Four ex­perts from the FDA’s On­col­o­gy Cen­ter of Ex­cel­lence took to the New Eng­land Jour­nal of Med­i­cine yes­ter­day to make the case for not on­ly im­prov­ing the agency’s abil­i­ty to ex­pe­di­tious­ly pull dan­gling ac­cel­er­at­ed ap­provals when, on the rare oc­ca­sion, con­fir­ma­to­ry tri­als fail, but al­so bet­ter build­ing “qual­i­ty and ef­fi­cien­cy in­to the AA on-ramp.”

The time­ly per­spec­tive ar­rives as Con­gress has ex­act­ly one week left to draft, re­lease and sign off on the reau­tho­rized user fee deals be­fore lay­off no­tices will be sent to drug re­view­ers. That pack­age, which is like­ly to hitch a ride with the con­tin­u­ing res­o­lu­tion, may or may not in­clude sev­er­al pol­i­cy rid­ers (op­posed by Re­pub­li­cans), in­clud­ing one that would al­low the FDA to re­quire con­fir­ma­to­ry tri­als to be un­der­way be­fore an AA is grant­ed, and would im­prove the process by which FDA can with­draw AAs.

The FDA au­thors make clear the need for such an AA rid­er as for on­col­o­gy in­di­ca­tions that have been grant­ed AAs, the me­di­an time to be­gin­ning the with­draw­al process “was longer if the con­fir­ma­to­ry tri­al was ini­ti­at­ed af­ter the ap­proval (see fig­ure). This dif­fer­ence was most strik­ing among with­drawn in­di­ca­tions, with a me­di­an time to with­draw­al of 3.8 years if the con­fir­ma­to­ry tri­al was on­go­ing at the time of AA, as com­pared with 7.3 years if such a tri­al had not been ini­ti­at­ed. De­layed with­drawals in this lat­ter sce­nario rep­re­sent the great­est risk to pa­tients.”

OCE’s Lo­la Fashoyin-Aje, Gau­tam Mehta, Ju­lia Beaver, and Richard Paz­dur al­so of­fer sev­er­al up­front op­tions for those pur­su­ing AAs.

For in­stance, spon­sors could pur­sue a sin­gle ran­dom­ized tri­al, po­ten­tial­ly in an ear­li­er treat­ment set­ting, that could both sup­port AA and ver­i­fy clin­i­cal ben­e­fit, they say, with the ac­cel­er­at­ed ap­proval com­ing on the ba­sis of a planned in­ter­im analy­sis of ORR, and a con­ver­sion to full ap­proval grant­ed on the ba­sis of clin­i­cal ben­e­fit (OS im­prove­ment) at the tri­al’s con­clu­sion.

“This ap­proach would pro­vide a more thor­ough safe­ty as­sess­ment and ear­li­er de­fin­i­tive ev­i­dence of the ben­e­fit–risk bal­ance. It would al­so re­duce the risk of pre­ma­ture­ly halt­ing de­vel­op­ment of a drug with a lim­it­ed over­all re­sponse rate that might nev­er­the­less im­prove over­all sur­vival,” they wrote.

An­oth­er po­ten­tial strat­e­gy for spon­sors would be to agree in ad­vance on the cri­te­ria for at­tain­ing AA, and the cri­te­ria for with­draw­ing the in­di­ca­tion. Spon­sors could then run two con­cur­rent stud­ies: a sin­gle-group AA study ex­am­in­ing the ORR in pa­tients with­out oth­er avail­able ther­a­pies, and a ran­dom­ized tri­al fo­cused on clin­i­cal ben­e­fit in pa­tients who have re­ceived few­er treat­ments.

“If these stud­ies en­rolled pa­tients around the same time, an in­ter­im analy­sis of safe­ty and over­all re­sponse rate in the con­fir­ma­to­ry tri­al could pro­vide sup­port­ive ev­i­dence and greater con­fi­dence for the AA based on the sin­gle-group study,” they ex­plain.

Mov­ing for­ward, OCE’s Fashoyin-Aje et. al. ex­plain how both the at-times de­layed with­draw­al process (the fo­cus on Con­gres­sion­al ef­forts) should not over­shad­ow the lead-up to an ap­proval.

“Pub­lic dis­cus­sion has fo­cused on im­prov­ing the AA off-ramp, sug­gest­ing spe­cif­ic time lim­its for com­plet­ing con­fir­ma­to­ry tri­als, pa­tient en­roll­ment mile­stones for eval­u­at­ing time­ly tri­al com­ple­tion, and al­ter­na­tive pro­ce­dures for with­draw­ing in­di­ca­tions. But equal­ly im­por­tant are pro­ce­dures to build qual­i­ty and ef­fi­cien­cy in­to the AA on-ramp, which should in­clude a prospec­tive com­pre­hen­sive strat­e­gy de­tail­ing plans for AA and the ver­i­fi­ca­tion of clin­i­cal ben­e­fit, with the aim of ex­pe­dit­ing ther­a­peu­tic ad­vances and short­en­ing this pe­ri­od of un­cer­tain­ty,” they con­clud­ed.

President Joe Biden made clear in his “finish the job” State of the Union address last night that one of those jobs to be finished is insulin prices.

Biden’s push again to tackle insulin prices, after Republicans rebuffed the idea last summer and just after Biden won Medicare drug price negotiations/caps via the Inflation Reduction Act, shows how heavily he’s leaning into this work.

FDA Commissioner Rob Califf joined the heads of the CDC and NIH in the hot seat today before a key House subcommittee, explaining that there needs to be a much faster, more coordinated way to oversee vaccine safety, and that foreign biopharma inspections, halted for years due to the pandemic, are slowly ramping up again.

Califf, who stressed to the House Energy and Commerce’s Subcommittee on Health that the CDC also needs better data, made clear that the FDA’s ability to monitor the safety of vaccines “would also benefit greatly by a coordinated federal public health data reporting authority.”

President Joe Biden will take to his second State of the Union this evening with plans for optimism, and a call for universal, $35 per month insulin, along with highlights of one of his biggest self-described successes so far — the defeat of pharma companies with the institution of Medicare negotiations for drug prices.

“President Biden took on Big Pharma — and won,” a White House fact sheet said ahead of the speech this evening.

Six weeks into his new role at the helm of Teva Pharmaceutical, Richard Francis said it’s time to “get back to growth,” starting with a good look at the company’s priorities.

The chief executive has kicked off a strategic review, he announced during Teva’s quarterly call, which will continue over the next several months and produce results sometime in the middle of 2023. That means some pipeline cuts may be in store, he told Endpoints News, while declining to offer much more detail.