European regulators have recommended expanding the approved uses of Zynyz (retifanlimab) to include the treatment of adults with locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC) that cannot be surgically removed. The treatment would be used in combination with the chemotherapy drugs carboplatin and paclitaxel.
This recommendation marks a potential turning point in the treatment of this rare cancer, offering a new option for patients facing limited therapeutic choices. SCAC is the most common type of anal cancer, accounting for approximately 85% of all cases.
Approximately 10,000 people are diagnosed with SCAC each year, and the incidence has been rising by around 3% annually over the past decade. This increase is largely attributed to the spread of high-risk strains of the human papillomavirus (HPV), particularly HPV 16 and 18, which are known to cause several types of cancer. Around 25% of individuals with SCAC experience cancer that spreads to other parts of the body.
When SCAC becomes metastatic, outcomes are significantly worse, with a 5-year survival rate of only 36% according to research. Currently, there are no medications specifically authorized in the European Union for treating adults with SCAC.
For SCAC that hasn’t spread, treatment options are limited to chemotherapy and radiation therapy. However, up to 60% of these patients experience cancer recurrence within five years of initial treatment. Patients with metastatic disease at diagnosis face a particularly poor prognosis, with 5-year survival rates ranging from 15% to 20%. Treatment for metastatic SCAC typically focuses on palliative care, primarily chemotherapy, to manage symptoms and improve quality of life.
The active ingredient in Zynyz, retifanlimab, is a monoclonal antibody. This protein works by blocking the PD-1 receptor found on the surface of immune cells called T cells. Some cancers, including SCAC, produce a protein called PD-L1 that attaches to the PD-1 receptor on T cells, effectively suppressing their activity and preventing them from attacking the cancer. By blocking PD-1, retifanlimab prevents this inactivation, enhancing the immune system’s ability to destroy cancer cells.
The European Medicines Agency’s (EMA) recommendation is based on the results of a randomized, double-blind clinical trial involving 308 adults with locally recurrent or metastatic SCAC that could not be removed surgically. All participants received six cycles of chemotherapy, consisting of carboplatin and paclitaxel. They were also treated with either Zynyz or a placebo every four weeks. The study found that 50% of patients treated with Zynyz in combination with chemotherapy survived for 9.3 months or longer without disease progression, compared to 7.4 months for those receiving placebo plus chemotherapy.
While median overall survival was 32.8 months for those treated with Zynyz compared to 22.2 months for those receiving placebo, these results were not statistically significant, meaning the difference between the two groups could have been due to chance. Despite this uncertainty regarding Zynyz’s impact on overall survival, the EMA concluded that, considering the progression-free survival data, the drug demonstrates a beneficial effect.
The most common adverse reactions reported with Zynyz in combination with carboplatin and paclitaxel were neutropenia (low levels of neutrophils, a type of white blood cell), pruritus (itching), rash, lymphopenia (low levels of lymphocytes, another type of white blood cell), hypothyroidism (underactive thyroid), and elevated levels of the liver enzyme alanine aminotransferase, which can indicate liver problems.
The EMA’s opinion is a step toward making Zynyz accessible to patients. The agency will now forward its recommendation to the European Commission for a decision on extending the therapeutic indication across the EU. Once approved, pricing and reimbursement decisions will be made at the national level in each member state, considering the drug’s potential role within their respective healthcare systems.
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References
Rao S, et al. Retifanlimab with carboplatin and paclitaxel for locally recurrent or metastatic squamous cell carcinoma of the anal canal (POD1UM-303/InterAACT-2): a global, phase 3, randomised, double-blind trial. Lancet. June 14, 2025;405(10495):2144-2152. Doi: 10.1016/S0140-6736(25)00631-2.
Notes
• The applicant for Zynyz is Incyte Biosciences Distribution B.V.
• Zynyz was designated as an orphan medicine for the treatment of anal cancer on October 19, 2020.
• Following this positive CHMP opinion, the Committee for Orphan Medicinal Products (COMP) will assess whether the orphan designation should be maintained.
• The assessment report with the relevant references will be published once the European Commission issues a decision.
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