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.”

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

So — that pig-to-hu­man trans­plant; Po­ten­tial di­a­betes cure reach­es pa­tient; Ac­cused MIT sci­en­tist lash­es back; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

We’re incredibly excited to welcome Beth Bulik, seasoned pharma marketing reporter, to the team. You can find much of her work in our new Marketing channel — and in her weekly newsletter, Endpoints PharmaRx, which will launch in early November. Add it to your subscriptions here.

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UP­DAT­ED: Agenus calls out FDA for play­ing fa­vorites with Mer­ck, pulls cer­vi­cal can­cer BLA at agen­cy's re­quest

While criticizing the FDA for what may be some favoritism towards Merck, Agenus on Friday officially pulled its accelerated BLA for its anti-PD-1 inhibitor balstilimab as a potential second-line treatment for cervical cancer because of the recent full approval for Merck’s Keytruda in the same indication.

The company said the BLA, which was due for an FDA decision by Dec. 16, was withdrawn “when the window for accelerated approval of balstilimab closed,” thanks to the conversion of Keytruda’s accelerated approval to a full approval four months prior to its PDUFA date.

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How to col­lect and sub­mit RWD to win ap­proval for a new drug in­di­ca­tion: FDA spells it out in a long-await­ed guid­ance

Real-world data are messy. There can be differences in the standards used to collect different types of data, differences in terminologies and curation strategies, and even in the way data are exchanged.

While acknowledging this somewhat controlled chaos, the FDA is now explaining how biopharma companies can submit study data derived from real-world data (RWD) sources in applicable regulatory submissions, including new drug indications.

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NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.

Pfiz­er pitch­es its Covid-19 vac­cine for younger chil­dren ahead of ad­comm next week

Pfizer will present its case to the FDA’s vaccine adcomm next week, seeking authorization for a lower-dose version of its Covid-19 vaccine for kids ages 5 through 12, which the Biden administration said will likely begin rolling out early next month.

Two primary doses of the 10 µg vaccine (the dose for those ages 12 and up is 30 μg) given 3 weeks apart in this group of children “have shown a favorable safety and tolerability profile, robust immune responses against all variants of concern including Delta, and vaccine efficacy of 90.7% against laboratory-confirmed symptomatic COVID-19,” the company said in briefing documents ahead of next Tuesday’s meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee.

David Livingston (Credit: Michael Sazel for CeMM)

Renowned Dana-Far­ber sci­en­tist, men­tor and bio­phar­ma ad­vi­sor David Liv­ingston has died

David Livingston, the Dana-Farber/Harvard Med scientist who helped shine a light on some of the key molecular drivers of breast and ovarian cancer, died unexpectedly last Sunday.

One of the senior leaders at Dana-Farber during his nearly half century of work there, Livingston was credited with shedding light on the genes that regulate cell growth, with insights into inherited BRCA1 and BRCA2 mutations that helped lay the scientific foundation for targeted therapies and earlier detection that have transformed the field.

Marty Duvall, Oncopeptides CEO

On­copep­tides stock craters as it pulls can­cer drug Pepax­to from the mar­ket

Shares of Oncopeptides crashed more than 70% in early Friday trading after the company said it’s pulling its multiple myeloma drug Pepaxto (melphalan flufenamide) from the US market after failing a confirmatory trial. The move will force the company to close its US and EU business units and enact significant layoffs.

The FDA had scheduled an adcomm meeting next Thursday to discuss Pepaxto, which first won accelerated approval in February and costs about $19,000 per course of treatment. The committee was to weigh in on whether the confirmatory trial demonstrated a worse overall survival in the treatment arm compared to the control arm.

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No­vo CEO Lars Fruer­gaard Jør­gensen on R&D risk, the deal strat­e­gy and tar­gets for gen­der di­ver­si­ty

 

I kicked off our European R&D summit last week with a conversation involving Novo Nordisk CEO Lars Fruergaard Jørgensen. Novo is aiming to launch a new era of obesity management with a new approval for semaglutide. And Jørgensen had a lot to say about what comes next in R&D, how they manage risk and gender diversity targets at the trendsetting European pharma giant.

John Carroll: I’m here with Lars Jørgensen, the CEO of Novo Nordisk. Lars, it’s been a really interesting year so far with Novo Nordisk, right? You’ve projected a new era of growing sales. You’ve been able to expand on the GLP-1 franchise that was already well established in diabetes now going into obesity. And I think a tremendous number of people are really interested in how that’s working out. You have forecast a growing amount of sales. We don’t know specifically how that might play out. I know a lot of the analysts have different ideas, how those numbers might play out, but that we are in fact embarking on a new era for Novo Nordisk in terms of what the company’s capable of doing and what it’s able to do and what it wants to do. And I wanted to start off by asking you about obesity in particular. Semaglutide has been approved in the United States for obesity. It’s an area of R&D that’s been very troubled for decades. There have been weight loss drugs that have come along. They’ve attracted a lot of attention, but they haven’t actually ever gained traction in the market. My first question is what’s different this time about obesity? What is different about this drug and why do you expect it to work now whereas previous drugs haven’t?

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