Peter Marks (Greg Nash/Pool via AP Images)

FDA cen­ter di­rec­tors on lessons from the EUA path­way: Flex­i­bil­i­ty serves us well

The flex­i­bil­i­ty of emer­gency use au­tho­riza­tions, and al­low­ing the FDA to ac­cept more un­cer­tain­ty dur­ing the pan­dem­ic so far, has ul­ti­mate­ly aid­ed its re­sponse to Covid-19, cen­ter di­rec­tors said Tues­day at a work­shop at the Na­tion­al Acad­e­mies of Sci­ences, En­gi­neer­ing and Med­i­cine.

Pa­trizia Cavaz­zoni

Pa­trizia Cavaz­zoni, di­rec­tor of the FDA’s Cen­ter for Drug Eval­u­a­tion and Re­search, point­ed to the agili­ty of the EUAs, and the abil­i­ty to quick­ly re­voke any EUAs, as well as the trans­paren­cy around those de­ci­sions as to what led to the evo­lu­tion of the types of ther­a­peu­tics that have been au­tho­rized (see chart be­low).

“Agili­ty is very im­por­tant, and the EUA al­lows us that,” she said, stress­ing the abil­i­ty to re­voke EUAs very quick­ly and say­ing FDA wish­es it had that abil­i­ty, when the da­ta war­rant­ed, out­side of the pan­dem­ic.

“The big take­away for me, based on the past sev­er­al months, is the im­por­tance of col­lab­o­ra­tion across the US gov­ern­ment agen­cies and with in­ter­na­tion­al coun­ter­parts and the re­search com­mu­ni­ty,” Cavaz­zoni said. “The oth­er im­por­tant take­away is hav­ing a reg­u­la­to­ry frame­work that al­lows us to be ag­ile and flex­i­ble.”

It’s im­por­tant for the pub­lic to un­der­stand the ev­i­dence and da­ta gen­er­a­tion con­tin­ues even af­ter an EUA, Cavaz­zoni said, of­fer­ing the ex­am­ple of hy­drox­y­chloro­quine, which had its EUA re­voked:

What has been lost in this dis­cus­sion is that au­tho­riza­tion was in­cred­i­bly nar­row and the fact sheet specif­i­cal­ly said it should be lim­it­ed to pa­tients who could not be in clin­i­cal tri­als. Al­most im­me­di­ate­ly af­ter these tri­als read out, the EUA was re­voked. De­spite that, there was so much noise around this and it’s part of our lessons learned on com­mu­ni­cat­ing facts.

With the au­tho­rized mon­o­clon­al an­ti­bod­ies for Covid-19, Cavaz­zoni not­ed that it was clear these could save lives but “what we saw was very slow up­take last fall and in­to the spring un­til this sum­mer where fi­nal­ly the mes­sage went through and now we have lim­it­ed sup­plies. We need to work to­geth­er more ef­fec­tive­ly to break through the noise.”

Josh Sharf­stein

Josh Sharf­stein, a Johns Hop­kins pro­fes­sor who was once con­sid­ered for the top FDA com­mis­sion­er po­si­tion, al­so ques­tioned the cen­ter di­rec­tors ear­li­er on Tues­day on how in­dus­try of­ten leads the con­ver­sa­tion around the da­ta on new Covid-re­lat­ed ther­a­peu­tics and vac­cines.

Cavaz­zoni said her cen­ter is “con­strained by laws and reg­u­la­tions on what we com­mu­ni­cate” and from its per­spec­tive, “we would wel­come broad­er au­thor­i­ties when it comes to com­mu­ni­ca­tion about the pro­grams, not on­ly on is­suance of EUAs and ed­u­ca­tion, as well as EUAs that end up be­ing de­clined. I think this is an area prime for fur­ther think­ing.”

Pe­ter Marks, di­rec­tor of the FDA’s Cen­ter for Bi­o­log­ics Eval­u­a­tion and Re­search, added that he’s hes­i­tant to call for any ma­jor changes to the EUA path­way. “It’s not that usu­al that I think of a par­tic­u­lar statu­to­ry au­thor­i­ty as in­cred­i­bly well craft­ed but our emer­gency use au­tho­riza­tion is craft­ed quite well to deal with a range of things that can come our way and it’s up to us to en­sure it’s used prop­er­ly, not to mess around with the statute.”

“If we’re think­ing about any­thing in this area, it’s mi­nor re­dec­o­ra­tion, not ren­o­va­tion,” he said. Ear­li­er in the pan­el dis­cus­sion Marks men­tioned the idea of po­ten­tial­ly com­bin­ing the ef­forts of the FDA’s vac­cine ad­comm VRB­PAC and the CDC’s sep­a­rate ad­comm ACIP. “The process ul­ti­mate­ly works in that sci­ence cor­rect­ed some of the er­rors that were made. Yes, it might have been nice if they weren’t made in re­al time but I think the trans­paren­cy helps.”

“The thing I won­der in the vac­cine realm if we could have bet­ter co­or­di­nat­ed things to es­sen­tial­ly col­lapse the VRB­PAC process with the Ad­vi­so­ry Com­mit­tee on Im­mu­niza­tion Prac­tices process,” he said. “We need to look care­ful­ly at this, ACIP was de­vel­oped for rou­tine vac­cines and for that mat­ter, for coun­ter­mea­sures not for the mid­dle of an emer­gency.”

And in a coun­try where there’s al­ways been vac­cine hes­i­tan­cy, “that’s not the best time to have any air space be­tween two ad­vi­so­ry com­mit­tees,” Marks said. “I think we as a fed­er­al gov­ern­ment need to do a re­al­ly good job to make sure our mes­sag­ing is har­mo­nized.”

Jeff Shuren

The com­ments come as the FDA’s and CDC’s ad­comms and lead­ers re­cent­ly clashed over what groups of peo­ple should first re­ceive boost­er shots fol­low­ing the re­cent EUA. Two of the top vac­cine ex­perts work­ing un­der Marks re­cent­ly an­nounced their re­tire­ments were due at least in part to con­cerns with the way the boost­er EUA process played out.

On the med­ical de­vice side, CDRH head Jeff Shuren not­ed that the EUA au­thor­i­ties have been in­cred­i­bly help­ful giv­en the vol­ume of prod­ucts com­ing in through the door. “With­out a na­tion­al test­ing strat­e­gy, we’re do­ing all com­ers, rather than hav­ing a tar­get­ed ap­proach,” he said. He al­so not­ed the EUA path­way was in­valu­able in speed­ing new tests and di­ag­nos­tics, adding, “I re­al­ly wish we had that flex­i­bil­i­ty in peace time.”

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

Christian Itin, Autolus CEO (UKBIO19)

Au­to­lus tips its hand, bags $220M as CAR-T show­down with Gilead looms

The first batch of pivotal data on Autolus Therapeutics’ CAR-T is in, and execs are ready to plot a path to market.

With an overall remission rate of 70% at the interim analysis featuring 50 patients, the results set the stage for a BLA filing by the end of 2023, said CEO Christian Itin.

Perhaps more importantly — given that Autolus’ drug, obe-cel, is going after an indication that Gilead’s Tecartus is already approved for — the biotech highlighted “encouraging safety data” in the trial, with a low percentage of patients experiencing severe immune responses.

Ahead of ad­comm, FDA rais­es un­cer­tain­ties on ben­e­fit-risk pro­file of Cy­to­ki­net­ic­s' po­ten­tial heart drug

The FDA’s Cardiovascular and Renal Drugs Advisory Committee will meet next Tuesday to discuss whether Cytokinetics’ potential heart drug can safely reduce the risk of cardiovascular death and heart failure in patients with symptomatic chronic heart failure with reduced ejection fraction.

The drug, known as omecamtiv mecarbil and in development for more than 15 years, has seen mixed results, with a first Phase III readout from November 2020 hitting the primary endpoint of reducing the odds of hospitalization or other urgent care for heart failure by 8%. But it also missed a key secondary endpoint analysts had pegged as key to breaking into the market.

Dipal Doshi, Entrada Therapeutics CEO

Ver­tex just found the next big ‘trans­for­ma­tive’ thing for the pipeline — at a biotech just down the street

Back in the summer of 2019, when I was covering Vertex’s executive chairman Jeff Leiden’s plans for the pipeline, I picked up on a distinct focus on myotonic dystrophy Type I, or DM1 — one of what Leiden called “two diseases (with DMD) we’re interested in and we continue to look for those assets.”

Today, Leiden’s successor at the helm of Vertex, CEO Reshma Kewalramani, is plunking down $250 million in cash to go the extra mile on DM1. The lion’s share of that is for the upfront, with a small reserve for equity in a deal that lines Vertex up with a neighbor in Seaport that has been rather quietly going at both of Vertex’s early disease targets with preclinical assets.

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David Light, Valisure CEO

Val­isure in the hot seat: New Form 483 over a 2021 in­spec­tion as CEO fires back

The notorious drug testing company Valisure, which has made a name for itself by forcing FDA’s hand with some of its safety-related uncoverings, received a letter this week after the FDA uncovered violations at its Connecticut-based testing lab in 2021.

The letter, which was sent on Dec. 5, stated that the FDA is “concerned” that Valisure was not aware of  drug supply chain security requirements.

WIB22: Am­ber Salz­man had few op­tions when her son was di­ag­nosed with a rare ge­net­ic dis­ease. So she cre­at­ed a bet­ter one

This profile is part of Endpoints News’ 2022 special report about Women in Biopharma R&D. You can read the full report here.

Amber Salzman’s life changed on a cold, damp day in Paris over tiny plastic cups of lukewarm tea.

She was meeting with Patrick Aubourg, a French neurologist studying adrenoleukodystrophy, or ALD, a rare genetic condition that causes rapid neurological decline in young boys. It’s a sinister disease that often leads to disability or death within just a few years. Salzman’s nephew was diagnosed at just 6 or 7 years old, and died at the age of 12.

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FDA re­view­ers head back to White Oak in 2023, with lead­er­ship look­ing to ap­pease a new Con­gress

Republicans have taken a stand against the pandemic era habit of lax work-from-home schedules. Now that they’ve wrestled control of the House majority, the FDA’s leadership is playing ball, sending many of the agency’s more than 18,000 employees back to their desks early next year.

Whether this exodus back to White Oak in Silver Spring, MD (many staff will still be allowed to work from home for multiple days per week) will mean more defections to industry and elsewhere remains to be seen.

Bags of shred­ded docs: In­di­an drug­mak­er Lupin hand­ed a Form 483 by FDA in­spec­tors

The generics manufacturer Lupin has been given another Form 483 from the FDA this year.

US regulators inspected Lupin’s pharmaceutical manufacturing site in the town of Mandideep, India from Nov. 14 through Nov. 23, with the 14-page report marking 16 observations.

The inspection report stated that the site did not have the appropriate controls over its computer systems to ensure that changes in “master production” or records are only done by authorized personnel, along with written procedures not being established to conduct annual reviews of records associated with drug batches.

Bro­ken promis­es? FDA needs more pow­er to re­move drugs from mar­ket­place, JA­MA analy­sis finds

The FDA is struggling to remove drugs from the marketplace that don’t show effectiveness in late stage trials, new JAMA analyses found, thanks to the persistent tension between speed and confidence in early clinical data.

Congress, regulated industry and patients have urged the FDA to shorten the amount of time that the market has to wait for drugs to become available that may help severe and prevalent diseases – and the FDA has listened, offering up a quick accelerated approval pathway that’s frequently used by new cancer drugs.