As he awaits a tight Sen­ate vote, Rob Califf, Pres­i­dent Joe Biden’s nom­i­nee to be the next FDA com­mis­sion­er, is sig­nal­ing where the agency may move on ac­cel­er­at­ed ap­provals if he takes over at FDA.

Build­ing off com­ments from his Sen­ate con­fir­ma­tion hear­ing, in which Califf said that he’s “a fan of ac­cel­er­at­ed ap­proval” but the US needs a bet­ter sys­tem to eval­u­ate these drugs once they’re on the mar­ket, the nom­i­nee raised ques­tions about how well the cur­rent struc­ture serves pa­tients.

There’s been “fail­ure to pro­duce con­fir­ma­to­ry ev­i­dence quick­ly and in a way that re­al­ly gives us the in­for­ma­tion we need as pa­tients and clin­i­cians to de­cide which treat­ments are most ef­fec­tive and in which or­der,” he said at the CER­SI Sum­mit last week.

Com­par­ing the ac­cel­er­at­ed ap­proval path­way to a re­lay race — po­ten­tial­ly pok­ing at the con­tro­ver­sial sit­u­a­tion where the FDA grant­ed an ac­cel­er­at­ed ap­proval to Bio­gen’s Alzheimer’s drug but CMS is re­quir­ing an ad­di­tion­al ran­dom­ized clin­i­cal tri­al — Califf ar­gued the “FDA runs the first lap, gets to the end, drops the ba­ton down on the ground, and some­one else like CMS has to fig­ure out where the ba­ton is, pick it up and start all over.”

“I think one of the most im­por­tant things I learned from my time [as FDA com­mis­sion­er un­der the Oba­ma ad­min­is­tra­tion] is the pow­er of fed­er­al agen­cies work­ing to­geth­er with com­mon pur­pose,” Califf said. “In a re­lay race, you have a num­ber of yards where the sec­ond run­ner is run­ning along­side the first, and we just don’t have that.”

He al­so lament­ed the fact that the US is “los­ing life ex­pectan­cy in the US and rel­a­tive­ly faster than the rest of the world. We’re in­no­vat­ing in the US in a way that’s help­ing the en­tire world, but there’s some­thing we’re not do­ing right in im­ple­ment­ing those in­no­va­tions. That’s the way I see it.”

Ju­lia Beaver

Ju­lia Beaver, chief of med­ical on­col­o­gy at the FDA’s On­col­o­gy Cen­ter of Ex­cel­lence, al­so spoke on the CER­SI pan­el with Califf, not­ing that over­all, OCE’s work in ac­cel­er­at­ed ap­provals has been “a suc­cess” by pro­vid­ing years of ear­ly ac­cess to “trans­for­ma­tive, life-pro­long­ing ther­a­pies.”

She not­ed that half of all ac­cel­er­at­ed ap­proval in­di­ca­tions have con­firmed ben­e­fit in a me­di­an of 3 years, and the re­main­der of those that have not yet con­firmed ben­e­fit have been those grant­ed AA in the last few years. Less than 10% of these in­di­ca­tions have been with­drawn ei­ther due to failed tri­als or be­cause the tri­als weren’t con­duct­ed, she said.

“The sit­u­a­tion and frame­work we’re in now is that al­though we can’t re­quire this, we are stress­ing the need for the con­fir­ma­to­ry tri­al to be well un­der­way, if not ful­ly en­rolled, at the time of the ac­cel­er­at­ed ap­proval ac­tion to avoid these de­lays and get the ev­i­dence,” Beaver said. “But in terms of our con­fi­dence in get­ting that con­fir­ma­to­ry ev­i­dence, that does now play in­to our over­all risk/ben­e­fit de­ci­sion. So if we have con­fi­dence or ear­ly agree­ment on ev­i­dence need­ed for con­fir­ma­to­ry tri­al, that’s the ide­al.”

Such ear­li­er agree­ments be­tween FDA and com­pa­nies seek­ing ac­cel­er­at­ed ap­provals, “po­ten­tial­ly even on con­fir­ma­to­ry met­rics,” Beaver not­ed, would al­low for greater con­fi­dence in the ap­proval path­way.

Hal Bar­ron, who re­cent­ly made the leap from CSO at Glax­o­SmithK­line to CEO of start­up Al­tos Labs, al­so not­ed on the pan­el that there a num­ber of sur­ro­gates where the ben­e­fit of an ac­cel­er­at­ed ap­proval is a “smart risk to take.” But “in terms of where it’s failed,” he stressed that there needs to be more rig­or in de­sign­ing the con­fir­ma­to­ry tri­als, “so you be­lieve” the re­sults when they’re pos­i­tive or neg­a­tive.

Hal Bar­ron

Some of these tri­als are tak­ing an “enor­mous­ly long time to con­vert” to full ap­proval, Bar­ron not­ed, and he said there’s been a lot of talk about us­ing RWE to sat­is­fy con­fir­ma­to­ry tri­al re­sults. “But I’m not as con­vinced that that will help as much as ran­dom­ized tri­als,” he said.

Califf, a long­time fan of us­ing RWE when ran­dom­ized, stressed, “Noth­ing about RWE ex­cludes ran­dom­iza­tion, which is one of the most pow­er­ful tools we have.” He point­ed to the UK-based Re­cov­ery tri­al, which quick­ly test­ed a num­ber of dif­fer­ent Covid-19 ther­a­peu­tics, and which “beat the socks off” the US tri­als.

“If the tri­als are most­ly en­rolled be­fore the [ac­cel­er­at­ed] ap­proval comes, you’re go­ing to get the an­swer,” Califf said.

Bar­ron, mean­while, not­ed the push to­ward do­ing more ob­ser­va­tion­al stud­ies and us­ing those to con­clude a drug works when com­pared to un­treat­ed pa­tients: “You can use all these so­phis­ti­cat­ed tech­niques, but I’m just not con­fi­dent. Giv­en that these drugs are go­ing to be used for a long, long time, we’ve got to get it right and not skimp­ing on the ran­dom­iza­tion, and un­der­stand­ing ef­fi­ca­cy and ef­fec­tive­ness is crit­i­cal.”

Bar­ron al­so stressed that for a small­er com­pa­ny, it can be a big risk to ini­ti­ate a con­fir­ma­to­ry tri­al be­fore an ap­proval is grant­ed or be­fore the sur­vey tri­als are un­blind­ed. He al­so called for more com­pa­nies to work in a pre-com­pet­i­tive way to de­fine the util­i­ty around the sur­ro­gates on which the ac­cel­er­at­ed ap­provals are based.

“What­ev­er leg­isla­tive frame­work is in­sert­ed, think hard about how every group has skin in the game. In­cen­tivize ap­provals to get to pa­tients faster but in­cen­tivize to quick­ly fig­ure out if you made a smart de­ci­sion that was wrong or a smart de­ci­sion that was right,” he added when asked how Con­gress could im­prove the ac­cel­er­at­ed path­way.

HHS on Thursday finalized its decision to withdraw a rule, proposed just before former President Donald Trump left office, that would’ve caused thousands of HHS and FDA regulations to automatically expire if they weren’t reviewed within two years, and every 10 years thereafter.

The decision follows the filing of a lawsuit last March, in which several nonprofits alleged that the outgoing administration planted “a ticking timebomb” for HHS, essentially forcing it to devote an enormous amount of resources to the unprecedented and infeasible task of reviewing thousands of regulations regularly.

At the end of January, the European Medicines Agency officially launched its new clinical trials info system (CTIS), although the migration to the new platform has only really just begun, and sponsors have until the end of January 2023 before all initial trial applications must be submitted through CTIS.

Overall, 56 clinical trial applications have been submitted in CTIS during the first 3 months since the launch of the system on Jan. 31, according to new data posted by the EMA. By comparison, about 4,000 new trials are authorized each year across Europe.

As concerns related to uptake and distribution continue to linger, Switzerland is among the first countries that plans to destroy hundreds of thousands of expired and unused Covid-19 vaccine doses.

The European country said it plans to destroy more than 600,000 doses of Moderna’s Spikevax Covid-19 vaccine as the doses have reached their expiration date.

However, Moderna CEO Stéphane Bancel told the World Economic Forum in Davos, Switzerland that he’s in the process of throwing 30 million doses in the garbage, exclaiming, “We have a big demand problem.”

As Neulasta sales slip, Amgen has yet another biosimilar to look out for: Amneal Pharmaceuticals and Kashiv Biosciences’ Flynetra.

Flynetra became the fifth approved biosimilar to Neulasta on Friday, snagging a win in neutropenia, a condition common among chemotherapy patients where neutrophils, a type of white blood cell that fights infection, are too low.

As of last summer, the list price of Neulasta was more than $6,400 per dose. It’s designed to be taken in a single dose per chemotherapy cycle. Amneal declined to reveal how much it intends to charge for Flynetra in an email to Endpoints News.