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.”

A new era of treat­ment: How bio­mark­ers are chang­ing the way we think about can­cer

AJ Patel was recovering from a complicated brain surgery when his oncologist burst into the hospital room yelling, “I’ve got some really great news for you!”

For two years, Patel had been going from doctor to doctor trying to diagnose his wheezing, only to be dealt the devastating news that he had stage IV lung cancer and only six months to live. And then they found the brain tumors.

“What are you talking about?” Patel asked. He had never seen an oncologist so happy.

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Adam Russell, ARPA-H's incoming acting deputy director

NI­H's new, in­de­pen­dent break­through drug ac­cel­er­a­tor ARPA-H gets its first em­ploy­ee

Despite the controversy of housing it in NIH, HHS Secretary Xavier Becerra on Wednesday afternoon formally announced the establishment of the Advanced Research Project Agency for Health (ARPA-H) as an independent entity within the NIH, as HHS had previously stipulated that “NIH may not subject ARPA-H to NIH policies.”

Becerra also announced the appointment of ARPA-H’s inaugural employee, Adam Russell, who will serve as acting deputy director.

Up­dat­ed: US sees spike in Paxlovid us­age as Mer­ck­'s mol­nupi­ravir and As­traZeneca's Evusheld are slow­er off the shelf

New data from HHS show that more than 162,000 courses of Pfizer’s Covid-19 antiviral Paxlovid were administered across the US over the past week, continuing a streak of increased usage of the pill, and signaling not only rising case numbers but more awareness of how to access it.

In comparison to this week, about 670,000 courses of the Pfizer pill have been administered across the first five months since Paxlovid has been on the US market, averaging about 33,000 courses administered per week in that time.

FDA spells out the rules and re­stric­tions for states seek­ing to im­port drugs from Cana­da

The FDA is offering more of an explanation of the guardrails around its program that may soon allow states to import prescription drugs in some select circumstances from Canada, but only if such imports will result in significant cost reductions for consumers.

While the agency has yet to sign off on any of the 5 state plans in the works so far, and PhRMA’s suit to block the Trump-era rule allowing such imports is stalled, the new Q&A guidance spells out the various restrictions that states will have to abide by, potentially signaling that a state approval is coming.

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Flag­ship's lat­est biotech could turn some of the thou­sands of new pro­teins it dis­cov­ered in­to ther­a­pies — and it has $75M to start

Flagship Pioneering, the incubator of Moderna and dozens of other biotechs, says it has landed upon tens of thousands of previously undiscovered human proteins. The VC shop wants to potentially turn them into therapeutics.

Like other drug developers that have turned proteins into therapeutics (think insulin for diabetes), Flagship’s latest creation, ProFound Therapeutics, wants to tap into this new trove of proteins as part of its mission to treat indications ranging from rare diseases to cancer to immunological diseases.

Richard Silverman, Akava Therapeutics founder and Northwestern professor

This time around, Lyri­ca's in­ven­tor is de­vel­op­ing his North­west­ern dis­cov­er­ies at his own biotech

Richard Silverman was left in the dark for the last five years of clinical development of the drug he discovered. The Northwestern University professor found out about the first approval of Lyrica, in the last few days of 2004, like most other people: in the newspaper.

What became one of Pfizer’s top-selling meds, at $5 billion in 2017 global sales before losing patent protection in 2019, started slipping out of his hands when Northwestern licensed it out to Parke-Davis, one of two biotechs that showed interest in developing the drug in the pre-email days, when the university’s two-person tech transfer team had to ship out letters to garner industry appetite.

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Mihael Polymeropoulos, Vanda Pharmaceuticals CEO

Phar­ma com­pa­ny con­tin­ues its FDA law­suit spree, this time af­ter agency de­nies fast-track des­ig­na­tion

Vanda Pharmaceuticals is making a name for itself, at least in terms of suing the FDA.

The DC-headquartered firm on Monday filed its latest suit against the agency, with the company raising concerns over the FDA’s failure to grant a fast track designation for Vanda’s potential chronic digestive disorder drug tradipitant, which is a neurokinin 1 receptor antagonist.

Specifically, Vanda said FDA’s “essential point” in its one-page denial letter on the designation pointed to “the lack of necessary safety data,” which was “inconsistent with the criteria for … Fast Track designation.”

Mod­er­na seeks to dis­miss Al­ny­lam suit over Covid-19 vac­cine com­po­nent, claim­ing wrong venue

RNAi therapeutics juggernaut Alnylam Pharmaceuticals made a splash in March when it sued and sought money from both Pfizer and Moderna regarding their use of Alnylam’s biodegradable lipids, which Alnylam claims have been integral to the way both companies’ mRNA-based Covid-19 vaccines work.

But now, Moderna lawyers are firing back, telling the same Delaware district court that Alnylam’s claims can only proceed against the US government in the Court of Federal Claims because of the way the company’s contract is set up with the US government. The US has spent almost $10 billion on Moderna’s Covid-19 vaccine so far.

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David Ricks, Eli Lilly CEO (David Paul Morris/Bloomberg via Getty Images)

Eli Lil­ly set to in­vest $2.1B in home state man­u­fac­tur­ing boost

Eli Lilly is looking to expand its footprint in its home Hoosier State by making a major investment in manufacturing.

The pharma is investing $2.1 billion in two new manufacturing sites at Indiana’s LEAP Lebanon Innovation and Research District in Boone County, northwest of Lilly’s headquarters in Indianapolis.

The two new facilities will expand Lilly’s manufacturing network for active ingredients and new therapeutic modalities, including genetic medicines, according to a press release.

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