Janet Woodcock and Francis Collins

Janet Wood­cock and Fran­cis Collins dish on lessons learned from the pan­dem­ic

With al­most 550,000 Covid-19 deaths in the US, it might seem hard to fath­om any sil­ver lin­ings from such a tragedy. But NIH di­rec­tor Fran­cis Collins and FDA act­ing com­mis­sion­er Janet Wood­cock did their best on Wednes­day to ex­plain what they’ve seen and learned and what the coun­try needs to do to pre­pare for the next pan­dem­ic.

For Wood­cock, who led the ther­a­peu­tics side of Op­er­a­tion Warp Speed be­fore re­turn­ing to lead the FDA, Covid-19 clin­i­cal tri­al in­ef­fi­cien­cies and a dearth of com­mu­ni­ty-based re­search in­fra­struc­ture sit atop her list.

While point­ing to her pub­li­ca­tion last month in Na­ture Re­views Drug Dis­cov­ery, she ex­plained how just 5% of the al­most 3,000 Covid-19 ther­a­peu­tic tri­als were ac­tu­al­ly ran­dom­ized and ad­e­quate­ly pow­ered to re­veal ac­tion­able da­ta.

“There was a tremen­dous amount of du­pli­ca­tion, and a lot of small tri­als that yield­ed tan­ta­liz­ing in­for­ma­tion that sent peo­ple off to use treat­ments that were not use­ful and po­ten­tial­ly harm­ful,” Wood­cock said at the Milken In­sti­tute event. “In a glob­al emer­gency we need to have more cen­tral co­or­di­na­tion be­cause we should re­al­ly ran­dom­ize the first pa­tient.”

On the lack of re­search in­fra­struc­ture, Wood­cock ex­plained how com­mu­ni­ties with­out aca­d­e­m­ic med­ical cen­ters or ad­e­quate­ly trained per­son­nel were stuck with­out any op­tions for en­rolling peo­ple in tri­als. “You can’t just build up in­fra­struc­ture ca­pac­i­ty in the mid­dle of a pan­dem­ic,” she said. “We had tens of thou­sands of peo­ple dy­ing from Covid and we couldn’t get enough pa­tients en­rolled in some tri­als.”

Collins, mean­while, point­ed to three lessons learned. The first is to en­sure NIH and the phar­ma in­dus­try main­tain its pub­lic-pri­vate part­ner­ship, known as AC­TIV, which bet­ter co­or­di­nat­ed and stream­lined bio­med­ical re­search re­sources for test­ing new and re­pur­posed com­pounds to treat Covid-19.

“If we can do it in two weeks, as we did with AC­TIV, we can prob­a­bly do it again and make these kinds of part­ner­ships,” Collins said.

Sec­ond­ly, he point­ed to the dis­con­nect in the clin­i­cal tri­al net­works in the US, not­ing Wood­cock’s com­ments. While he said the du­plica­tive and po­ten­tial­ly un­help­ful tri­als weren’t re­ceiv­ing funds from NIH, they may have been us­ing NIH-fund­ed in­fra­struc­ture.

“We can­not let this clin­i­cal tri­al ecosys­tem fall back in­to this scat­ter­shot ap­proach or we’ll be sor­ry. We need a much more rig­or­ous ap­proach. If we need­ed the ev­i­dence, we now have it,” Collins said.

And third­ly, he point­ed to the need for con­tin­u­ing NIH’s ven­ture cap­i­tal-like strat­e­gy used in its RADx com­pe­ti­tion to speed new Covid-19 tests to mar­ket.

“There’s a lot of tech­nolo­gies out there,” he added, not­ing the Shark Tank ap­proach may be bet­ter suit­ed for many of the ones in de­vel­op­ment, as op­posed to the NIH grant process, which can take more time.

Last­ly, both Wood­cock and Collins point­ed to the need to in­crease the di­ver­si­ty of clin­i­cal tri­als, which Collins not­ed was a heavy lift for some of the Covid-19 vac­cine de­vel­op­ers.

“The way in which bio­med­ical re­search works is con­t­a­m­i­nat­ed by struc­tur­al racism,” Collins said.

Wood­cock echoed that sen­ti­ment, ex­plain­ing how of­ten tri­als are run in dif­fer­ent coun­tries but they don’t nec­es­sar­i­ly re­flect the di­ver­si­ty of the US pop­u­la­tion.

For a look at all End­points News coro­n­avirus sto­ries, check out our spe­cial news chan­nel.

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

What lured Hal Bar­ron away?; Top FDA minds on ac­cel­er­at­ed ap­proval re­forms; ‘Dead wrong’ Aduhelm ad blitz; 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.

Nothing can really compete with Hal Barron’s departure from GlaxoSmithKline as the news of the week, but we do have plenty of original reporting and analysis from the Endpoints team in this edition. Enjoy and have a nice weekend.

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Covid-19 roundup: HHS may strug­gle to ab­sorb Op­er­a­tion Warp Speed; Eu­rope has no plans for a fourth vac­cine dose

Operation Warp Speed, perhaps the greatest achievement of the former Trump administration, promptly delivered Covid-19 vaccine supplies nationwide when they became available, thanks to collaborations between HHS and the Department of Defense, while helping to fund and aid the manufacture of billions of doses.

But since the Biden administration took over a year ago, acting FDA commissioner Janet Woodcock transitioned out of her role as the therapeutics lead in Warp Speed, which has been converted into a new operation without the fancy name (now known as the “HHS-DOD COVID-19 Countermeasures Acceleration Group”), and as of the start of 2022, the Department of Defense is no longer helping HHS on the program.

Mer­ck wins le­gal bat­tle over in­sur­ance cov­er­age af­ter ran­somware at­tack

Merck has emerged victorious from a years-long legal battle with insurers over the coverage of more than a billion dollars in losses from the malware NotPetya, with a New Jersey Superior Court judge concluding that the responsibility is on insurers to clarify their policies around cyber attacks.

The pharma giant was one of several victims of a global cyber attack back in 2017 that also hit Danish shipping company Maersk, American food company Mondelēz, French construction giant Saint-Gobain and even the systems monitoring the Chernobyl nuclear power stations, Bloomberg reported back in 2019.

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Crit­ics push back on Alzheimer’s As­so­ci­a­tion ad blitz to get Medicare to change its Aduhelm rul­ing: 'Dead wrong'

The latest Alzheimer’s Association advertising campaign encourages people to fight.

Not against the disease or for more research or treatments, but against the Centers for Medicare and Medicaid Services. More specifically, CMS’ recent reimbursement decision to only pay for Biogen and Eisai’s controversial Alzheimer’s drug Aduhelm for patients in clinical trials.

With CMS’ preliminary decision now in a 30-day comment period, patient advocates’ goal is to convince CMS to reverse its decision with a marketing blitz and public pressure.

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Dan O'Day, Gilead CEO (Jim Watson/AFP via Getty Images)

Fail­ing to con­firm clin­i­cal ben­e­fit, Gilead pulls 2 ac­cel­er­at­ed ap­proval in­di­ca­tions for can­cer drug

Gilead recently decided to pull two indications for its cancer drug Zydelig — in relapsed follicular B-cell non-Hodgkin lymphoma (FL) and relapsed small lymphocytic leukemia (SLL) — after failing to complete the confirmatory trials required as part of the accelerated approvals from 2014.

“As the treatment landscape for FL and SLL has evolved, enrollment into the confirmatory study has been an ongoing challenge,” Gilead said in a statement, noting it formally notified the FDA of its decision to voluntarily withdraw these indications.

Richard Pazdur (via AACR)

Time lim­its on ac­cel­er­at­ed ap­provals? FDA's on­col­o­gy chief Rick Paz­dur eyes po­ten­tial re­forms via in­ter­na­tion­al ap­proach­es

The spotlight on the accelerated approval pathway continues to shine bright, with the FDA’s top oncology official writing in an opinion that the pathway may be strengthened with bits and pieces of what other regulators in Europe and elsewhere have done with their expedited approval pathways, such as adding expiration dates for these faster approvals to ensure they confirm clinical benefit in a timely manner.

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Hal Barron, Endpoints UKBIO20 (Jeff Rumans)

'Al­tos was re­al­ly a once-in-a-life­time op­por­tu­ni­ty': Hal Bar­ron re­flects on his big move

By all accounts, Hal Barron had one of the best jobs in Big Pharma R&D. He made more than $11 million in 2020, once again reaping more than his boss, Emma Walmsley, who always championed him at every opportunity. And he oversaw a global R&D effort that struck a variety of big-dollar deals for oncology, neurodegeneration and more.

Sure, the critics never let up about what they saw as a rather uninspiring late-stage pipeline, where the rubber hits the road in the Big Pharma world’s hunt for the next big near-term blockbuster, but the in-house reviews were stellar. And Barron was firmly focused on bringing up the success rate in clinical trials, holding out for the big rewards of moving the dial from an average 10% success rate to 20%.

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Executive Director of the EMA Emer Cooke (AP Photo/Geert Vanden Wijngaert)

Eu­ro­pean Par­lia­ment signs off on strength­en­ing drug reg­u­la­tor's abil­i­ty to tack­le short­ages

The European Parliament on Thursday endorsed a plan to increase the powers of the European Medicines Agency, which will be better equipped to monitor and mitigate shortages of drugs and medical devices.

By a vote of 655 to 31, parliament signed off on a provisional agreement reached with the European Council from last October, in which the EMA will create two shortage steering groups (one for drugs, the other for devices), a new European Shortages Monitoring Platform to facilitate data collection and increase transparency, and on funding for the work of the steering groups, task force, working parties and expert panels that are to be established.

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