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.”

How one start­up fore­told the neu­ro­science re­nais­sance af­ter '50 years of shit­show'

In the past couple of years, something curious has happened: Pharma and VC dollars started gushing into neuroscience research.

Biogen’s controversial new Alzheimer’s drug Aduhelm has been approved on the basis of removing amyloid plaque from the brain, but the new neuro-focused pharma and biotechs have much loftier aims. Significantly curbing or even curing the most notorious disorders would prove the Holy Grail for a complex system that has tied the world’s best drug developers in knots for decades.

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Bob Bradway, Amgen CEO (Scott Eisen/Bloomberg via Getty Images)

Am­gen bel­lies back up to the M&A ta­ble for an­oth­er biotech buy­out, this time with a $2.5B deal for an an­ti­body play­er fo­cused on PS­MA

Five months after Amgen CEO Bob Bradway stepped up to the M&A table and acquired Five Prime for $1.9 billion, following up with the smaller Rodeo acquisition, he’s gone back in for another biotech buyout.

This time around, Amgen is paying $900 million cash while committing up to $1.6 billion in milestones to bag the privately held Teneobio, an antibody drug developer that has expertise in developing new bispecifics and multispecifics. In addition, Amgen cited Teneobio’s “T-cell engager platform, which expands on Amgen’s existing leadership position in bispecific T-cell engagers by providing a differentiated, but complementary, approach to Amgen’s current BiTE platform.”

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Busi­ness­es and schools can man­date the use of Covid-19 vac­cines un­der EUAs, DOJ says

As public and private companies stare down the reality of the Delta variant, many are now requiring that their employees or students be vaccinated against Covid-19 prior to attending school or to returning or starting a new job. Claims that such mandates are illegal or cannot be used for vaccines under emergency use authorizations have now been dismissed.

Setting the record straight, the Department of Justice on Monday called the mandates legal in a new memo, even when used for people with vaccines that remain subject to EUAs.

Ryan Watts, Denali CEO

De­nali slips as a snap­shot of ear­ly da­ta rais­es some trou­bling ques­tions on its pi­o­neer­ing blood-brain bar­ri­er neu­ro work

Denali Therapeutics had drummed up considerable hype for their blood-brain barrier technology since launching over six years ago, hype that’s only intensified in the last 14 months following the publications of a pair of papers last spring and proof of concept data earlier this year. On Sunday, the South San Francisco-based biotech gave the biopharma world the next look at in-human data for its lead candidate in Hunter syndrome.

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Why is On­col­o­gy Drug De­vel­op­ment Re­search Late to the Dig­i­tal Bio­mark­ers Game?

During the recent Annual ASCO Meeting, thousands of cancer researchers and clinicians from across the globe joined together virtually to present and discuss the latest findings and breakthroughs in cancer research and care. There were more than 5000+ scientific abstracts presented during this event, yet only a handful involved the use of motion-tracking wearables to collect digital measures relating to activity, sleep, mobility, functional status, and/or quality of life. Although these results were a bit disappointing, they should come as no surprise to those of us in the wearable technology field.

Art Levinson (Calico)

Google-backed Cal­i­co dou­bles down on an­ti-ag­ing R&D pact with Ab­b­Vie as part­ners ante up $1B, start to de­tail drug tar­gets

Seven years after striking up a major R&D alliance, AbbVie and Google-backed anti-aging specialist Calico are doubling down on their work with a joint, $1 billion commitment to continuing their work together. And they’re also beginning to offer some details on where this project is taking them in the clinic.

According to their statement, each of the two players is putting up $500 million more to keep the labs humming.

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UP­DAT­ED: Pan­el of neu­ro­science ex­perts lays out the com­pli­ca­tions with us­ing Bio­gen's new Alzheimer's drug

Treatment of early Alzheimer’s patients with Biogen’s new drug Aduhelm should closely resemble how the drug was studied in its pivotal clinical trials, according to new recommendations from a panel of neuroscience experts led by UNLV’s Jeffrey Cummings.

“Those considering aducanumab therapy should understand that the expected benefit is slowing of cognitive and functional decline; improvement of the current clinical state is not anticipated,” they wrote Tuesday in The Journal of Prevention of Alzheimer’s Disease, noting that some of their recommendations are more specific or more restrictive than the information provided in the FDA’s prescribing information.

Covid-19 roundup: Till­man Gern­gross inks deal to bring an­ti­body can­di­date to In­dia; At FDA's re­quest, mR­NA vac­cine mak­ers will ex­pand tri­als for chil­dren ages 5-11

A week after it was reported that India’s Covid-19 death toll could be in the millions, antibody legend Tillman Gerngross has inked a deal to develop Adagio’s lead candidate for the treatment and prevention of the virus in southern Asia.

Adagio is joining hands with Biocon Biologics to manufacture and commercialize a treatment based on ADG20 in India and “select emerging markets,” the companies announced on Monday. Under the agreement, Adagio will provide Biocon with materials and know-how to make the therapy, including data from ongoing Phase II/III trials and (if all goes well) access to its potential EUA package.

Ugur Sahin, BioNTech CEO (Bernd von Jutrczenka/dpa via AP Images)

BioN­Tech is spear­head­ing an mR­NA vac­cine de­vel­op­ment pro­gram for malar­ia, with a tech trans­fer planned for Africa

Flush with the success of its mRNA Covid-19 vaccine, BioNTech is now gearing up for one of the biggest challenges in vaccine development — which comes without potential profit.

The German mRNA pioneer says it plans to work on a jab for malaria, then transfer the tech to the African continent, where it will work with partners on developing the manufacturing ops needed to make this and other vaccines.

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