Still, a com­bo isn’t nec­es­sar­i­ly a panacea, as shown by the low po­ten­cy Ho found for Lil­ly’s cock­tail. The In­di­anapo­lis-based Big Phar­ma an­nounced this morn­ing, though, that they be­gan ex­per­i­men­tal­ly dos­ing pa­tients with a com­bi­na­tion of bam­lanivimab and an an­ti­body Vir and GSK are co-de­vel­op­ing. In a state­ment, GSK not­ed that the two an­ti­bod­ies bind to dif­fer­ent epi­topes, or sub-units, of the virus.

Vir could al­so emerge as a win­ner in the hunt for an ef­fec­tive sin­gle an­ti­body. Re­ly­ing on an an­ti­body that al­so neu­tral­izes the orig­i­nal SARS virus, they long po­si­tioned them­selves as de­vel­op­ing the best an­ti­body should the virus mu­tate. Al­though their po­ten­cy was re­duced against B.1.351, it still ef­fec­tive­ly neu­tral­ized the vari­ant. A large tri­al of the an­ti­body is due to read out in the com­ing weeks.

Re­spond­ing to the new strains, how­ev­er, will re­quire the US to prop­er­ly mon­i­tor the genomes of virus­es en­ter­ing the coun­try and to track how the virus evolves with­in the coun­try. So far, the US has lagged con­sid­er­ably in se­quenc­ing virus­es, of­fi­cials ac­knowl­edged at the brief­ing, rank­ing 43rd in the world ac­cord­ing to one count.

The new health of­fi­cials promised that would im­prove, not­ing that Biden’s new stim­u­lus and re­lief bill in­cludes funds for ge­nom­ic sur­veil­lance.

“It is es­sen­tial as part of the Amer­i­can res­cue plan,” said Jef­frey Zients, co­or­di­na­tor of Biden’s Covid-19 re­sponse.

Fau­ci added that se­quenc­ing will be sup­ple­ment­ed with con­tin­u­al stud­ies to test whether an­ti­bod­ies from vac­cines neu­tral­ize new vari­ants and when it’s time to push for­ward mod­i­fied vac­cines or an­ti­bod­ies.

“All of that is go­ing on,” he said, “lit­er­al­ly as we speak.”

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

Bob Nelsen (Photo by Michael Kovac/Getty Images)

With stars aligned and cash in re­serve, Bob Nelsen's Re­silience plans a makeover at 2 new fa­cil­i­ty ad­di­tions to its drug man­u­fac­tur­ing up­start

Bob Nelsen’s new, state-of-the-art drug manufacturing initiative is taking shape.

Just 3 months after gathering $800 million of launch money, a dream team board and a plan to shake up a field where he found too many bottlenecks and inefficiencies for the era of Covid-19, Resilience has snapped up a pair of facilities now in line for a retooling.

The company has acquired a 310,000-square-foot plant in Boston from Sanofi along with a 136,000-square-foot plant in Ontario to add to a network which CEO Rahul Singhvi says is just getting started on building his company’s operations up. The Sanofi deal comes with a contract to continue manufacturing one of its drugs.

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Af­ter bail­ing on Covid-19 vac­cines, Mer­ck will team up with J&J to pro­duce its shot as part of un­usu­al Big Phar­ma pact

Merck took a big gamble when it opted to jump into the Covid-19 vaccine race late, and made an equally momentous decision to back out in late January. Now, looking to chip in on the effort, Merck reportedly agreed to team up with one of the companies that has already crossed the finish line.

President Joe Biden on Tuesday is expected to announce a partnership between drugmakers Merck and Johnson & Johnson to jointly produce J&J’s recombinant protein Covid-19 vaccine that received the FDA’s emergency use authorization Saturday, the Washington Post reported.

UP­DAT­ED: Mer­ck pulls Keytru­da in SCLC af­ter ac­cel­er­at­ed nod. Is the FDA get­ting tough on drug­mak­ers that don't hit their marks?

In what could be an early shot in the battle against drugmakers that whiff on confirmatory studies to support accelerated approvals, the FDA ordered Bristol Myers Squibb late last year to give up Opdivo’s approval in SCLC. Now, Merck is next on the firing line — are we seeing the FDA buckling down on post-marketing offenders?

Merck has withdrawn its marketing approval for PD-(L)1 inhibitor Keytruda in metastatic small cell lung cancer as part of what it describes as an “industry-wide evaluation” by the FDA of drugs that do not meet the post-marketing checkpoints on which their accelerated nods were based, the company said Monday.

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Pascal Soriot, AstraZeneca CEO (AP Images)

Pas­cal So­ri­ot cash­es in As­traZeneca’s chips on Mod­er­na for $1.2B cash in­jec­tion

While still working to prove its own Covid-19 vaccine, AstraZeneca has reportedly capitalized on the success of another.

The company has sold off its 7.7% stake in Moderna and turned it into $1.2 billion in cash, according to the Times, beefing up the reserves just as Pascal Soriot is wrapping up his $39 billion acquisition of Alexion and its rare disease pipeline.

AstraZeneca’s stock sale follows a similar move by Merck in December. But like its pharma brethren, the British giant is keeping its R&D collaborations with Moderna.

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Amit Munshi, Arena

One of Are­na's top drugs flops in a PhI­Ib study for IBS pain. But re­searchers tease out a pos­si­ble path for­ward as CEO ex­plores 's­trate­gic op­tion­s'

Four years ago, when Arena CEO Amit Munshi cut its ties to a troubled weight drug and doubled down on the pipeline, a cannabinoid receptor 2 agonist figured prominently in the biotech’s future. On Tuesday evening, however, Munshi’s high hopes for the drug took a nasty hit after it failed a Phase IIb study for patients with irritable bowel syndrome pain.

Put through a randomized pace with 273 patients, researchers said it flat failed the primary endpoint among the large group with abdominal pain. But they quickly went on to highlight subgroup data, always a tricky and controversial ploy, where they spotlighted a positive p value for patients with moderate to severe pain who received the high dose of the drug — one of 3 provided in the study.

UP­DAT­ED: Feds clear the road for J&J to start de­liv­er­ing mil­lions of dos­es of their Covid-19 vac­cine — but frets linger about run­ner-up sta­tus

All the pieces needed to trigger a third wave of Covid-19 vaccine supply to start washing over the US fell neatly into place over the weekend.

After providing for a brief mime of regulatory judiciousness, the FDA stamped their emergency approval on J&J’s Covid-19 vaccine Saturday, adding to the Biden administration’s plan aimed at ending the pandemic in the near term — at least in the US. The CDC came through on Sunday with its stamp of approval and J&J is reportedly expected to start delivering vaccine sometime in the next few days.

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Ab­b­Vie tees up a biotech buy­out af­ter siz­ing up their Parkin­son's drug spun out of Ke­van Shokat's lab

AbbVie has teed up a small but intriguing biotech buyout after looking over the preclinical work it’s been doing in Parkinson’s disease.

The company is called Mitokinin, a Bay Area biotech spun out of the lab of UCSF’s Kevan Shokat, whose scientific explorations have formed the academic basis of a slew of startups in the biotech hub. One of Shokat’s PhD students in the lab, Nicholas Hertz, co-founded Mitokinin using their lab work on PINK1 suggesting that amping up its activity could play an important role in regulating the mitochondrial dysfunction contributing to Parkinson’s disease pathogenesis and progression.

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Paul Sekhri

The next big biotech su­per­star? Paul Sekhri has some thoughts on that

It occasionally occurs to Paul Sekhri that if they pull this off, his company will be on the front page of the New York Times and a lead story in just about every major news outlet on the planet. He tries not to dwell on it, though.

“I just want to be laser-focused on getting to that point,” Sekhri says, before acknowledging, “Yes, it absolutely crossed my mind.”

Sekhri, a longtime biopharma executive with tenures at Sanofi and Novartis, is now entering year three as CEO of eGenesis, the biotech that George Church protégé Luhan Yang founded to genetically alter pigs so that they can be used for organ transplants. He led them through one megaround and has just closed another, raising $125 million from 17 different investors to push the first-ever (humanized) pig to human transplants into the clinic.

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Fi­bro­Gen shares skid low­er as a sur­prise ad­comm rais­es risks on roxa OK

FibroGen will likely have to delay its US rollout for roxadustat once again.

In an unexpected move, the FDA is convening its Cardiovascular and Renal Drugs Advisory Committee to review the NDA in an advisory committee meeting. The date is yet to be confirmed.

Just a few weeks ago, SVB Leerink analyst Geoffrey Porges predicted that the roxa approval could come ahead of the PDUFA date on March 20 — effusive despite already being let down once by the FDA’s extension of its review back in December. AstraZeneca, which is partnered with FibroGen on the chronic kidney disease-related anemia drug, disclosed regulators had requested further clarifying analyses of clinical data.