Bothell, Washington — October 30, 2026
Immunome, Inc. announced that the European Medicines Agency (EMA) has validated its Marketing Authorization Application (MAA) for varegacestat, an investigational oral, once-daily gamma secretase inhibitor (GSI) being developed for adults with desmoid tumors. Validation confirms that the application is complete and allows the EMA to begin its review under the centralized marketing authorization procedure. The submission is supported by positive results from the global, randomized, double-blind, placebo-controlled Phase 3 RINGSIDE trial, which demonstrated statistically significant improvements in the primary endpoint of progression-free survival and all key secondary endpoints. The study reported an 84% reduction in the risk of disease progression or death compared with placebo (hazard ratio 0.16; p<0.0001), alongside an objective response rate of 56% versus 9% with placebo. Varegacestat also demonstrated statistically significant improvements in patient-reported pain intensity. The EMA validation follows the U.S. Food and Drug Administration’s acceptance of Immunome’s New Drug Application (NDA) for the same indication, with a PDUFA target action date of April 28, 2027. If approved in the European Union, varegacestat could become a new oral treatment option for adults living with this chronic and potentially debilitating condition. The company emphasized that the application is supported by the efficacy and safety findings generated in RINGSIDE, while regulatory review remains ongoing.
Phase 3 RINGSIDE Demonstrated Improvements in Disease Control
The RINGSIDE trial (NCT04871282) enrolled 156 adults with progressing desmoid tumors, making it the largest randomized study conducted in this patient population, according to Immunome. Participants were randomized to receive varegacestat 1.2 mg once daily or placebo until disease progression or death. The primary endpoint was progression-free survival assessed by blinded independent central review. Varegacestat achieved a statistically significant improvement, corresponding to an 84% reduction in the risk of disease progression or death compared with placebo (hazard ratio 0.16; p<0.0001). The trial also met all key secondary endpoints, including confirmed objective response rate, tumor-volume change and pain intensity. The objective response rate was 56% with varegacestat compared with 9% with placebo (p<0.0001), based on blinded independent central review. The treatment also produced a statistically significant improvement in worst pain intensity at Week 12, with a clinically significant difference reported as early as the first assessment at Week 4. In an exploratory analysis, median best change in tumor volume was -83% with varegacestat versus +11% with placebo. The tumor-volume result was exploratory and should be distinguished from the trial’s prespecified key secondary endpoint assessing change in tumor volume at Week 24. Detailed study findings were presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. The trial also includes an ongoing open-label extension phase.
Safety Profile and Regulatory Review
Immunome reported that varegacestat was generally well tolerated, with a manageable safety profile consistent with the gamma secretase inhibitor class. The most common adverse events in the treatment arm were diarrhea (82%), fatigue (44%), rash (43%), nausea (35%) and cough (34%). The company reported that 95% of adverse events were Grade 1 or Grade 2. These findings will form part of the evidence reviewed by European regulators alongside the efficacy results and other application data. EMA validation indicates that the MAA has met the procedural requirements to begin assessment; it does not represent a marketing approval or establish when a final regulatory decision will be issued. In the United States, the FDA accepted Immunome’s NDA in July 2026 and assigned a PDUFA target action date of April 28, 2027. Immunome President and Chief Executive Officer Clay Siegall, Ph.D., described the EMA validation as an important step toward potentially making varegacestat available to patients with desmoid tumors globally. The company is pursuing regulatory review in both regions as it advances the candidate toward potential commercialization.
Advertisement
Desmoid Tumors and Immunome’s Oncology Pipeline
Desmoid tumors, also known as aggressive fibromatosis or desmoid-type fibromatosis, are rare, locally aggressive soft-tissue tumors that do not metastasize but can recur and cause substantial morbidity. Patients may experience chronic pain, physical deformity, functional limitations and, in some cases, life-threatening damage to surrounding organs. Although these tumors are not classified as cancerous, progressive disease can require systemic treatment to reduce disease burden and prevent permanent disability. Immunome is developing varegacestat as an oral treatment option for adults with progressing desmoid tumors. Beyond varegacestat, the company’s targeted oncology pipeline includes IM-1021, a clinical-stage ROR1 antibody-drug conjugate (ADC); IM-1617, a clinical-stage solid-tumor ADC; IM-3050, a clinical-stage FAP-targeted radiotherapy candidate; and IM-1340, an IND-cleared solid-tumor ADC. The company is also advancing early-stage ADC programs against undisclosed solid-tumor targets. The EMA’s validation of the varegacestat MAA marks the start of European regulatory assessment, while the U.S. NDA review proceeds toward its assigned target action date. Further regulatory decisions will determine whether the investigational therapy can become available to patients in these markets.
Source:Immunome, Press release
