With two concurrent FDA approvals, Incyte’s PD-1 inhibitor Zynyz has redeemed itself in anal cancer four years after an initial snub from the agency.
U.S. regulators have signed off on Zynyz, used in combination with platinum-based chemotherapy, for the first-line treatment of inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC), Incyte said Thursday.
The approval makes Zynyz the first treatment specifically approved in first-line anal cancer in the U.S., the company noted.
The go-ahead comes almost four years after the FDA turned down Incyte’s initial bid to introduce Zynyz as a single agent for patients with anal cancer following disease progression on, or who are intolerant to, platinum-based chemo. Now, together with the first-line nod, the FDA has also cleared Zynyz for that use, too.
Results from two clinical trials backed Incyte’s application. For the chemo combo in the first-line setting, Zynyz slashed the risk of progression or death by 37% versus chemo alone in the phase 3 POD1UM-303 trial. The study also showed a favorable trend at an interim analysis suggesting the addition of Zynyz may be able to reduce the risk of death by 30%, although the result didn’t cross the statistical significance bar. Additional overall survival follow-up is ongoing.
As for Zynyz monotherapy for platinum-refractory or -intolerant anal cancer, the single-arm POD1UM-202 trial linked the anti-PD-1 drug to a 14% objective response rate in 94 patients, with the duration of response lasting a median 9.5 months.
Back in 2021, the FDA and a group of external advisers had doubts about Zynyz in the previously treated anal cancer indication because of the small tumor response rate in light of some adverse events. The agency and the experts had wanted to wait for results from a confirmatory trial—namely, POD1UM-303—to make a decision.
SCAC, a rare disease, makes up 85% of anal cancer cases.
As Incyte CEO Hervé Hoppenot has previously told Fierce Pharma, the company does not expect Zynyz to be a major revenue driver. The drug was first approved by the FDA in 2023 for Merkel cell carcinoma, another rare type of skin cancer.
Hoppenot described Zynyz as an “opportunistic product” to enable first-line access to PD-1 drugs in some parts of the world outside the major U.S. and European markets.
In the first quarter of 2025, Zynyz brought in just $3 million in sales out of about $1 billion for the company as a whole.