FDA Accepts New Drug Application for Varegacestat in Adult Patients With Progressing Desmoid Tumors
Clinical Summary:
- The FDA accepted Immunome's new drug application for varegacestat, an investigational oral, once-daily gamma secretase inhibitor, for adults with progressing desmoid tumors based on findings from the phase 3 RINGSIDE trial.
- In the phase 3 RINGSIDE trial, varegacestat significantly improved progression-free survival, objective response rate, tumor volume reduction, and pain compared with placebo while demonstrating a manageable safety profile. Most adverse events were grade 1 or 2.
- If approved, varegacestat could provide a new oral treatment option for adults with progressing desmoid tumors and further expand systemic treatment options for this rare disease.
The US Food and Drug Administration (FDA) has accepted the new drug application for varegacestat (Immunome) for the treatment of adult patients with progressing desmoid tumors, supporting the investigational oral gamma secretase inhibitor as a potential new treatment option.
This acceptance is supported by findings from the phase 3 RINGSIDE trial. In this double-blind, placebo-controlled trial, 156 patients with progressing desmoid tumors were randomized to receive either 1.2 mg of once daily varegacestat or placebo until disease progression or death. The primary end point was progression-free survival (PFS), as assessed by blinded independent central review.
Varegacestat reduced the risk of disease progression or death by 84% compared with placebo (hazard ratio [HR], 0.16; P < .0001). The trial also met all key secondary end points. The ORR was 56% in the varegacestat compared 9% in the placebo arm (P < .0001). Patients receiving varegacestat experienced significant improvement in worst pain intensity at week 12, with clinically meaningful differences observed as early as week 4. In an exploratory analysis, the median best change in tumor volume was –83% in the varegacestat arm compared with +11% in the placebo arm.
Varegacestat was generally well tolerated, with a safety profile consistent with the gamma secretase inhibitor class. The most frequently reported adverse events included diarrhea (82%), fatigue (44%), rash (43%), nausea (35%), and cough (34%). Most adverse events (95%) were grade 1/2.
“We believe varegacestat has the potential to provide an important oral treatment option, supported by robust clinical data across all key efficacy end points. We look forward to working closely with the FDA throughout the review,” stated Clay Siegall, PhD, president and chief executive officer of Immunome.
The agency assigned a Prescription Drug User Fee Act (PDUFA) target action date of April 28, 2027.
Source:
Immunome, Inc. Immunome announces US FDA acceptance of new drug application for varegacestat for the treatment of adults with desmoid tumors. Accessed July 9, 2026. https://www.businesswire.com/news/home/20260708283482/en/Immunome-Announces-U.S.-FDA-Acceptance-of-New-Drug-Application-for-Varegacestat-for-the-Treatment-of-Adults-with-Desmoid-Tumors
