BOTHELL, Wash. – Immunome, Inc. (Nasdaq: IMNM), a clinical-stage targeted oncology company committed to developing first-in-class and best-in-class targeted cancer therapies, today announced that the European Medicines Agency (EMA) has validated the Marketing Authorization Application (MAA) for varegacestat, an investigational, oral, once-daily gamma secretase inhibitor (GSI), for the treatment of adults with desmoid tumors. Validation confirms that the application is complete, and the EMA will initiate review under the centralized marketing authorization procedure.
“The EMA’s validation of our MAA for varegacestat is an important step in our efforts to bring this treatment to patients with desmoid tumors globally,” said Clay Siegall, Ph.D., President and Chief Executive Officer of Immunome. “The application is supported by the robust efficacy and safety data generated from the Phase 3 RINGSIDE trial. There is a strong need for new treatment options for desmoid tumors, and we look forward to the potential to make varegacestat available to patients living with this challenging disease.”
The MAA is supported by results from the global, randomized, double-blind, placebo-controlled Phase 3 RINGSIDE trial evaluating varegacestat in adults with progressing desmoid tumors. Detailed efficacy and safety data from the study were presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. The trial met its primary endpoint and achieved all key secondary endpoints, with key findings including:
- The registrational trial met its primary endpoint of improving progression-free survival vs. placebo, with a statistically significant and clinically meaningful 84% reduction in the risk of disease progression or death (hazard ratio = 0.16, p<0.0001).
- The trial also met all key secondary endpoints, including achieving an objective response rate of 56% vs. 9% with placebo (p<0.0001), as assessed by blinded independent central review.
- Varegacestat demonstrated statistically significant improvement in worst pain intensity at week 12, with a clinically significant difference observed as early as the first evaluation at week 4.
- In an exploratory analysis, varegacestat showed a median best change in tumor volume of -83% vs. +11% with placebo, as assessed by blinded independent central review.
- Varegacestat was generally well tolerated with a manageable safety profile, consistent with the gamma secretase inhibitor class. The most common adverse events for participants in the treatment arm were diarrhea (82%), fatigue (44%), rash (43%), nausea (35%) and cough (34%). Most (95%) events were grade 1 or 2.
MAA validation follows acceptance by the U.S. Food and Drug Administration (FDA) of the New Drug Application (NDA) for varegacestat for the treatment of adults with desmoid tumors. The FDA assigned a Prescription Drug User Fee Act (PDUFA) target action date of April 28, 2027.
About the RINGSIDE Trial
The global, randomized, double-blind, placebo-controlled Phase 3 RINGSIDE trial (ClinicalTrials.gov Identifier: NCT04871282) evaluated the efficacy and safety of varegacestat in patients with progressing desmoid tumors. A total of 156 patients were randomized to receive varegacestat 1.2 mg daily or placebo until disease progression or death, representing the largest randomized study in this population. The primary endpoint of the trial was progression-free survival as assessed by blinded independent central review. Statistically controlled key secondary endpoints were confirmed ORR using RECIST v1.1 and change in tumor volume at week 24, both determined by blinded independent central review, as well as change in pain intensity at week 12 as determined using a patient-reported outcome instrument. Additional secondary endpoints included duration of response, best reduction in tumor volume, patient-reported outcomes, and safety and tolerability. RINGSIDE includes an open-label extension phase, which is ongoing.
