Incyte’s Zynyz Secures First-Line Approval in Anal Cancer, Marking a Milestone for PD-1 Therapy in Rare Tumor Type
In a significant development for the treatment of a rare and underserved cancer type, Incyte Corporation announced on Thursday that the U.S. Food and Drug Administration (FDA) has approved an expanded indication for its anti-PD-1 immunotherapy Zynyz (retifanlimab-dlwr). This regulatory milestone makes Zynyz the first programmed death receptor-1 (PD-1) inhibitor to be authorized in the U.S. for the first-line treatment of advanced squamous cell carcinoma of the anal canal (SCAC), a form of cancer that affects several thousand individuals each year but has historically seen limited innovation in systemic therapies.
The FDA’s decision allows the use of Zynyz in combination with carboplatin and paclitaxel for the frontline treatment of adult patients with inoperable locally recurrent or metastatic SCAC. The agency also greenlit the drug as a monotherapy for patients with SCAC whose disease has progressed on—or who are unable to tolerate—platinum-based chemotherapy. This double nod offers oncologists new tools in both the combination and salvage therapy settings, potentially reshaping the standard of care for this difficult-to-treat population.
From Setback to Breakthrough: A Reversal of Fortune
Zynyz’s approval for SCAC represents a major turnaround for Incyte after a previous regulatory setback. The FDA had declined to approve the therapy for this indication in 2021, citing concerns over the efficacy data. However, this most recent approval reflects the agency’s satisfaction with new, more robust evidence presented by Incyte—particularly results from the pivotal Phase III POD1UM-303 trial.
In a note to clients on Friday morning, analysts at Leerink Partners highlighted that the updated data package helped address the FDA’s prior reservations. “Zynyz + chemo demonstrated a clear benefit over 1L standard of care carboplatin–paclitaxel,” the firm wrote. “This likely helped dispel former FDA concerns on the efficacy profile.”
Incyte’s CEO Hervé Hoppenot celebrated the regulatory win, emphasizing its broader significance within the field of oncology. “This approval is a pivotal moment for the SCAC treatment landscape,” Hoppenot said. “It brings effective combination and monotherapy treatment options to patients who have had limited systemic therapeutic alternatives. Zynyz now stands as the first PD-1 inhibitor to be approved in the U.S. specifically for this indication.”
A Closer Look at the Data: POD1UM-303
The FDA’s green light was largely based on clinical data from the Phase III POD1UM-303 trial, a randomized study evaluating the efficacy and safety of Zynyz in combination with platinum-based chemotherapy. Incyte presented the topline findings at the European Society for Medical Oncology (ESMO) Congress in September 2024. The results showed that the combination of Zynyz with carboplatin and paclitaxel reduced the risk of disease progression or death by 37% compared to chemotherapy alone—a statistically and clinically meaningful result.
In addition to the improvement in progression-free survival, the Zynyz regimen also delivered favorable outcomes in secondary endpoints, including overall survival and overall response rate. Patients receiving the combination therapy experienced deeper and more durable responses, which could ultimately translate into longer-term survival benefits for a population in urgent need of better treatments.
Addressing an Unmet Need in a Rare Cancer
Squamous cell carcinoma of the anal canal is a rare malignancy, with an estimated 9,000 new cases diagnosed annually in the United States. Although early-stage disease is typically managed with chemoradiation, patients with recurrent or metastatic SCAC have limited systemic treatment options, and outcomes remain poor. The current frontline standard of care—carboplatin plus paclitaxel—offers modest benefits, and until now, no immunotherapies had been formally approved for use in this setting.
PD-1 inhibitors have revolutionized cancer treatment in multiple tumor types, but their development in anal cancer has lagged behind due to the disease’s rarity and clinical complexity. Incyte’s success with Zynyz in SCAC not only fills an important treatment gap but also highlights the growing relevance of checkpoint inhibitors in treating virally associated cancers. A significant proportion of SCAC cases are linked to chronic infection with human papillomavirus (HPV), which creates an immunologically “hot” tumor environment—an ideal target for immunotherapy.
Zynyz’s Broader Role in Incyte’s Oncology Strategy
Zynyz was initially approved by the FDA in March 2023 for the treatment of metastatic or locally advanced Merkel cell carcinoma, another rare but aggressive skin cancer. The drug is administered intravenously and functions by blocking the PD-1 receptor, thereby reactivating T cells to recognize and destroy cancer cells. Its expansion into SCAC reinforces Incyte’s strategy to build a meaningful presence in the immuno-oncology space, particularly in niche tumor types where unmet needs remain high and competition is relatively low.
In an April 29 investor note following Incyte’s first-quarter earnings report, analysts at Truist highlighted Zynyz as a critical growth driver for the company’s oncology portfolio, alongside Monjuvi, a CD19-directed immunotherapy used in lymphoma. Truist projected that the two drugs could contribute significantly to Incyte’s 2025 oncology revenue forecast of between $415 million and $455 million.
Incyte is not stopping with the U.S. market. The company has also submitted regulatory filings for Zynyz in SCAC to authorities in the European Union and Japan, aiming to broaden its international footprint and capitalize on the momentum generated by the FDA approval.
A Strong Financial Start to 2025
Zynyz’s label expansion comes on the heels of a solid financial quarter for Incyte. In its Q1 2025 earnings report released in late April, the company reported revenues of $1.053 billion—a 20% increase year-over-year and well ahead of the $990 million consensus estimate. This performance was largely driven by Jakafi (ruxolitinib), Incyte’s blockbuster JAK1/JAK2 inhibitor for myelofibrosis and other hematologic conditions, which brought in $709 million in the first quarter alone, beating the analyst estimate of $643 million.
As a result of the strong showing, Incyte raised its full-year guidance for Jakafi revenue from $2.95 billion to $3 billion. However, analysts at William Blair noted that the company’s dependence on Jakafi remains a double-edged sword. While Jakafi continues to perform well in its approved indications, the emergence of competing therapies and the looming expiration of key patents—expected by the end of 2028—pose potential challenges to long-term revenue sustainability.
“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. They cautioned that the loss of exclusivity is an “ongoing concern,” emphasizing the need for Incyte to diversify its pipeline and revenue sources.
The approval of Zynyz for the first-line treatment of SCAC marks a high point for Incyte’s oncology ambitions, demonstrating the company’s ability to deliver meaningful innovation even in the face of previous regulatory hurdles. With strong clinical data, a growing body of real-world experience, and international regulatory efforts underway, Zynyz is well-positioned to become a foundational asset in Incyte’s immuno-oncology pipeline.
For patients facing advanced anal cancer, the approval offers a long-overdue advancement in care—one that provides both new hope and evidence of progress in an area long overshadowed in cancer drug development.
As Incyte continues to expand its reach and redefine its portfolio beyond Jakafi, the success of Zynyz could represent both a commercial win and a turning point in the company’s long-term strategic evolution. The year is still young, but for Incyte, 2025 is already shaping up to be transformative.
