Ugur Sahin, BioNTech CEO (Frank Rumpenhorst/dpa via AP Images)

New stud­ies in­di­cate mR­NA vac­cines pro­vide lim­it­ed pro­tec­tion against Omi­cron, but boost­ers and new shots may be cru­cial

The first sub­stan­tial ev­i­dence for how mR­NA vac­cines will hold up against the new Omi­cron vari­ant was re­leased Tues­day night from sci­en­tists in South Africa.

The study, con­duct­ed by mix­ing sera from vac­ci­nat­ed in­di­vid­u­als with live Omi­cron virus, showed that the vari­ant could large­ly — but not en­tire­ly — dodge an­ti­bod­ies elicit­ed by the Pfiz­er-BioN­Tech vac­cine.

The re­sult sug­gests that the vac­cines will be less ef­fec­tive at pre­vent­ing in­fec­tion by Omi­cron. But be­cause many an­ti­bod­ies do still bind to the virus, ex­perts say, boost­ers should help stem the de­cline. And ef­fi­ca­cy will like­ly hold up against the most im­por­tant met­ric for vac­cines: pre­vent­ing se­vere dis­ease.

On Wednes­day morn­ing, Pfiz­er added its own ear­ly da­ta from in­ter­nal stud­ies, echo­ing the re­sults from South Africa while pro­vid­ing ev­i­dence that boost­ers can im­prove ef­fi­ca­cy.

“The im­por­tant ques­tion is whether vac­cines will main­tain ef­fi­ca­cy against se­vere dis­ease, mean­ing dis­ease that will cause you go to the doc­tor or a hos­pi­tal” Paul Of­fit, di­rec­tor of the Vac­cine Ed­u­ca­tion Cen­ter at Chil­dren’s Hos­pi­tal of Philadel­phia, told End­points News. “And I think the an­swer to that is in all like­li­hood yes.”

Flo­ri­an Kram­mer, a vac­ci­nol­o­gist at Mt. Sinai School of Med­i­cine, chimed in on Twit­ter, say­ing “Pro­tec­tion against se­vere dis­ease may re­main rea­son­ably high in all in­di­vid­u­als with base­line im­mu­ni­ty,” though he cau­tioned it “was spec­u­la­tion.”

Caveats about the ear­ly da­ta abound. The study, led by Alex Si­gal, a vi­rol­o­gist at the Africa Health Re­search In­sti­tute in Dur­ban, South Africa, on­ly looked at the ef­fi­ca­cy of an­ti­bod­ies from six peo­ple who had re­ceived two dos­es of the Pfiz­er shot. They found a 41-fold re­duc­tion in neu­tral­iza­tion com­pared to pre­vi­ous ver­sions of the virus.

In peo­ple who have re­ceived three dos­es, the quan­ti­ty of the an­ti­bod­ies may com­pen­sate for some of the re­duced qual­i­ty. In­deed, Pfiz­er said its own da­ta con­firmed re­duced ef­fi­ca­cy for those who re­ceived two dos­es. But the com­pa­ny not­ed it found sera from in­di­vid­u­als who re­ceived boost­ers one month pri­or can still neu­tral­ize the virus.

It re­mains un­clear, though, how long that in­creased pro­tec­tion lasts, Walid Gel­lad, di­rec­tor of the Uni­ver­si­ty of Pitts­burgh Cen­ter for Phar­ma­ceu­ti­cal Pol­i­cy and Pre­scrib­ing, said on Twit­ter. An­ti­body lev­els tend to climb sub­stan­tial­ly af­ter every dose but then fall off.

An­ti­bod­ies are on­ly one part of a com­plex and mul­ti-pronged im­mune re­sponse. They are par­tic­u­lar­ly af­fect­ed by the new vari­ant and its 30 spike pro­tein mu­ta­tions be­cause to be ef­fec­tive, they need to latch on­to the spike, at which point they ei­ther block its func­tion or re­cruit oth­er im­mune cells to gob­ble the virus.

T cells, though, don’t need to bind to the spike. They seek out in­fect­ed cells, in­duc­ing any they rec­og­nize to self-de­struct. Re­searchers ex­pect these will re­main ef­fec­tive against the vari­ant, help­ing pro­tect vac­ci­nat­ed in­di­vid­u­als from se­vere dis­ease.

In its state­ment, Pfiz­er said that 80% of spike epi­topes — re­gions, ba­si­cal­ly — rec­og­nized by killer T cells are not af­fect­ed by Omi­cron’s mu­ta­tions. Of­fit not­ed these cells have main­tained ef­fi­ca­cy against every vari­ant through­out the pan­dem­ic.

Nev­er­the­less, these da­ta sug­gest that Mod­er­na and Pfiz­er should con­tin­ue de­vel­op­ing an Omi­cron-spe­cif­ic jab, Fred Hutch vi­rol­o­gist Jesse Bloom told The New York Times.

“Giv­en the very large drop in neu­tral­iz­ing an­ti­body titers that are seen here with Omi­cron,” he said, “cer­tain­ly in my view it would mer­it push­ing for­ward as fast as pos­si­ble with mak­ing Omi­cron-spe­cif­ic vac­cines, as long as it seems like there’s a pos­si­bil­i­ty it could spread wide­ly.”

Pfiz­er, in its state­ment, in­di­cat­ed they were still eval­u­at­ing whether such a shot would be nec­es­sary. But they are work­ing on new se­quences and, if need­ed, those will be ready for tri­als by March.

The ques­tion, Of­fit said, cen­ters around pre­cise­ly what the goal of new shots is. Of­fi­cials can keep rolling out boost­ers, against the orig­i­nal virus or against the Omi­cron vari­ant, to try and stop in­fec­tion or mild dis­ease. But he not­ed of­fi­cials his­tor­i­cal­ly haven’t asked that of vac­cines against flu, ro­tavirus or most oth­er bugs, and he ques­tioned how much of an im­pact such boost­ers, par­tic­u­lar­ly for young peo­ple, would make on the course of the pan­dem­ic.

Vari­ant-spe­cif­ic boost­ers will be need­ed in the un­like­ly event Omi­cron can still cause se­vere dis­ease in vac­ci­nat­ed in­di­vid­u­als, he said. Re­searchers should have more da­ta on that soon.

“I think we should know that with­in weeks,” he said. “If Omi­cron is as con­ta­gious as is claimed, there are a lot of peo­ple out there who have been vac­ci­nat­ed who are go­ing to be in­fect­ed with this virus.”

How those pa­tients fare could give re­searchers the best glimpse yet as to how much a threat Omi­cron is vac­ci­nat­ed. In the mean­time, Of­fit said, the biggest need is to get more peo­ple — in­clud­ing kids — vac­ci­nat­ed for the first time.

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Graphic: Kathy Wong for Endpoints News

What kind of biotech start­up wins a $3B syn­di­cate, woos a gallery of mar­quee sci­en­tists and re­cruits GSK's Hal Bar­ron as CEO in a stun­ner? Let Rick Klaus­ner ex­plain

It started with a question about a lifetime’s dream on a walk with tech investor Yuri Milner.

At the beginning of the great pandemic, former NCI chief and inveterate biotech entrepreneur Rick Klausner and the Facebook billionaire would traipse Los Altos Hills in Silicon Valley Saturday mornings and talk about ideas.

Milner’s question on one of those mornings on foot: “What do you want to do?”

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FDA+ roundup: FDA's neu­ro­science deputy de­parts amid on­go­ing Aduhelm in­ves­ti­ga­tions; Califf on the ropes?

Amid increased scrutiny into the close ties between FDA and Biogen prior to the controversial accelerated approval of Aduhelm, the deputy director of the FDA’s office of neuroscience has called it quits after more than two decades at the agency.

Eric Bastings will now take over as VP of development strategy at Ionis Pharmaceuticals, the company said Wednesday, where he will provide senior clinical and regulatory leadership in support of Ionis’ pipeline.

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CBO: Medicare ne­go­ti­a­tions will ham­per drug de­vel­op­ment more than pre­vi­ous­ly thought

As President Biden’s Build Back Better Act — and, with it, potentially the Democrats’ last shot at major drug pricing reforms in the foreseeable future — remains on life support, the Congressional Budget Office isn’t helping their case.

The CBO last week released a new slide deck, outlining an update to its model on how Medicare negotiations might take a bite out of new drugs making it to market. The new model estimates a 10% long-term reduction in the number of new drugs, whereas a previous CBO report from August estimated that 8% fewer new drugs will enter the market over 30 years.

Joshua Brumm, Dyne Therapeutics CEO

FDA or­ders DMD tri­al halt, rais­ing ques­tions about a whole class of promis­ing drugs

Dyne Therapeutics’ stock took a nasty hit this morning after the biotech put out word that the FDA had slapped a clinical hold on their top program for Duchenne muscular dystrophy. And now speculation is bouncing around Biotwitter that there could be a class effect at work here that would implicate other drug developers in the freeze.

Dyne execs didn’t have a whole lot to say about why the FDA sidelined their IND for DYNE-251 in DMD while “requesting additional clinical and non-clinical information for” the drug.

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Sec­ondary patents prove to be key in biosim­i­lar block­ing strate­gies, re­searchers find

While the US biosimilars industry has generally been a disappointment since its inception, with FDA approving 33 biosimilars since 2015, just a fraction of those have immediately followed their approvals with launches. And more than a handful of biosimilars for two of the biggest blockbusters of all time — AbbVie’s Humira and Amgen’s Enbrel — remain approved by FDA but still have not launched because of legal settlements.

Hal Barron (GSK via YouTube)

GSK R&D chief Hal Bar­ron jumps ship to run a $3B biotech start­up, Tony Wood tapped to re­place him

In a stunning switch, GlaxoSmithKline put out word early Wednesday that R&D chief Hal Barron is exiting the company after 4 years — a relatively brief run for the man chosen by CEO Emma Walmsley in late 2017 to turn around the slow-footed pharma giant.

Barron is being replaced by Tony Wood, a close associate of Barron’s who’s taking one of the top jobs in Big Pharma R&D. He’ll be closer to home, though, for GSK. Barron has been running a UK and Philadelphia-based research organization from his perch in San Francisco.

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Chamath Palihapitiya and Pablo Legorreta

Bil­lion­aires Chamath Pal­i­hapi­tiya and Pablo Legor­re­ta hatch an $825M SPAC for cell ther­a­py biotech

Three years after Royalty Pharma chief Pablo Legorreta led a group of investors to buy up a pair of biotechs and create a new startup called ProKidney, the biotech is jumping straight into an $825 million public shell created by SPAC king and tech billionaire Chamath Palihapitiya.

ProKidney was founded 6 years ago but really got going at the beginning of 2019 with the $62 million acquisition of inRegen, which was working on an autologous — from the patient — cell therapy for kidney disease. After extracting kidney cells from patients, researchers expand the cells in the lab and then inject them back into patients, aiming to restore the kidneys of patients suffering from CKD.

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Michel Vounatsos, Biogen CEO (Credit: World Economic Forum/Ciaran McCrickard)

An un­ortho­dox pro­pos­al for Bio­gen's Medicare-man­dat­ed Aduhelm tri­al

Biogen has gone full blitz since Medicare announced it would only cover its new Alzheimer’s drug when used in clinical trials, accusing the agency of discriminating against Alzheimer’s patients and trying to get physicians to change regulators’ minds.  Critics, meanwhile, cheered what they see as a necessary wall protecting payers and patients from an unproven and unsafe drug.

Far less attention, though, has gone to what a Medicare-funded clinical trial would actually look like. Biogen has operated as if it would be a standard late-stage Alzheimer’s trial, enrolling a couple thousand patients and giving half placebo.

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