Incyte Prepares for FDA Revisit with New Zynyz Data in Rare Anal Cancer

Incyte has announced promising late-stage results for its PD-1 inhibitor, Zynyz, in treating squamous cell carcinoma of the anal canal (SCAC). Three years ago, the U.S. Food and Drug Administration (FDA) requested additional data on the drug, leading to a Phase 3 trial named POD1UM-303. This trial examined the combination of Zynyz and chemotherapy in patients with inoperable, locally advanced, or metastatic SCAC.

The results of the POD1UM-303 trial revealed that the combination therapy met its primary endpoint, achieving a progression-free survival of 9.3 months compared to 7.39 months for chemotherapy with a placebo. This difference is statistically significant (p=0.0006). Furthermore, there was a notable trend towards improved overall survival rates with the Zynyz combination, although the data is still considered immature. Importantly, the addition of Zynyz to chemotherapy did not introduce new safety concerns, indicating a favorable safety profile for the treatment.

Incyte had initially filed for FDA approval of Zynyz for SCAC in January 2021, using data from a single-arm Phase 2 trial under a priority review pathway. However, the FDA issued a Complete Response Letter (CRL) in July 2021, requesting more clinical benefit data. Despite this setback, Zynyz received FDA approval in 2023 for treating metastatic or recurrent locally advanced Merkel cell carcinoma.

The overall response rate (ORR) was a critical issue during Incyte’s first attempt to secure approval for Zynyz in SCAC. In the initial Phase 2 trial, Zynyz achieved a 14% ORR among 94 patients. However, the new data from the placebo-controlled Phase 3 study, which included 308 participants, showed a significant improvement. The treatment arm achieved a 55.8% ORR compared to 44.2% for the chemotherapy plus placebo group, yielding a statistically significant p-value of 0.0129.

Incyte's CEO Hervé Hoppenot announced plans to refile for FDA approval of Zynyz in SCAC by the end of the year, with a potential market launch anticipated next fall. Hoppenot emphasized that Zynyz is the only PD-1 inhibitor studied in chemotherapy-naïve SCAC patients to date. However, he tempered expectations by stating that Zynyz is not expected to be a multibillion-dollar product, given the relatively limited market size for this indication. Instead, Zynyz is seen as a stepping stone for future clinical trials and a contributor to short-term revenue.

Beyond Zynyz, Incyte is also focusing on other promising assets in its pipeline. One notable candidate is INCB123667, a small molecule CDK2 inhibitor currently undergoing clinical proof-of-concept studies for solid tumors. Additionally, Incyte has decided to discontinue four early-stage drug candidates due to shifting treatment landscapes and evolving internal priorities. These discontinued candidates include two oral small molecule PD-L1 inhibitors, a TIM-3 monoclonal antibody, and a LAG-3xPD-1 bispecific antibody.

SCAC is a rare but significant disease, accounting for 3% of all digestive system cancers. It is often associated with human papillomavirus (HPV) and HIV infections. Incyte’s ongoing efforts to address this and other cancers highlight the company's commitment to developing innovative treatments in oncology.