FDA as­sem­bles ad­comm to re­view GSK's Jem­per­li tri­al plans in rec­tal can­cer

The FDA’s On­co­log­ic Drugs Ad­vi­so­ry Com­mit­tee will meet this Thurs­day to dis­cuss whether pro­posed stud­ies would sup­port an ac­cel­er­at­ed ap­proval for GSK’s Jem­per­li in rec­tal can­cer — de­spite ini­tial con­cerns about the tri­al plans.

GSK’s PD-1 block­er Jem­per­li, al­so known as dostar­limab, was first ap­proved back in 2021 for a spe­cif­ic sub­set of re­cur­rent or ad­vanced en­dome­tri­al can­cer pa­tients who have a ge­net­ic fea­ture called dMMR, or de­fi­cient mis­match re­pair. The la­bel was ex­pand­ed months lat­er to in­clude all adults with dMMR re­cur­rent or ad­vanced sol­id tu­mors who have pro­gressed or stag­nat­ed on ear­li­er ther­a­py.

Now, GSK is look­ing to reach “lo­cal­ly ad­vanced, treat­ment-naïve mis­match re­pair de­fi­cien­cy/mi­crosatel­lite in­sta­bil­i­ty-high rec­tal can­cer” — and it’s hop­ing the re­sults from two pro­posed sin­gle-arm tri­als will sup­port an ac­cel­er­at­ed ap­proval. One of those tri­als would en­roll 30 pa­tients in a sin­gle-cen­ter tri­al, and the oth­er would en­roll 100 pa­tients across mul­ti­ple tri­al sites.

ODAC is con­ven­ing on Thurs­day to dis­cuss the pro­posed tri­als, and on Tues­day, reg­u­la­tors re­leased brief­ing doc­u­ments spelling out their con­cerns.

Af­ter dis­cussing the plans, ad­comm mem­bers will vote on the ques­tion: “Will the da­ta from the pro­posed sin­gle arm tri­als en­rolling a to­tal of 130 pa­tients be suf­fi­cient to char­ac­ter­ize the ben­e­fits and risks of dostar­limab in the cu­ra­tive in­tent set­ting for pa­tients with dMMR/MSI-H LARC?”

While GSK has ar­gued that the rar­i­ty of the dis­ease would make ran­dom­ized tri­als in the spe­cif­ic sub­set of lo­cal­ly ad­vanced rec­tal can­cer “in­fea­si­ble,” the FDA not­ed in its brief­ing doc­u­ments that the agency has “gen­er­al­ly re­quired ran­dom­ized tri­als to sup­port the safe­ty and ef­fi­ca­cy eval­u­a­tion of dostar­limab.”

The FDA al­so in­clud­ed a brief analy­sis of GSK’s pro­posed end­points for the tri­als, in­clud­ing an in­ter­me­di­ate end­point of clin­i­cal com­plete re­sponse rate (cCR) at 12 months.

How­ev­er, FDA not­ed:

The use of cCR in LARC clin­i­cal de­ci­sion-mak­ing is based on small, most­ly ret­ro­spec­tive, un­con­trolled stud­ies that vary in de­sign and oth­er im­por­tant fac­tors (e.g., chemother­a­py reg­i­men used, ra­dio­ther­a­py pro­to­col, mon­i­tor­ing pro­to­col for as­sess­ment of cCR, method of as­sess­ing clin­i­cal cCR, pa­tient se­lec­tion, etc.,) thus lim­it­ing the in­ter­pretabil­i­ty of find­ings.

Reg­u­la­tors con­tin­ued that while pre­lim­i­nary da­ta showed a cCR rate of 100% at one site, “it is un­clear whether these re­sults will be replic­a­ble across more sites,” not­ing the pos­si­bil­i­ty of vari­abil­i­ty in lo­cal ex­per­tise. Al­so from the doc­u­ments:

GSK pro­pos­es to use cCR36 as as­sessed by the in­ves­ti­ga­tor and event-free sur­vival at 36 months as as­sessed by ICR to ver­i­fy the clin­i­cal ben­e­fit of dostar­limab if ac­cel­er­at­ed ap­proval is grant­ed. Time-to-event end­points are chal­leng­ing to in­ter­pret in sin­gle-arm tri­als, and, giv­en the het­ero­gene­ity of the da­ta de­scrib­ing re­lapse in LARC, com­par­i­son to his­tor­i­cal con­trol may be chal­leng­ing.

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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.

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 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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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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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.

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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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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