President Trump walks past HHS secretary Alex Azar (Getty Images)

Azar falls in line un­der Trump again. Ex­perts say he's re­in­forc­ing a dark sig­nal sent to the FDA

In the lat­est in­ci­dent where Alex Azar has stead­fast­ly tak­en the side of Pres­i­dent Don­ald Trump over that of the FDA, the HHS sec­re­tary was non­com­mit­tal this morn­ing when asked if he sup­ports the at­tempt by his sub­or­di­nates at the FDA to strength­en guide­lines for a vac­cine EUA.

Ap­pear­ing on NBC’s To­day Show, the HHS sec­re­tary mud­died the wa­ters, stat­ing that the guid­ance that mat­ters is the one that is “ac­tu­al­ly al­ready out there.”

His full re­marks:

Alex Azar: The guid­ance that mat­ters is ac­tu­al­ly al­ready out there. We put it out over a month and a half ago at the FDA. What FDA is look­ing at is ac­tu­al­ly just some ad­di­tion­al guide­lines for the man­u­fac­tur­ers who might come in for emer­gency ap­proval, it’s a fair­ly tech­ni­cal doc­u­ment…

Sa­van­nah Guthrie: Do you sup­port it?

Alex Azar: Well we’ll look at it and de­ter­mine if it’s ap­pro­pri­ate but the guid­ance that mat­ters is out there, and FDA’s gonna call these balls and strikes ac­cord­ing to clear stan­dards that FDA has. That is out there, the man­u­fac­tur­ers know what’s ex­pect­ed, the sta­tis­ti­cal re­quire­ments, the safe­ty, the ef­fi­ca­cy.

Hours be­fore Trump took to a White House podi­um yes­ter­day and un­der­cut FDA com­mis­sion­er Stephen Hahn — call­ing the move to strength­en EUA rules as “ex­treme­ly po­lit­i­cal” — Azar was re­port­ed to have spo­ken with the pres­i­dent. Politi­co re­ports the new stan­dards passed muster at HHS on Tues­day and there was an ex­pec­ta­tion that it would get a green light from the White House.

It’s still pos­si­ble Trump gives his bless­ing to Azar to al­low the FDA to is­sue the strin­gent new rules. And some ob­servers note that FDA can tell spon­sors what’s re­quired with­out pub­lish­ing the guid­ance, mak­ing it pub­lic lat­er. But with in­tense glob­al scruti­ny on these tri­als, and the names of the lead­ing vac­cine mak­ers firm­ly im­plant­ed in the pres­i­dent’s lex­i­con, it’s un­like­ly the FDA could do so with­out at­tract­ing Trump’s ire. And with each pass­ing in­ci­dent where Azar clear­ly picks the side of the pres­i­dent over the very pub­lic wish­es of FDA, he risks new episodes that could fur­ther weak­en the agency’s cred­i­bil­i­ty and its abil­i­ty in the eyes of the Amer­i­can pub­lic to vet the safe­ty and ef­fi­ca­cy of Covid-19 vac­cines ar­riv­ing at Warp Speed.

Im­pacts of the Azar memo

This all comes on the heels of Azar’s stun­ning memo last week that stripped the agency of its rule­mak­ing pow­ers, de­clar­ing all of that “is re­served for the Sec­re­tary.” HHS of­fi­cials re­peat­ed­ly claim the memo was sim­ply a mea­sure of “good-gov­er­nance” that would have no im­pact on drugs or vac­cines, but help pro­tect against law­suits.

Ex­perts, though, say that while tech­ni­cal­ly cor­rect, HHS’s state­ment be­lies a more com­pli­cat­ed re­al­i­ty and that their jus­ti­fi­ca­tion for the memo is flim­sy at best.

The memo doesn’t for­mal­ly change who has pow­er over vac­cine and drug ap­proval, but it re­in­forces a sig­nal giv­en through­out the pan­dem­ic: “That Sec­re­tary Azar wants to be very clear that he has fi­nal word on de­ci­sions com­ing out of the FDA,” Mic­ah Berman, a for­mer FDA ad­vi­sor and a pro­fes­sor of pub­lic health and law at Ohio State Uni­ver­si­ty, told End­points News.

Al­though the FDA has his­tor­i­cal­ly op­er­at­ed as a large­ly in­de­pen­dent agency, HHS legal­ly has fi­nal say on its de­ci­sions. HHS sec­re­taries have rarely ex­er­cised that au­thor­i­ty, but Azar did so last month, strip­ping the agency of its abil­i­ty to reg­u­late lab-de­vel­oped Covid-19 tests.

The tim­ing of the memo and its form could have sig­nif­i­cant rip­ple ef­fects on the agency and its em­ploy­ees, two for­mer FDA of­fi­cials told End­points.

For­mer as­so­ciate com­mis­sion­er Pe­ter Pitts de­fend­ed Azar’s ra­tio­nale, call­ing it an un­der­stand­able move for ac­count­able and stream­lined gov­ern­ment but one that was timed bad­ly, guar­an­teed to sow con­fu­sion and feed pre-ex­ist­ing con­cerns about the Trump ad­min­is­tra­tion med­dling in the agency.

“From a tim­ing per­spec­tive, it on­ly adds grist to the mill that the FDA is politi­cized, which is in­cor­rect fac­tu­al­ly and un­fair per­son­al­ly,” Pitts said.

‘A slap in the face to the peo­ple at the FDA’

In an in­ter­view, Pe­ter Lurie, who now runs the Cen­ter for Sci­ence in the Pub­lic In­ter­est, said the memo wouldn’t im­pact guide­lines or de­ci­sions — the main way the FDA has in­flu­ences on Covid-19 pol­i­cy — on­ly more mi­nor reg­u­la­tions. But these de­ci­sions al­ready get cleared through the FDA rungs, he said, even if a low­er lev­el of­fi­cial gives the sig­na­ture.

“Imag­ine putting out a big rule with­out telling the sec­re­tary? It’s just pre­pos­ter­ous,” Lurie told us. “I think this is a slap in the face to the peo­ple at the FDA. I think the ad­min­is­tra­tion’s dis­dain for pub­lic em­ploy­ees is ap­par­ent in this.”

Func­tion­al­ly, the memo changes long­stand­ing prac­tice at the agency, where low­er lev­el of­fi­cials can sign off on rule changes with­out the sig­na­tures of the FDA com­mis­sion­er or HHS sec­re­tary. HHS says the memo “min­i­mizes lit­i­ga­tion risk,” an ap­par­ent ref­er­ence to ar­gu­ments ad­vanced by con­ser­v­a­tive groups that po­ten­tial­ly thou­sands of FDA rules are il­le­gal be­cause, they claim, the Con­sti­tu­tion’s ap­point­ments clause on­ly al­lows of­fi­cers di­rect­ly ap­point­ed by the gov­ern­ment to sign reg­u­la­tions.

In the case of Moose Jooce, et al. v. FDA, et al., the va­p­ing com­pa­ny ar­gued that the FDA’s 2016 reg­u­la­to­ry frame­work for va­p­ing de­vices was un­con­sti­tu­tion­al be­cause it was signed by the FDA’s Leslie Kux as op­posed to the FDA com­mis­sion­er. Got­tlieb signed it in 2019, adding in a note that said the sig­na­ture did not mean it had pre­vi­ous­ly been il­le­gal.

A fed­er­al court, though, de­cid­ed against Moose Jooce ear­li­er this year and de­nied their mo­tion for ex­pe­dit­ed ap­peal. And the for­mer of­fi­cials said if HHS was con­cerned about it, they could have act­ed years ear­li­er, and they could have made the pol­i­cy that the FDA com­mis­sion­er, who is al­so di­rect­ly ap­point­ed by the pres­i­dent, signs off on all rules.

“As far as I know, none of that lit­i­ga­tion has been suc­cess­ful,” Berman said. “It’s not clear that it was a le­gal threat in the first place.”

So what will this mean lo­gis­ti­cal­ly in­side the FDA? It’s not clear yet. Pass­ing every rule through Azar could cause an ad­min­is­tra­tive headache, as for­mer FDA com­mis­sion­er Mark Mc­Clel­lan has warned. Lurie, though, not­ed that the rules aren’t signed on a dai­ly ba­sis, so it may not prove a sig­nif­i­cant bur­den.

There was al­so con­cern that the memo would val­i­date Moose Jooce’s ar­gu­ment and po­ten­tial­ly in­val­i­date thou­sands of FDA rules, though Berman said that would re­quire in­di­vid­ual chal­lenges to each rule. Moose Jooce, mean­while, is car­ry­ing on with their ap­peal. They gave oral ar­gu­ments at the DC Cir­cuit Court of Ap­peals on Wednes­day.

Jonathan Wood, who is ar­gu­ing the case for the Pa­cif­ic Le­gal Foun­da­tion, said he wel­comed the memo. But he too was won­der­ing about the tim­ing and said he had his own the­o­ry.

“This has been an is­sue HHS has known about for years, at the very least since we filed the com­plaint sev­er­al years ago and through­out the process of lit­i­gat­ing this case, they’ve said this is to­tal­ly fine, we’re not go­ing to stop it, con­tin­ue to have em­ploy­ees is­sue rules,” he told End­points. “Maybe it’s a co­in­ci­dence that they sud­den­ly changed the prac­tice one week be­fore the DC Cir­cuit heard oral ar­gu­ments?”

BY­OD Best Prac­tices: How Mo­bile De­vice Strat­e­gy Leads to More Pa­tient-Cen­tric Clin­i­cal Tri­als

Some of the most time- and cost-consuming components of clinical research center on gathering, analyzing, and reporting data. To improve efficiency, many clinical trial sponsors have shifted to electronic clinical outcome assessments (eCOA), including electronic patient-reported outcome (ePRO) tools.

In most cases, patients enter data using apps installed on provisioned devices. At a time when 81% of Americans own a smartphone, why not use the device they rely on every day?

Image: Shutterstock

Eli Lil­ly asks FDA to re­voke EUA for Covid-19 treat­ment

Eli Lilly on Friday requested that the FDA revoke the emergency authorization for its Covid-19 drug bamlanivimab, which is no longer as effective as a combo therapy because of a rise in coronavirus variants across the US.

“With the growing prevalence of variants in the U.S. that bamlanivimab alone may not fully neutralize, and with sufficient supply of etesevimab, we believe now is the right time to complete our planned transition and focus on the administration of these two neutralizing antibodies together,” Daniel Skovronsky, Lilly’s CSO, said in a statement.

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Ex­clu­sive in­ter­view: Pe­ter Marks on why full Covid-19 vac­cine ap­provals could be just months away

Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, took time out of his busy schedule last Friday to discuss with Endpoints News all things related to his work regulating vaccines and the pandemic.

Marks, who quietly coined the name “Operation Warp Speed” before deciding to stick with his work regulating vaccines at the FDA rather than join the Trump-era program, has been the face of vaccine regulation for the FDA throughout the pandemic, and is usually spotted in Zoom meetings seated in front of his wife’s paintings.

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J&J faces CDC ad­vi­so­ry com­mit­tee again next week to weigh Covid-19 vac­cine risks

The CDC’s Advisory Committee on Immunization Practices punted earlier this week on deciding whether or not to recommend lifting a pause on the administration of J&J’s Covid-19 vaccine, but the committee will meet again in an emergency session next Friday to discuss the safety issues further.

The timing of the meeting likely means that the J&J vaccine will not return to the US market before the end of next week as the FDA looks to work hand-in-hand with the CDC to ensure the benefits of the vaccine still outweigh the risks for all age groups.

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Mer­ck scraps their $425M Covid-19 drug in lat­est pan­dem­ic set­back

Seven months after paying $425 million cash to acquire it, Merck is scrapping a Covid-19 drug they hoped could provide one of the only treatments for severe hospitalized patients.

Merck’s decision comes after they faced significant and unexpected regulatory delays in getting the drug, known as MK-7110 or CD24Fc, across the finish line. The Big Pharma licensed the drug under the belief that it had already shown sufficient benefit in severe patients and they could help scale it up far faster than OncoImmune, its former owner, could. But in February, the company reported that the FDA insisted Merck run a new trial before seeking authorization.

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Joe Biden (Carolyn Kaster, AP Images)

Covid-19 roundup: Biden in­vests $1.7B to ad­dress Covid vari­ants; EU puts faith in Pfiz­er with new vac­cine deals

The Biden administration said Friday that it’ll pump $1.7 billion into various programs to address Covid-19 variants as the original strain of Covid-19 makes up only about half of all US cases today.

Most of those new funds, $1 billion in total, will go to expand genomic sequencing so the CDC, states and other jurisdictions can improve their capacity to identify Covid mutations and monitor the circulation of variants. Back in February, US labs were only sequencing about 8,000 Covid-19 strains per week, although the rate of sequencing has increased substantially since then, the administration said.

Osman Kibar (Samumed, now Biosplice)

Os­man Kibar lays down his hand at Sa­mumed, step­ping away from CEO role as his once-her­ald­ed an­ti-ag­ing biotech re­brands

Samumed made quite the entrance back in 2016, when it launched with some anti-aging programs and a whopping $12 billion valuation. That level of fanfare was nowhere to be found on Thursday, when the company added another $120 million to its coffers and quietly changed its name to Biosplice Therapeutics.

Why the sudden rebrand?

“We did that for obvious reasons,” CFO and CBO Erich Horsley told Endpoints News. “The name Biosplice echoes our science much more than Samumed does.”

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Near­ly a year af­ter Au­den­tes' gene ther­a­py deaths, the tri­al con­tin­ues. What hap­pened re­mains a mys­tery

Natalie Holles was five months into her tenure as Audentes CEO and working to smooth out a $3 billion merger when the world crashed in.

Holles and her team received word on the morning of May 5 that, hours before, a patient died in a trial for their lead gene therapy. They went into triage mode, alerting the FDA, calling trial investigators to begin to understand what happened, and, the next day, writing a letter to alert the patient community so they would be the first to know. “We wanted to be as forthright and transparent as possible,” Holles told me late last month.

The brief letter noted two other patients also suffered severe reactions after receiving a high dose of the therapy and were undergoing treatment. One died a month and a half later, at which point news of the deaths became public, jolting an emergent gene therapy field and raising questions about the safety of the high doses Audentes and others were now using. The third patient died in August.

“It was deeply saddening,” Holles said. “But I was — we were — resolute and determined to understand what happened and learn from it and get back on track.”

Eleven months have now passed since the first death and the therapy, a potential cure for a rare and fatal muscle-wasting disease called X-linked myotubular myopathy, is back on track, the FDA having cleared the company to resume dosing at a lower level. Audentes itself is no more; last month, Japanese pharma giant Astellas announced it had completed working out the kinks of the $3 billion merger and had restructured and rebranded the subsidiary as Astellas Gene Therapies. Holles, having successfully steered both efforts, departed.

Still, questions about precisely what led to the deaths of the 3 boys still linger. Trial investigators released key details about the case last August and December, pointing to a biological landmine that Audentes could not have seen coming — a moment of profound medical misfortune. In an emerging field that’s promised cures for devastating diseases but also seen its share of safety setbacks, the cases provided a cautionary tale.

Audentes “contributed in a positive way by giving a painful but important example for others to look at and learn from,” Terry Flotte, dean of the UMass School of Medicine and editor of the journal Human Gene Therapy, told me. “I can’t see anything they did wrong.”

Yet some researchers say they’re still waiting on Astellas to release more data. The company has yet to publish a full paper detailing what happened, nor have they indicated that they will. In the meantime, it remains unclear what triggered the events and how to prevent them in the future.

“Since Audentes was the first one and we don’t have additional information, we’re kind of in a holding pattern, flying around, waiting to figure out how to land our vehicles,” said Jude Samulski, professor of pharmacology at UNC’s Gene Therapy Center and CSO of the gene therapy biotech AskBio, now a subsidiary of Bayer.

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Spon­sors should flag de­cen­tral­ized as­pects of can­cer tri­als to prep for the post-Covid era, FDA says

As more and more clinical trials during the pandemic have harnessed the power of remote assessments and modifications, the FDA Oncology Center of Excellence and the Office of Oncologic Diseases are now requesting that applicants voluntarily add flags to datasets to discriminate between remote assessments and trial site assessments.

The push from the FDA to flag these differences is part of an effort to ameliorate the fact that there is currently no standard way to identify Covid-related modifications in clinical trial datasets submitted to the FDA. And many of these remote modifications were deployed in the middle of large ongoing cancer trials as a way to minimize Covid risks, the agency said.