FDA commissioner Rob Califf (Graeme Sloan/Sipa USA)(Sipa via AP Images)

FDA com­mis­sion­er on ac­cel­er­at­ed ap­proval re­forms: 'Need to ad­dress as soon as pos­si­ble'

As Con­gress punt­ed the user fee rid­ers on ac­cel­er­at­ed ap­proval path­way re­forms, FDA com­mis­sion­er Rob Califf made clear at a con­fer­ence this week that such re­forms need to hap­pen “as soon as pos­si­ble.”

The com­ment, com­ing near the end of a speech Califf made Mon­day at the Na­tion­al Or­ga­ni­za­tion for Rare Dis­or­ders’ an­nu­al con­fer­ence, fol­lowed sim­i­lar sug­ges­tions for re­forms as of­fi­cials at the FDA’s On­col­o­gy Cen­ter of Ex­cel­lence, who took to the NE­JM late last month ar­gu­ing for im­prove­ments to the agency’s abil­i­ty to ex­pe­di­tious­ly pull dan­gling ac­cel­er­at­ed ap­provals, which oc­cur when, on the rare oc­ca­sion, con­fir­ma­to­ry tri­als fail, but al­so bet­ter build­ing “qual­i­ty and ef­fi­cien­cy in­to the AA on-ramp.”

The OCE of­fi­cials made clear the need to en­sure con­fir­ma­to­ry tri­als are un­der­way when an ac­cel­er­at­ed ap­proval is grant­ed, as they showed a me­di­an time to with­draw­al of 3.8 years if the con­fir­ma­to­ry tri­al was on­go­ing at the time of ap­proval, com­pared with 7.3 years if such a tri­al had not been ini­ti­at­ed.

“I want to call your at­ten­tion to an is­sue that we need to ad­dress as soon as pos­si­ble – ac­cel­er­at­ed ap­provals,” Califf said Mon­day. “While the process is in­tend­ed to en­sure the in­tegri­ty of the da­ta and analy­ses, the fact is that ac­cel­er­at­ed ap­provals based on bio­mark­ers leave more un­cer­tain­ty about the true risk and ben­e­fit. And re­gard­less, many of these in­ter­ven­tions will be ap­proved based on a lim­it­ed time frame of a clin­i­cal tri­al. And yet, the po­ten­tial ef­fects, both ben­e­fits and risks, will be man­i­fest­ed over a life­time.”

The warn­ing shot comes as a re­cent HHS OIG re­port raised con­cerns about the bil­lions of dol­lars CMS spends on these ac­cel­er­at­ed ap­provals be­fore clin­i­cal ben­e­fit is con­firmed.

And the FDA’s OCE has sought to clean house when it comes to pulling ones that failed their con­fir­ma­to­ry tri­als. ODAC re­cent­ly eval­u­at­ed one dan­gling ac­cel­er­at­ed ap­proval, On­copep­tides’ Pepax­to, and one full ap­proval, Se­cu­ra Bio’s PI3K in­hibitor Copik­tra (du­velis­ib) as a third-line treat­ment for re­lapsed or re­frac­to­ry CLL or SLL with safe­ty ques­tions.

The out­side ex­perts vot­ed against keep­ing ei­ther drug on the mar­ket, al­though both spon­sors have since made clear that they won’t pull their drugs with­out a fight. The 2.5-day bat­tle over Co­vis’ de­layed ac­cel­er­at­ed ap­proval this week al­so serves as a re­minder of long and drawn out the with­draw­al process can be, even if the con­fir­ma­to­ry tri­al did not hit on its pri­ma­ry end­point.

While call­ing for a faster sys­tem of ev­i­dence gen­er­a­tion that con­firms ben­e­fits and risks for ac­cel­er­at­ed ap­provals more quick­ly, Califf al­so stressed ear­li­er in his speech the need to “ex­pand the sources, qual­i­ty, and types of da­ta we use to an­a­lyze and over­come” tri­al chal­lenges, in­clud­ing with re­al-world ev­i­dence and new bio­mark­ers.

Thanks to PDU­FA VII, the agency on Wednes­day an­nounced its new Ad­vanc­ing Re­al-World Ev­i­dence (RWE) pro­gram which will se­lect cer­tain par­tic­i­pat­ing spon­sors to meet with agency staff up to four ad­di­tion­al times be­fore pro­to­col de­vel­op­ment or study ini­ti­a­tion to dis­cuss the use of RWE in their de­vel­op­ment pro­grams.

The FDA this week al­so doled out 19 new grants and two new con­tracts to­tal­ing more than $38 mil­lion in funds over the next four years to sup­port clin­i­cal tri­als, nat­ur­al his­to­ry stud­ies and reg­u­la­to­ry sci­ence tools re­lat­ed to rare dis­eases.

And the agency is plan­ning for FY 2023 grants linked to its new Rare Neu­rode­gen­er­a­tive Dis­ease Grant Pro­gram which “does not have a fi­nal fund­ing amount,” but “it is ex­pect­ed that the bud­get for this pro­gram will be ap­prox­i­mate­ly $2 mil­lion and the ex­pect­ed num­ber of awards will be be­tween two to four grants,” the FDA said.

Has the mo­ment fi­nal­ly ar­rived for val­ue-based health­care?

RBC Capital Markets’ Healthcare Technology Analyst, Sean Dodge, spotlights a new breed of tech-enabled providers who are rapidly transforming the way clinicians deliver healthcare, and explores the key question: can this accelerating revolution overturn the US healthcare system?

Key points

Tech-enabled healthcare providers are poised to help the US transition to value, not volume, as the basis for reward.
The move to value-based care has policy momentum, but is risky and complex for clinicians.
Outsourced tech specialists are emerging to provide the required expertise, while healthcare and tech are also converging through M&A.
Value-based care remains in its early stages, but the transition is accelerating and represents a huge addressable market.

Lat­est on ul­tra-rare dis­ease ap­proval; Pos­i­tive, if mixed, signs for Bio­gen's ALS drug; Clay Sie­gall finds a new job; 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.

Over the last four years, we’ve honored 80 women whose extraordinary accomplishments have changed the game in biopharma R&D. You can now nominate someone to be highlighted in this year’s special report. Details are here.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

FDA ad­vi­sors unan­i­mous­ly rec­om­mend ac­cel­er­at­ed ap­proval for Bio­gen's ALS drug

A panel of outside advisors to the FDA unanimously recommended that the agency grant accelerated approval to Biogen’s ALS drug tofersen despite the drug failing the primary goal of its Phase III study, an endorsement that could pave a path forward for the treatment.

By a 9-0 vote, members of the Peripheral and Central Nervous System Drugs Advisory Committee said there was sufficient evidence that tofersen’s effect on a certain protein associated with ALS is reasonably likely to predict a benefit for patients. But panelists stopped short of advocating for a full approval, voting 3-5 against (with one abstention) and largely citing the failed pivotal study.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

FDA spells out how can­cer drug de­vel­op­ers can use one tri­al for both ac­cel­er­at­ed and full ap­provals

The FDA’s Oncology Center of Excellence has been a bright spot within the agency in terms of speeding new treatments to patients. That flexibility was on full display this morning as FDA released new draft guidance spelling out exactly how oncology drug developers can fulfill both the accelerated and full approval’s requirements with just a single randomized controlled trial.

While Congress recently passed legislation that will allow FDA to require confirmatory trials to be recruiting and ongoing prior to granting an accelerated approval, the agency is now making clear that the initial trial used to win the AA, if designed appropriately, can also serve as the trial for converting the accelerated approval into a full approval.

Clay Siegall, Morphimmune CEO

Up­dat­ed: Ex-Seagen chief Clay Sie­gall emerges as CEO of pri­vate biotech

Clay Siegall will be back in the CEO seat, taking the helm of a private startup working on targeted cancer therapies.

It’s been almost a year since Siegall resigned from Seagen, the biotech he co-founded and led for more than 20 years, in the wake of domestic violence allegations by his then-wife. His eventual successor, David Epstein, sold the company to Pfizer in a $43 billion deal unveiled last week.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

Sijmen de Vries, Pharming CEO

FDA ap­proves Pharm­ing drug for ul­tra-rare im­mun­od­e­fi­cien­cy dis­ease

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.

No­vo Nordisk oral semaglu­tide tri­al shows re­duc­tion in blood sug­ar, plus weight loss

Novo Nordisk is testing higher levels of its oral version of its GLP-1, semaglutide, and its type 2 diabetes trial results released today show reductions in blood sugar as well as weight loss.

In the Phase IIIb trial, Novo compared its oral semaglutide in 25 mg and 50 mg doses with the 14 mg version that’s currently the maximum approved dose. The trial looked at how the doses compared when added to a stable dose of one to three oral antidiabetic medicines in people with type 2 diabetes who were in need of an intensified treatment.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

Eu­ro­pean Com­mis­sion de­lays pro­pos­al for ma­jor changes to phar­ma leg­is­la­tion

The European Commission has once again delayed the release of its proposal for an overhaul of the continent’s pharmaceutical legislation.

The release, previously anticipated on March 29, will occur “slightly later” than expected due to the “very busy College agendas of the last few weeks,” a Commission spokesperson told Endpoints News via email.

While the agency hasn’t provided an updated timeline, the spokesperson said the agenda is “always indicative and adoption dates of Commission proposals may change any time, especially when these proposals concern reforms of complex legislations of major importance.”

In­cyte wins ac­cel­er­at­ed ap­proval for PD-1 in rare skin can­cer

Incyte touted an accelerated approval for its PD-1 retifanlimab in a rare skin cancer on Wednesday, roughly a year and a half after the drug suffered a rejection in squamous cell carcinoma of the anal canal (SCAC).

Retifanlimab, marketed as Zynyz, was approved for metastatic or recurrent locally advanced Merkel cell carcinoma (MCC), a fast-growing skin cancer typically characterized by a single, painless nodule. It’s roughly 40 times rarer than melanoma, according to the nonprofit Skin Cancer Foundation — but incidence is growing, particularly among older adults, Incyte said in its announcement.