Incyte's Zynyz® Approved by FDA as First-Line Treatment for Advanced Anal Cancer in the US

WILMINGTON, DE, USA I May 15, 2025 I Incyte has announced the approval of Zynyz® (retifanlimab-dlwr) by the U.S. Food and Drug Administration (FDA). Zynyz, a humanized monoclonal antibody targeting programmed death receptor-1 (PD-1), is approved for use alongside carboplatin and paclitaxel, a platinum-based chemotherapy, for the initial treatment of adult patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC). Furthermore, Zynyz has also been approved as a standalone treatment option for adults with locally recurrent or metastatic SCAC who have either progressed on or shown intolerance to platinum-based chemotherapy.

Hervé Hoppenot, Chief Executive Officer of Incyte, hailed the FDA's approval as a significant milestone. He emphasized the importance of providing effective combination and monotherapy treatment alternatives to patients with advanced anal cancer, a field that has seen little innovation in recent decades. Hoppenot expressed pride in the efforts of Incyte's scientific and development teams, which have resulted in the delivery of the first PD-1 inhibitor approved for U.S. patients with SCAC.

The approval followed a Priority Review process and was based on data from two pivotal clinical trials. The Phase 3 POD1UM-303/InterAACT2 trial explored the combination of Zynyz with platinum-based chemotherapy in adult patients with metastatic or inoperable locally recurrent SCAC who had not undergone systemic chemotherapy treatment before. Meanwhile, the Phase 2 POD1UM-202 trial assessed Zynyz as a monotherapy for patients with locally advanced or metastatic SCAC that had progressed despite prior platinum-based chemotherapy treatment or in cases of intolerance.

The POD1UM-303/InterAACT2 trial demonstrated a clinically meaningful and statistically significant reduction of 37% in the risk of disease progression or death among patients receiving the Zynyz and chemotherapy combination. These patients experienced a median progression-free survival (PFS) of 9.3 months, compared to 7.4 months in the placebo combination group. Moreover, there was a 6.2-month improvement in median overall survival (OS) at an interim analysis, with OS follow-up still ongoing. Serious adverse effects were reported in 47% of patients treated with Zynyz combined with chemotherapy, with sepsis, pulmonary embolism, diarrhea, and vomiting being the most frequent.

Dr. Marwan Fakih of City of Hope remarked on the significance of this approval, highlighting the historically poor five-year survival rates and limited treatment options for patients with advanced anal cancer. He emphasized the potential of Zynyz to serve as a meaningful new option by significantly improving progression-free survival when added to platinum-based chemotherapy.

As for Zynyz monotherapy, the POD1UM-202 study showed an objective response rate of 14% and a disease control rate of 49%. The safety profile of Zynyz was consistent with expectations for PD-1 inhibitors, without compromising control of HIV infection. Serious adverse reactions were noted in 40% of patients, including non-urinary tract infection, perineal pain, abdominal pain, anemia, hemorrhage, diarrhea, fever, urinary tract infection, musculoskeletal pain, and difficulty breathing.

David Winterflood, CEO of the Anal Cancer Foundation, highlighted the approval of Zynyz as a significant advancement for SCAC treatment. He stressed the importance of raising awareness and understanding of anal cancer, often overshadowed by other types of cancer, and providing patients with improved treatment options.

Beyond the approval in the U.S., Incyte has also submitted a Type II variation Marketing Authorization Application to the European Medicines Agency and a Japanese New Drug Application, accepted by the Pharmaceuticals and Medical Devices Agency, for retifanlimab in advanced SCAC.

Incyte also launched IncyteCARES, a support program aimed at assisting eligible U.S. patients prescribed Zynyz. The program offers financial assistance, personalized support, ongoing education, and additional resources to help patients access treatment.