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.

Up­dat­ed: FDA re­mains silent on or­phan drug ex­clu­siv­i­ty af­ter last year's court loss

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

Big week for Alzheimer’s da­ta; As­traZeneca buys cell ther­a­py start­up; Dig­i­tal ther­a­peu­tics hits a pay­er wall; and more

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Am­gen, years be­hind ri­vals, says PhI obe­si­ty drug shows dura­bil­i­ty signs

While NBC ran “The Biggest Loser” for 17 seasons, deemed toxic by critics for the reality show’s punishing exercise and diet upheavals, researchers in pharmaceutical labs have been attempting to create prescription drugs that induce weight loss — and one pharma betting it can require less frequent dosing is out with a new crop of data.

Amgen was relatively late to the game compared to its approved competitor Novo Nordisk and green light-approaching rival Eli Lilly. But early data suggested Amgen’s AMG 133 led to a 14.5% weight reduction in the first few months of dosing, buoying shares earlier this fall, and now the California pharma is out with its first batch of durability data showing that figure fell slightly to 11.2% about 150 days after the last dose. Amgen presented at the 20th World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease on Saturday afternoon.

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Illustration: Assistant Editor Kathy Wong for Endpoints News

As mon­ey pours in­to dig­i­tal ther­a­peu­tics, in­sur­ance cov­er­age crawls



Talk therapy didn’t help Lily with attention deficit hyperactivity disorder, or ADHD. But a video game did.

As the 10-year-old zooms through icy waters and targets flying creatures on the snow-capped planet Frigidus, she builds attention skills, thanks to Akili Interactive Labs’ video game EndeavorRx. She’s now less anxious and scattered, allowing her to stay on a low dose of ADHD medication, according to her mom Violet Vu.

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Eli Lil­ly’s Alzheimer’s drug clears more amy­loid ear­ly than Aduhelm in first-ever head-to-head. Will it mat­ter?

Ahead of the FDA’s decision on Eli Lilly’s Alzheimer’s drug donanemab in February, the Big Pharma is dropping a first cut of data from one of the more interesting trials — but less important in a regulatory sense — at an Alzheimer’s conference in San Francisco.

In the unblinded 148-person study, Eli Lilly pitted its drug against Aduhelm, Biogen’s drug that won FDA approval but lost Medicare coverage outside of clinical trials. Notably, the study didn’t look at clinical outcomes, but rather the clearance of amyloid, a protein whose buildup is associated with Alzheimer’s disease, in the brain.

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US month­ly costs for biosim­i­lars 'sub­stan­tial­ly high­er' than Ger­many or Switzer­land, JA­MA re­search finds

As the global biologics market is expected to hit nearly the half-trillion-dollar mark this year, new JAMA research points to the importance of timely biosimilar entry, particularly as fewer biosimilars are entering the US than in Europe, and as monthly treatment costs for biosimilars were “substantially higher” in the US compared with Germany and Switzerland.

Among the three countries, biosimilar market share at launch was highest in Germany, but increased at the fastest rate in the US, the authors from the University of Zurich’s Institute of Law wrote in JAMA Network Open today.

Kirk Myers is shown in a still image from a new film series showcasing the efforts of HIV advocates funded by Gilead.

Gilead spot­lights HIV projects and the com­mu­ni­ty lead­ers dri­ving them in new mi­ni-doc­u­men­tary films

Gilead is going behind the scenes of some of the HIV initiatives it funds through grants in a new film series narrated by the people helming the projects.

The first four films and leaders come from across the US — Arianna Lint in Florida and Puerto Rico, Cleve Jones in San Francisco, June Gipson in Mississippi and Kirk Myers in Texas. Their HIV-focused efforts range from addressing unmet needs of the transgender community to delivering social services and high-quality health care in underserved communities.

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EMA pulls an opi­oid from the 1950s used to treat dry cough

The European Medicines Agency said Friday that it’s pulling from all European markets pholcodine-containing medicines, which are an opioid used in adults and children for the treatment of dry cough and in combo with other drugs as a treatment for cold and flu.

The decision to pull the medicines comes as the EMA points to the results from the recent ALPHO study, which show that use of pholcodine during the 12 months preceding anesthesia is linked to a risk of an anaphylactic reaction related to the neuromuscular blocking agents (NMBAs) used (with an adjusted OR of 4.2, and a 95% confidence interval of 2.5 to 6.9).

FDA's drug short­ages leader wants com­pa­nies to start re­port­ing in­creas­es in de­mand

It is no secret that drug shortages have been prevalent in 2022. Several major drug products, such as amoxicillin and Adderall, have been in short supply for several months and have led to members of Congress applying pressure on the FDA and HHS to resolve the situation.

Speaking at a webinar hosted by the Alliance for a Stronger FDA, Valerie Jensen, the associate director of the FDA’s Drug Shortage Staff, noted both the rise in quality-related issues and increased demand for some products. She called on companies to report such demand increases, even though they are not currently required to do so.