FDA slams In­cyte's PD-1 over sin­gle-arm study, low re­sponse and tri­al deaths

The ever-grow­ing PD-1 land­scape could see a new en­trant as an In­cyte pro­gram is slat­ed for an FDA de­ci­sion next month. But first, the biotech will have to get through an ad­comm Thurs­day, and brief­ing doc­u­ments from the agency ap­pear to cast doubt over how ef­fec­tive the can­di­date re­al­ly is.

Atop the is­sues is whether or not the com­pound reti­fan­limab has enough da­ta for an ac­cel­er­at­ed ap­proval, af­ter In­cyte treat­ed sec­ond-line pa­tients with squa­mous car­ci­no­ma of the anal canal in a sin­gle-arm tri­al. In­cyte’s study showed an over­all re­sponse rate of just 14% among 94 pa­tients, and the FDA says they’re un­sure whether this would cor­re­spond to a clin­i­cal ben­e­fit in a larg­er, place­bo-con­trolled tri­al.

The fig­ure fell well short of the 25% rate In­cyte told reg­u­la­tors they were seek­ing with the study, ac­cord­ing to doc­u­ments de­tail­ing the biotech’s Sep­tem­ber 2020 meet­ing. At that time, the FDA said the BLA pack­age would be stronger with da­ta from a big­ger tri­al and not­ed an ad­comm would be like­ly with just the one tri­al, but In­cyte sub­mit­ted their pitch two months lat­er.

Reg­u­la­tors al­so raised con­cerns over the tri­al’s de­mo­graph­ics, high­light­ing there was on­ly one Black pa­tient and four His­pan­ic or Lati­no pa­tients. And giv­en that HIV in­creas­es the risk of de­vel­op­ing this spe­cif­ic can­cer by about 15- to 35-fold, the FDA said it’s un­clear how the pro­gram could af­fect these pa­tients since on­ly nine HIV-pos­i­tive in­di­vid­u­als took part in the study.

Much like oth­er late­com­er PD-1 play­ers, In­cyte is tar­get­ing an in­di­ca­tion where the big­ger names have yet to win ap­proval. Ef­fi­ca­cy da­ta in the sec­ond-line set­ting for this can­cer are lim­it­ed and pa­tients gen­er­al­ly end up tak­ing more chemother­a­py if they progress af­ter their first round of treat­ments.

Nonethe­less, the FDA at­tempt­ed to draw some cross-tri­al com­par­isons be­tween In­cyte and oth­er small, ex­per­i­men­tal stud­ies. Look­ing at tri­als test­ing Op­di­vo, Keytru­da, and two dif­fer­ent chemo reg­i­mens, reg­u­la­tors found ORRs be­tween 17% and 33%, fig­ures nu­mer­i­cal­ly high­er than In­cyte’s re­port­ed fig­ure.

Among these tri­als, on­ly Op­di­vo’s en­rolled more than two dozen pa­tients, with Bris­tol My­ers Squibb hav­ing re­cruit­ed 37 par­tic­i­pants.

Gen­er­al­ly speak­ing, the FDA said, check­point in­hibitors us­ing ac­cel­er­at­ed ap­proval path­ways with ORR as their pri­ma­ry end­point have not gone on to con­firm clin­i­cal ben­e­fit in big­ger stud­ies. Out of the 76 check­point in­hibitor ap­provals grant­ed by the agency, 35 were giv­en an ac­cel­er­at­ed OK, the FDA said. Of those 35, nine of the 10 to fail con­fir­ma­to­ry tri­als had pre­vi­ous­ly used a sin­gle-arm study look­ing at ORR.

Those oth­er drugs had been green­lit main­ly due to their du­ra­tion of re­sponse fig­ures, but the FDA is un­cer­tain over In­cyte’s da­ta here as well. While most oth­er pro­grams had pro­longed re­spons­es last­ing years, In­cyte re­port­ed a me­di­an of on­ly 9.5 months among the 13 re­spon­ders.

There al­so ap­peared to be a dis­pute be­tween how the FDA and In­cyte in­ter­pret­ed the study’s safe­ty da­ta. In its re­port, In­cyte says there was on­ly one death con­nect­ed to a side ef­fect from the treat­ment, but reg­u­la­tors say there were 10 fa­tal treat­ment-re­lat­ed ad­verse events. The FDA said, how­ev­er, that the safe­ty pro­file was con­sis­tent with PD-1 ther­a­pies in oth­er set­tings.

Whether In­cyte’s next study is con­duct­ed to con­firm an ac­cel­er­at­ed ap­proval or if it’s part of a new pack­age fol­low­ing a CRL, the com­pa­ny plans to read out da­ta by the end of 2024.

Should reti­fan­limab win ap­proval, an­a­lysts have said it like­ly won’t be a block­buster. Tru­ist’s Srikri­pa De­varakon­da mod­eled peak world­wide sales in this par­tic­u­lar dis­ease at $43 mil­lion — al­though new in­di­ca­tions such as lung can­cer and Merkel cell car­ci­no­ma may push it to around $500 mil­lion. SVB Leerink, mean­while, is pro­ject­ing about $100 mil­lion in peak sales in 2030.

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

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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.

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.

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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.

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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.

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Ly­me vac­cine test com­ple­tion is pushed back by a year as Pfiz­er, Val­ne­va say they'll ad­just tri­al

Valneva and Pfizer have adjusted the end date for the Phase III study of their investigational Lyme disease vaccine, pushing it back by a year after issues at a contract researcher led to thousands of US patients being dropped from the test.

In a March 20 update to clinicaltrials.gov, Valneva and Pfizer moved the primary completion date on the trial, called VALOR, from the end of 2024 to the end of 2025.

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Stuart Peltz, former PTC Therapeutics CEO

Stu­art Peltz re­signs as PTC Ther­a­peu­tics CEO af­ter 25 years

Stuart Peltz, the longtime CEO of PTC Therapeutics who’s led the rare disease drug developer since its founding 25 years ago, is stepping down.

Succeeding him in the top job is Matthew Klein, who joined PTC in 2019 and was promoted to chief operating officer in 2022. In a call with analysts, he said the CEO transition has been planned for “quite some time” — in fact, as part of it, he gave the company’s presentation at the JP Morgan healthcare conference earlier this year.

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