An Incyte cancer drug that was turned down by the FDA two years ago was granted an unexpected approval Wednesday in a different type of cancer, a regulatory decision that now pits the new product in competition with already entrenched immunotherapies from Merck and partners Pfizer and EMD Serono.
Accelerated approval for the Incyte drug, retifanlimab, is for treatment of Merkel cell carcinoma, a rare form of skin cancer that’s aggressive and comes with a high risk of returning and spreading after its initial diagnosis. The FDA decision covers the treatment of adults with metastatic or recurrent locally advanced disease. Wilmington, Delaware-based Incyte will market the product under the name “Zynyz.”
Zynyz is a type of immunotherapy called a checkpoint inhibitor. The antibody is designed to block PD-1, a protein on immune cells that keeps them from recognizing and going after cancer cells. Merck checkpoint inhibitor Keytruda blocks the same target and its long list of approved indications already includes Merkel cell carcinoma. The EMD Serono and Pfizer drug Bavencio, a checkpoint inhibitor that blocks PD-L1 on cancer cells, became the first FDA-approved Merkel cell carcinoma therapy in 2017.
Incyte had aimed to go after a different type of cancer as the first indication for Zynyz. The company initially sought approval in squamous cell carcinoma of the anal canal, a rare cancer with no approved treatments after the disease has progressed following chemotherapy. Incyte applied for accelerated FDA approval based on data from an open-label, single-arm Phase 2 study. In 2021, an advisory committee voted to recommend a deferral on a regulatory decision until more data are available from a confirmatory study. The following month, the FDA rejected the Incyte drug and asked for more data. A Phase 3 study, which is testing Zynyz in combination with platinum-based chemotherapy as a potential first-line treatment for the disease, is ongoing.
While pursuing the anal cancer indication, Incyte also ran clinical trials for the drug in endometrial cancer, Merkel cell carcinoma, and non-small cell lung cancer. The Merkel cell carcinoma approval was a surprise because Incyte had not disclosed a biologics license application or a regulatory decision date, William Blair analyst Matt Phipps wrote in a research note. Incyte management told Phipps that the opportunity is to eventually expand the drug’s label to include other types of cancer as well as to combine the drug with other compounds in the Incyte pipeline. But Phipps said that while landing an approval in the anal cancer indication could provide a niche opportunity for Incyte, the opportunity beyond that is limited given the dominance of other checkpoint inhibitors across the major cancer indications.
FDA approval of Zynyz in Merkel cell carcinoma was based on the results of an open-label, single-arm study that evaluated the drug in 65 patients who had not previously received systemic therapy. The drug, dosed as a 30-minute infusion every four weeks, led to an objective response rate of 52%; the complete response rate was 18%. Results also showed that 76% of patients had a response that lasted six months or longer while 62% had a response that lasted for a year or more. The most common adverse reactions reported in the study include fatigue, muscle pain, severe itching, diarrhea, rash, fever, and nausea.
Incyte licensed Zynyz from MacroGenics, paying $150 million up front for global rights. With the drug’s first approval, the Rockville, Maryland-based biotech will receive a $15 million milestone payment from Incyte. The remaining development and regulatory milestones could reach up to $320 million; commercialization milestones could bring up to $330 million more.
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