FDA unsurprisingly brings down the hammer on Incyte's PD-1 — drawing a line for future accelerated approvals
It appears the PD-(L)1 honeymoon is finally over.
Incyte $INCY revealed late Friday the FDA has slammed its PD-1 retifanlimab — which was under priority review for locally advanced or metastatic squamous cell carcinoma of the anal canal — with a complete response letter, demanding “additional data” to show clinical benefit.
On one hand, the rejection should come as no surprise: Regulators spelled out the problems they saw with Incyte’s data package in no uncertain terms, raising concerns about the low response rates, lack of diversity and dearth of safety data in the single-arm trial. During the ensuing adcomm, the FDA’s cancer czar, Richard Pazdur, suggested the whole episode underscores the need to “reassess” how drugs get approved under the accelerated approval pathway without randomized studies.
The expert panel convened to advise on the BLA, echoing those concerns, voted 13-4 to defer an approval until more data are available from a placebo-controlled trial.
On the other, it signals an official shift in the agency’s handling of checkpoint blockers, if not cancer drugs in general: Five years after the landmark first approval for Merck’s Keytruda, and with eight PD-(L)1 drugs on the market, there will be no more easy passes.
Coming onto an increasingly crowded landscape in 2017 via a $900 million deal with MacroGenics, Incyte had elected to follow a strategy deployed by other latecomers like Regeneron. Instead of going head to head with the dominant players in major indications, the biotech zeroed in on niche cancer types with small patient populations desperate for new therapies.
Hervé Hoppenot, CEO of Incyte, held on to that fact in a statement.
“Patients with SCAC who have progressed after first-line chemotherapy currently do not have approved treatment options,” he said. “While we are not surprised with the FDA decision given the ODAC recommendation, we are disappointed.”
The company will be working with the FDA to “address feedback and determine next steps,” he added.
A few months ago, Incyte started enrolling for a 300-patient Phase III placebo-controlled study with the help of its Chinese partners at Zai Lab. But data aren’t scheduled to come out until the end of 2024.
In the meantime, physicians are also studying Merck’s Keytruda and Bristol Myers Squibb’s Opdivo for different subtypes of anal cancer.
For Mizuho analyst Mara Goldstein, the largely expected decision isn’t the end of the world for Incyte.
“Ultimately, we still view retifanlimab as a facilitator of clinical activity in combinations rather than a growth driver in and of itself,” she wrote in a note.