Retifanlimab

WILMINGTON, DE, USA I May 15, 2025 I Incyte (Nasdaq:INCY) today announced that the U.S. Food and Drug Administration (FDA) has approved Zynyz ® (retifanlimab-dlwr), a humanized monoclonal antibody targeting programmed death receptor-1 (PD-1), in combination with carboplatin and paclitaxel (platinum-based chemotherapy) for the first-line treatment of adult patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC). In addition, the FDA granted approval for Zynyz as a single agent for the treatment of adult patients with locally recurrent or with metastatic SCAC with disease progression on or intolerance to platinum-based chemotherapy. “The FDA approval of Zynyz marks a pivotal moment, bringing effective combination and monotherapy treatment options to patients with advanced anal cancer after decades of limited innovation,” said Hervé Hoppenot, Chief Executive Officer, Incyte. “At Incyte, we focus our efforts where we can make the biggest impact for patients. I am proud of our scientists and development teams for their perseverance in delivering the first approved PD-1 inhibitor to U.S. patients with SCAC.” The Priority Review and FDA approval of the supplemental Biologics License Application (sBLA) for Zynyz was based on data from two trials: the Phase 3 POD1UM-303/InterAACT2 trial evaluating Zynyz in combination with platinum-based chemotherapy (carboplatin-paclitaxel) in adult patients with metastatic or inoperable locally recurrent SCAC not previously treated with systemic chemotherapy, and the Phase 2 POD1UM-202 trial evaluating Zynyz monotherapy in previously treated patients with locally advanced or metastatic SCAC who have progressed on or were intolerant of platinum-based chemotherapy. Results from POD1UM-303/InterAACT2, featured at a Presidential Symposium on Practice-Changing Trials at the European Society for Medical Oncology (ESMO) in 2024 , showed a clinically meaningful and statistically significant 37% reduction in the risk of progression or death ( P =0.0006). Patients in the Zynyz and chemotherapy combination group achieved a median progression-free survival (PFS) of 9.3 months compared to 7.4 months for patients in the placebo combination group. Additionally, a 6.2-month improvement in median overall survival (OS) was observed ( P =0.0273) at an interim analysis; OS follow-up is ongoing. No new safety signals were observed. Serious adverse reactions occurred in 47% of patients receiving Zynyz in combination with chemotherapy. The most frequent serious adverse reactions (≥ 2% of patients) were sepsis (3.2%), pulmonary embolism (3.2%), diarrhea (2.6%) and vomiting (2.6%). “Patients with inoperable locally recurrent or metastatic anal cancer have historically faced poor five-year survival rates and limited treatment options. 1 The POD1UM data highlight the potential of Zynyz to be a meaningful new option, and notably demonstrate that the addition of Zynyz to platinum-based chemotherapy significantly improves progression-free survival,” said Marwan Fakih, M.D., Professor, Medical Oncology & Therapeutics Research, Associate Director, Clinical Sciences, Medical Director, Briskin Center for Clinical Research, Division Chief, GI Medical Oncology, Co-Director, Gastrointestinal Cancer Program, City of Hope. “This approval marks an important advancement as it makes a new treatment approach available for this challenging cancer.” The Zynyz monotherapy approval is based on results from the POD1UM-202 study which demonstrated that treatment with Zynyz monotherapy produced an objective response rate (ORR) of 14% and disease control rate of 49%. Zynyz demonstrated a safety profile as expected of a PD-1 inhibitor with no loss of human immunodeficiency virus (HIV) infection control. 2 Serious adverse reactions occurred in 40% of patients receiving Zynyz. The most frequent serious adverse reactions (≥ 2% of patients) were non-urinary tract infection, perineal pain, abdominal pain, anemia, hemorrhage, diarrhea, pyrexia, urinary tract infection, musculoskeletal pain and dyspnea. “Patients with anal cancer often face a troubling lack of public awareness and understanding when it comes to risk factors, symptoms and their overall cancer journey,” said David Winterflood, Chief Executive Officer of the Anal Cancer Foundation. “The approval of Zynyz marks a step forward for advanced SCAC treatment, brings attention to a long-overlooked condition with limited treatment options and offers patients whose anal cancer has returned or spread an option to treat their disease.” In addition to the sBLA in the U.S., Incyte submitted a Type II variation Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for retifanlimab in advanced SCAC and a Japanese New Drug Application (J-NDA) which was accepted by the Pharmaceuticals and Medical Devices Agency (PMDA) for retifanlimab in advanced SCAC. Incyte is committed to supporting patients and removing barriers to access medicines. Eligible patients in the U.S. who are prescribed Zynyz have access to IncyteCARES (Connecting to Access, Reimbursement, Education and Support), a comprehensive program offering personalized patient support, including financial assistance and ongoing education and additional resources. More information about IncyteCARES is available by visiting www.incytecares.com or calling 1-855-452-5234, Monday through Friday, from 8 a.m. to 8 p.m. ET. About Squamous Cell Carcinoma of the Anal Canal (SCAC) SCAC is the most common type of anal cancer, making up 85% of cases. 3 It is a rare disease for which the incidence is increasing approximately 3% per year. 4 About 90% of cases are associated with human papillomavirus (HPV) infection—the number one risk factor for anal cancer. 5 HIV is an important amplifier of anal cancer, as people with HIV are 25 to 35 times more likely to develop it. 6,7 Anal cancer shares many of the same symptoms as non-cancerous conditions, such as hemorrhoids—including pain, itching, a lump or mass and changes in bowel movements—and as a result can go undetected leading to the majority of patients presenting with locally advanced disease. 2,8 More information about SCAC is available by visiting www.analcancer.com . About POD1UM The POD1UM (PD1 Clinical Program in Multiple Malignancies) clinical trial program for retifanlimab includes POD1UM-303 , POD1UM-202 and several other Phase 1, 2 and 3 studies for patients with solid tumors, including a registration-directed trial evaluating retifanlimab in combination with platinum-based chemotherapy for patients with non-small cell lung cancer. About Zynyz ® (retifanlimab-dlwr) Zynyz ® (retifanlimab-dlwr) is a humanized monoclonal antibody targeting programmed death receptor-1 (PD-1), indicated in combination with carboplatin and paclitaxel (platinum-based chemotherapy) for the first-line treatment of adult patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC) and as a single agent for the treatment of adult patients with locally recurrent or metastatic SCAC with disease progression or intolerance to platinum-based chemotherapy in the U.S. Zynyz is also indicated for the treatment of adult patients with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC) in the U.S. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Zynyz is marketed by Incyte in the United States. In 2017, Incyte entered into an exclusive collaboration and license agreement with MacroGenics, Inc. for global rights to retifanlimab. Please see the full Prescribing Information, including the Medication Guide , for Zynyz. You may also report side effects to the FDA http://www.fda.gov/medwatch or to Incyte Corporation at 1-855-463-3463. About Incyte A global biopharmaceutical company on a mission to Solve On. , Incyte follows the science to find solutions for patients with unmet medical needs. Through the discovery, development and commercialization of proprietary therapeutics, Incyte has established a portfolio of first-in-class medicines for patients and a strong pipeline of products in Oncology and Inflammation & Autoimmunity. Headquartered in Wilmington, Delaware, Incyte has operations in North America, Europe and Asia. For additional information on Incyte, please visit Incyte.com or follow us on social media: LinkedIn , X , Instagram , Facebook , YouTube . SOURCE: Incyte

iStock, Bo Shen The FDA also approved the use of Zynyz as a monotherapy for patients with squamous cell carcinoma of the anal canal who are intolerant to platinum chemotherapy or whose disease has progressed. Incyte on Thursday successfully expanded the label of its cancer therapy Zynyz, opening up its use as a first-line therapy for patients with squamous cell carcinoma of the anal canal. Zynyz, first approved in 2023 for metastatic, recurrent or locally advanced Merkel cell carcinoma, is an intravenous PD-1 inhibitor that forms a substantial part of Incyte’s cancer portfolio. In an April 29 note to investors, in reaction to the company’s Q1 results, analysts at Truist noted that Zynyz—alongside the lymphoma drug Monjuvi—will help account for the company’s 2025 oncology sales forecast of $415 million to $455 million. Thursday’s approval covers the use of Zynyz in combination with carboplatin and paclitaxel as a frontline treatment option for patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC). The FDA also signed off on Zynyz as a monotherapy for patients whose disease has progressed or who are otherwise intolerant to platinum-based chemotherapy. The expansion snatched victory from the jaws of defeat, as the FDA rejected Zynyz in SCAC in 2021. In a note Friday morning, Leerink Partners wrote that “Zynyz + chemo demonstrated a clear benefit over 1L standard of care carboplatin–paclitaxel...likely helping to dispel former FDA concerns on the efficacy profile.” The approval is a “pivotal moment” for the SCAC space, CEO Hervé Hoppenot said, “bringing effective combination and monotherapy treatment options.” Zynyz is the first PD-1 blocker in the U.S. to be approved for the indication, according to Hoppenot. Backing Zynyz’s approval are data from the Phase III POD1UM-303 trial. Incyte presented results from this study at the September 2024 European Society of Medical Oncology (ESMO) meeting, touting a 37% reduction in the risk of disease progression or death in patients treated with Zynyz plus a platinum-based chemotherapy regimen versus chemotherapy alone. Incyte at the time called this effect “clinically meaningful.” The ESMO readout also demonstrated improvements in overall survival and overall response rates in patients treated with the Zynyz combo. Incyte is also seeking approval for Zynyz in SCAC in the European Union and Japan. Zynyz’s label expansion comes weeks after Incyte announced Q1 earnings that William Blair labeled “solid” in an April 29 note. The company made $1.053 billion in the quarter, a 20% year-on-year increase and a comfortable beat over the $990 million consensus expectation. Jakafi, a kinase inhibitor, remained Incyte’s strongest asset. The drug brought in $709 million in Q1, which surpassed the $643 analyst estimate. With this strong start to the year, the company raised its full-year guidance for the drug from $2.95 billion to $3 billion. Incyte’s heavy reliance on Jakafi, however, is double-edged, according to William Blair. “While we believe that Jakafi remains the best-in-class therapy in some approved indications, there is emerging competition and potential for a novel therapy to take market share,” the analysts wrote. Competition and impending loss of exclusivity—key patents are expected to expire in late 2028—are “ongoing concerns,” as per William Blair.