FDA commissioner Stephen Hahn at the White House (AP Images)

Un­der fire, FDA to is­sue stricter guid­ance for Covid-19 vac­cine EUA this week — re­port

The FDA has been in­sist­ing for months that a Covid-19 vac­cine had to be at least 50% ef­fec­tive – a mea­sure of trans­paren­cy meant to shore pub­lic trust in the agency and in a vac­cine that had been brought for­ward at record speed and record po­lit­i­cal pres­sure. But now, with con­cerns of a Trump-dri­ven au­tho­riza­tion ar­riv­ing be­fore the elec­tion, the agency may be rais­ing the bar.

The FDA is set to re­lease new guid­ance that would raise safe­ty and ef­fi­ca­cy re­quire­ments for a vac­cine EUA above ear­li­er guid­ance and above the cri­te­ria used for con­va­les­cent plas­ma or hy­drox­y­chloro­quine, The Wash­ing­ton Post re­port­ed. Ex­perts say this sig­nif­i­cant­ly low­ers the odds of an ap­proval be­fore the elec­tion on No­vem­ber 3, which Trump has promised de­spite vo­cal con­cerns from pub­lic health of­fi­cials, and could help shore up pub­lic trust in the agency and any even­tu­al vac­cine.

“This step should help re­as­sure Amer­i­cans that FDA’s ca­reer sci­en­tists with re­spon­si­bil­i­ty for reg­u­lat­ing vac­cines have their back and are mak­ing de­ci­sions based on sound sci­ence,” for­mer FDA chief sci­en­tist Lu­ciana Bo­rio told End­points News in an email, adding they “en­sure that on­ly vac­cines with ad­e­quate safe­ty and mean­ing­ful ef­fec­tive­ness da­ta are grant­ed an EUA.”

Most no­table among the new reg­u­la­tions is a pro­vi­sion that calls for vac­cine man­u­fac­tur­ers seek­ing an EUA fol­low sub­jects for a me­di­an of at least 60 days fol­low­ing the sec­ond dose of the vac­cine. It al­so asks them to ac­crue at least 5 cas­es of se­vere Covid-19 in the place­bo group, a mea­sure that will be sig­nif­i­cant­ly hard­er to hit than the met­rics in the cur­rent tri­al pro­to­cols.

CBER chief Pe­ter Marks had point­ed to some of these mea­sures in pri­or ap­pear­ances, but they were not part of pub­lic guide­lines.

The Post re­port says the guide­lines could come as soon as this week.

Al­though the orig­i­nal FDA guid­ance called for long-term fol­lowup of tri­al par­tic­i­pants, as is rou­tine in vac­cine stud­ies, it did not set a bar for how long vol­un­teers had to be mon­i­tored be­fore de­vel­op­ers filed for an EUA. And while it called for the vac­cine to be 50% ef­fec­tive, the agency left open to man­u­fac­tur­ers whether they would de­fine that as ef­fec­tive in pre­vent­ing in­fec­tion or pre­vent­ing dis­ease.

The new­ly re­leased Phase III pro­to­col for Pfiz­er, whose CEO Al­bert Bourla has been the most vo­cal of any phar­ma­ceu­ti­cal ex­ec­u­tive in promis­ing Covid-19 vac­cine da­ta be­fore No­vem­ber, re­vealed that the com­pa­ny was us­ing a rel­a­tive­ly low bar for ef­fi­ca­cy com­pared to Mod­er­na, count­ing any of a long list of symp­toms as “dis­ease.” Mod­er­na and As­traZeneca al­so did not re­quire in­stances of se­vere dis­ease.

News of the new guide­lines came on the same day that well-known sci­en­tists – al­beit not vac­ci­nol­o­gists – raised con­cerns in The New York Times and The Post opin­ion sec­tions that the cri­te­ria Mod­er­na and Pfiz­er picked were not strin­gent enough. Oth­ers ar­gue bar for ef­fi­ca­cy was al­so in line with WHO guid­ance, al­lows for faster an­swers and is not un­com­mon in vac­cine de­vel­op­ment.

The new guide­lines, though, al­most cer­tain­ly in­crease the amount of time need­ed to de­ter­mine safe­ty and ef­fi­ca­cy.

“It’s hard to imag­ine how an EUA could pos­si­bly oc­cur be­fore De­cem­ber,” Paul Of­fit, a promi­nent vac­ci­nol­o­gist and mem­ber of the FDA’s vac­cines Ad­Comm, told The Post.

Er­ic Topol, who called in The Times for hard­er ef­fi­ca­cy stan­dards and was a crit­ic of the FDA’s con­duct on the EUA for con­va­les­cent plas­ma, praised the move.

Still, it’s not clear who will have fi­nal de­ci­sion mak­ing pow­er on these vac­cines. Ear­li­er this week in a memo panned by one for­mer FDA as­so­ciate com­mis­sion­er as a “pow­er grab,” HHS chief Alex Azar stripped the FDA’s abil­i­ty to make rules with­out his sig­na­ture. An HHS spokesper­son said con­cerns were overblown and called the memo an ex­am­ple of “good gov­er­nance” and had noth­ing to do with vac­cines.

FDA com­mis­sion­er Stephen Hahn, vest­ed with the au­thor­i­ty as fi­nal de­ci­sion mak­er on the na­tion’s drugs, re­ports di­rect­ly to HHS Sec­re­tary Alex Azar. The FDA com­mis­sion­er doesn’t have to fol­low agency ad­vice and it while it would be an ex­tra­or­di­nary breach of prece­dent, ex­perts say the HHS sec­re­tary could is­sue an ap­proval him­self.

Rachel Sachs, a law pro­fes­sor at Wash­ing­ton Uni­ver­si­ty at St Louis, said fed­er­al statutes make clear that the fi­nal de­ci­sion rests with the HHS sec­re­tary, not­ing that in one high-pro­file in­stance dur­ing the Oba­ma Ad­min­is­tra­tion, the sec­re­tary over­ruled FDA com­mis­sion­er Mar­garet Ham­burg on ac­cess rules for “Plan B.” But she called that case the “ex­cep­tion that proves the rule” of the agency’s in­de­pen­dence and said she was skep­ti­cal Azar would over­rule Hahn.

“It would be very dif­fi­cult for the sec­re­tary of HHS to au­tho­rize the vac­cines over ob­jec­tions of FDA, pro­ce­du­ral­ly as well as po­lit­i­cal­ly,” she told End­points News, not­ing Marks’ promise to re­sign if the agency okayed an un­proven vac­cine.

A for­mer FDA of­fi­cial, though, said there’s yet a chance these guide­lines don’t be­come pol­i­cy.  It hasn’t been re­leased and of­fi­cials could yet stop them.

“Want­i­ng to see at least some se­vere cas­es, and want­i­ng 2 months safe­ty da­ta sound like rea­son­able pre­cau­tions,” for­mer FDA chief sci­en­tist Jesse Good­man told End­points in an email. “I am con­cerned that now that this is leaked some­one may try to stop it.”

Qual­i­ty Con­trol in Cell and Gene Ther­a­py – What’s Re­al­ly at Stake?

In early 2021, Bluebird Bio was forced to suspend clinical trials of its gene therapy for sickle cell disease after two patients in the trial developed cancer. As company scientists rushed to assess whether there was any causal link between the therapy and the cancer cases, Bluebird’s stock value plummeted – as did those of multiple other biopharma companies developing similar therapies.

While investigations concluded that the gene therapy was unlikely to have caused cancer, investors and the public may be more skittish regarding the safety of gene and cell therapies after this episode. This recent example highlights how delicate the fields of cell and gene therapy remain today, even as they show great promise.

Sen. Patty Murray (D-WA) (Graeme Sloan/Sipa USA/Sipa via AP Images)

Sen­a­tors to NIH: Do more to pro­tect US bio­med­ical re­search from for­eign in­flu­ence

Although Thursday’s Senate health committee hearing was focused on how foreign countries and adversaries might be trying to steal or negatively influence biomedical research in the US, the only country mentioned by the senators and expert witnesses was China.

Committee chair Patty Murray (D-WA) made clear in her opening remarks that the US cannot “let the few instances of bad actors” overshadow the hard work of the many immigrant researchers in the US, many of which have won Nobel prizes for their work. But she also said, “There is more the NIH can be doing here.”

Covid-19 man­u­fac­tur­ing roundup: Mary­land looks to grow biotech ca­pac­i­ty with $400M check; Rus­sia lands sec­ond Sput­nik V part­ner this week

A Maryland real estate project has added three new biotech-focused manufacturing and research buildings to an office park to keep up with demand created by the pandemic, the Washington Business Journal reported.

The Milestone Business Park — located off of I-270 in Germantown, MD — will see the new buildings and a total of 532,000 square feet as the campus rebrands to Milestone Innovation Park.

Law pro­fes­sors call for FDA to dis­close all safe­ty and ef­fi­ca­cy da­ta for drugs

Back in early 2018 when Scott Gottlieb led the FDA, there was a moment when the agency seemed poised to release redacted complete response letters and other previously undisclosed data. But that initiative never gained steam.

Now, a growing chorus of researchers are finding that a dearth of public data on clinical trials and pharmaceuticals means industry and the FDA cannot be held accountable, two law professors from Yale and New York University write in an article published Wednesday in the California Law Review.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Novavax CEO Stanley Erck at the White House in 2020 (Andrew Harnik, AP Images)

As fears mount over J&J and As­traZeneca, No­vavax en­ters a shaky spot­light

As concerns rise around the J&J and AstraZeneca vaccines, global attention is increasingly turning to the little, 33-year-old, productless, bankruptcy-flirting biotech that could: Novavax.

In the now 16-month race to develop and deploy Covid-19 vaccines, Novavax has at times seemed like the pandemic’s most unsuspecting frontrunner and at times like an overhyped also-ran. Although they started the pandemic with only enough cash to last 6 months, they leveraged old connections and believers into $2 billion and emerged last summer with data experts said surpassed Pfizer and Moderna. They unveiled plans to quickly scale to 2 billion doses. Then they couldn’t even make enough material to run their US trial and watched four other companies beat them to the finish line.

FDA of­fers scathing re­view of Emer­gent plan­t's san­i­tary con­di­tions, em­ploy­ee train­ing af­ter halt­ing pro­duc­tion

The FDA wrapped up its inspection of Emergent’s troubled vaccine manufacturing plant in Baltimore on Tuesday, after halting production there on Monday. By Wednesday morning, the agency already released a series of scathing observations on the cross contamination, sanitary issues and lack of staff training that caused the contract manufacturer to dispose of millions of AstraZeneca and J&J vaccine doses.

Brad Bolzon (Versant)

Ver­sant pulls the wraps off of near­ly $1B in 3 new funds out to build the next fleet of biotech star­tups. And this new gen­er­a­tion is built for speed

Brad Bolzon has an apology to offer by way of introducing a set of 3 new funds that together pack a $950 million wallop in new biotech creation and growth.

“I want to apologize,” says the Versant chairman and managing partner, laughing a little in the intro, “that we don’t have anything fancy or flashy to tell you about our new fund. Same team, around the same amount of capital, same investment strategy. If it ain’t broke, don’t fix it.”

But then there’s the flip side, where everything has changed. Or at least speeded into a relative blur. Here’s Bolzon:

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

In a sup­ply chain short­age workaround, Aus­trali­a's Vic­to­ria state aims to build its own mR­NA fa­cil­i­ty

As countries all around the world have experienced troubles with vaccine shortages, Australia’s Victoria state is developing its own mRNA manufacturing facility in an effort to up its number of vaccinated residents.

Victoria will spend $39 million to set up the facility, which could be the first in the southern hemisphere, Reuters reported. The mRNA technology is used in the Pfizer-BioNTech and Moderna vaccines, and has gotten more attention, as adenovirus-based vaccines from AstraZeneca and J&J have had reports of rare, but similar blood clots in some patients. There have been no reports of major side effects in either Moderna or Pfizer’s jab.

Michel Vounatsos, Biogen CEO (Biogen via YouTube)

Damn the crit­ics, Bio­gen CEO Vounatsos or­ders full speed ahead on prep­ping a con­tro­ver­sial ad­u­canum­ab launch as FDA de­ci­sion looms

Right now one of the most interesting parlor games on Wall Street is offering odds on Biogen’s chances of getting an FDA OK on their controversial Alzheimer’s drug aducanumab.

For most objective players, it looks about like a coin toss, maybe a little worse than 50/50, as the Street balances the bull case of a full, mega blockbuster approval, a restricted approval or a disastrous order to go back to the clinic and mount a new Phase III. That last option was clearly the guidance most of the outside experts in the panel review offered the agency, as the industry is still puzzling out the question of whether or not the FDA is getting tougher in its oversight of drug development.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 107,400+ biopharma pros reading Endpoints daily — and it's free.