The next gen­er­a­tion of Op­er­a­tion Warp Speed is com­ing soon, and this time it’s go­ing to take aim at rare dis­eases, Pe­ter Marks, the di­rec­tor of the FDA’s Cen­ter for Bi­o­log­ics Eval­u­a­tion and Re­search, told at­ten­dees of the Bio­phar­ma Con­gress in Wash­ing­ton, DC on Mon­day.

“We’re get­ting ready to pi­lot that pro­gram,” Marks said, mak­ing clear the goal is to help ar­eas with high un­met needs.

I think the goal is to take a drug with some promise in the rare dis­ease space for dis­eases that don’t have al­ter­na­tives … and then take these prod­ucts, maybe they have break­through or ad­vanced ther­a­py des­ig­na­tion, they have promise and there is a prod­uct in de­vel­op­ment and not just a con­cept. And then give them the op­por­tu­ni­ty with not just chem­istry, man­u­fac­tur­ing and con­trols, which we have a pi­lot for, but al­low the clin­i­cal de­vel­op­ment to hap­pen in con­stant com­mu­ni­ca­tion and shar­ing of po­ten­tial re­sults be­fore a sub­mis­sion of an NDA or BLA. That’s the idea, is to move things as fast as pos­si­ble.

He said “it’s not un­like­ly in some of these rare dis­ease sit­u­a­tions that there will be hic­cups” and if those FDA-spon­sor con­ver­sa­tions can oc­cur in re­al time, they can re­solve those is­sues more quick­ly.

Celia Wit­ten

Marks stressed that he trusts his deputy Celia Wit­ten to find new tal­ent for the FDA’s re­tir­ing lead­er­ship as the agency tran­si­tions from its Of­fice of Tis­sues and Ad­vanced Ther­a­pies to the su­per-of­fice to be known as the Of­fice of Ther­a­peu­tic Prod­ucts, or OTP.

He al­so ex­plained how he’s look­ing in­to us­ing a Pro­ject Or­bis-like ap­proach to ex­pand­ing the ap­proval of gene and cell ther­a­pies through­out oth­er high-in­come coun­tries (e.g. UK, Japan, EU) as the FDA’s On­col­o­gy Cen­ter of Ex­cel­lence cur­rent­ly does for some new can­cer drugs and in­di­ca­tions.

“And we want to take it one step fur­ther for these rare dis­eases. For vac­cines, there’s WHO-pre­qual­i­fi­ca­tion, which is ba­si­cal­ly, WHO says this vac­cine has been li­censed in a ref­er­ence coun­try, it’s good enough for us, it should be good enough for you, and the idea is to quick­ly do that for gene ther­a­py so low­er-in­come coun­tries could po­ten­tial­ly make use of these ap­provals. Why is that im­por­tant? For some gene ther­a­pies, the on­ly way peo­ple will get treat­ment is if they get gene ther­a­py be­cause those coun­tries can­not af­ford sup­port­ive care, for in­stance,” Marks said, not­ing that “there may be ways to deal” with some of the mas­sive up­front costs.

When asked why there has been an in­crease in clin­i­cal holds from CBER, Marks not­ed mul­ti­ple caus­es in­clud­ing an in­crease in clin­i­cal tri­als, less ex­pe­ri­enced spon­sors in this cell and gene ther­a­py space, and

we see a va­ri­ety of dif­fer­ent type of INDs, some of which are miss­ing key pieces, and some­times those can be fixed with in­ter­ac­tive dis­cus­sions dur­ing the 30 days. But 30 days is not a lot of time if some­one doesn’t have a man­u­fac­tur­ing sec­tion to their IND [laugh­ter in the au­di­ence] — don’t laugh, don’t laugh, it hap­pens enough, we have a rule of threes that I wouldn’t tell you about it if it didn’t hap­pen at least three times … There are some cas­es where we have bona fide spon­sors who have is­sues that prob­a­bly could be re­solved with in­ter­ac­tive re­view where we just don’t have the band­width.

OTP is look­ing to bring on about 125 new staffers to help with the cell and gene ther­a­py re­views thanks to the lat­est it­er­a­tion of the user fee deals, but the mar­ket for tal­ent is fierce­ly com­pet­i­tive.

FDA’s out­go­ing OTAT di­rec­tor Wil­son Bryan re­cent­ly an­nounced his in­tent to re­tire but told End­points News on Mon­day that he’s look­ing for­ward to the next chal­lenge, and want­ed to hand off the reins of the of­fice to the next set of in­com­ing lead­er­ship as the tran­si­tion hap­pens.

Look­ing ahead, Bryan ex­pressed can­did fears that the agency may not end up pulling cell or gene ther­a­pies quick­ly when ap­proved un­der the ac­cel­er­at­ed path­way, and even when there might be not enough ev­i­dence of ef­fi­ca­cy from the con­fir­ma­to­ry tri­al.

He said he does think the ac­cel­er­at­ed path­way, which has on­ly been used once so far for a cell/gene ther­a­py, will be fre­quent­ly used and that the con­fir­ma­to­ry stud­ies could take years to con­firm ben­e­fit, es­pe­cial­ly if it’s a slow­ly de­vel­op­ing dis­ease.

“We’re go­ing to get in­to trou­ble with ac­cel­er­at­ed ap­proval for gene ther­a­pies if it takes years to tell us if some­thing works,” Bryan said. “Be­cause then that means it takes years to tell us if it doesn’t work.”

US regulators cleared an ultra-rare drug from Pharming Group, by way of Novartis, on Friday afternoon.

The Dutch biotech said the FDA greenlit leniolisib for an immunodeficiency disease known as activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome, or APDS. People 12 years and older can receive the oral drug, to be marketed as Joenja, beginning early next month, Pharming said, five days ahead of the decision deadline set by the FDA as part of a priority review.

Digital therapeutics company Better Therapeutics announced on Thursday that it’s cutting 35% of its staff as it awaits FDA clearance for its first product.

The company, which launched eight years ago, is one of a growing group of companies seeking a digital alternative to traditional medicine. The space saw a record $7.5 billion in investments in 2021, according to Chris Dokomajilar at DealForma, with uses spanning ADHD, PTSD and other indications. However, private insurers have been slow to hop on board.