Sometimes, the second time is the charm. After a 2021 complete response letter from the FDA for approval in a different indication, the agency has now greenlighted Incyte’s intravenous drug, Zynyz. The drug got the go-ahead through the FDA’s accelerated approval pathway for metastatic or recurrent locally advanced Merkel cell carcinoma (MCC).
Zynyz is a checkpoint inhibitor immunotherapy that targets PD-1. Its approval marks the eight checkpoint inhibitor to hit the market and the third indicated for metastatic MCC, joining Merck & Co.’s PD-1 inhibitor Keytruda and Pfizer and Merck KGaA’s PD-L1 directed Bavencio.
The approval was based on data from the POD1UM-201 trial, a single-arm study that tested the drug in adult patients who had not received prior systemic therapy. Zynyz had an objective response rate of 52%. Twelve patients, or 18% of patients, saw a complete response, and 34% (22 patients) achieved partial response. The duration of response in these patients ranged from 1.1 month to more than 24.9 months, with 76% responding for six months or longer and 62% responding for 12 months or longer.
In the trial, serious adverse reactions occurred in 22% of patients, with 11% permanently discontinuing treatment due to adverse reactions.
The nod came as a surprise to industry watchers, as the company hadn’t announced its application filing or a decision date, analysts at William Blair pointed out in a note to clients. The analysts see “limited opportunity” for Zynyz given the prevalence of other PD-1 and PD-L1 checkpoint inhibitors. However, an approval for front-line squamous cell anal carcinoma (SCAC) would provide a “niche opportunity” for the company.
That indication is what Incyte originally went after in 2021, when an FDA advisory committee flagged several concerns and ultimately asked for more data before it could recommend approval. The company is still trialing the drug in that setting as well as other indications through its POD1UM clinical trial program. That includes phase 1, 2 and 3 studies testing Zynyz as a monotherapy to treat microsatellite instability-high endometrial cancer and SCAC, plus in combination with chemotherapy for patients with SCAC and non-small cell lung cancer.
Incyte will “make decisions about potential future regulatory filings based upon results from our registration-directed trials,” a company spokesperson said in an emailed response to Fierce Pharma.
MCC is a rare cancer type, affecting less than one per 100,000 people in the U.S., but cases are rapidly rising especially in adults over the age of 65, according to Incyte's press release announcing the approval. The ongoing phase 2 POD1UM-201 trial will act as the confirmatory trial, the spokesperson said. The study has an estimated completion date of June 2024, according to its clinical trial record. The drug's full approval is contingent on that trial and the clinical benefit it shows.
As for the price point, Zynyz’s monthly price tag will be “comparable” to other agents in the class that are on the market, the spokesperson said. Keytruda has a list price of $10,683 for each dose when given every three weeks and $21,367 for each dose when given every six weeks. However, Incyte is “committed” to working with U.S. insurance providers to ensure greater access, according to the release.