Varegacestat Advances Toward FDA Review in Desmoid Tumors

Clinical Summary:

• Based on results from the phase 3 RINGSIDE trial, a New Drug Application for varegacestat has been submitted to the FDA for the treatment of adult patients with desmoid tumors. 
• The phase 3 RINGSIDE trial evaluated varegacestat in 156 patients with progressing desmoid tumors, randomized to receive varegacestat or placebo. 
• Varegacestat significantly improved progression-free survival and response rates, with meaningful tumor shrinkage and improvements in pain outcomes.
• Varegacestat may offer a new oral treatment option for desmoid tumors. The NDA submission reflects strong phase 3 data supporting its clinical benefit.

Based on results from the phase 3 RINGSIDE trial, a New Drug Application for varegacestat, an investigational gamma secretase inhibitor, has been submitted to the US Food and Drug Administration (FDA) for the treatment of adult patients with desmoid tumors. 

In this double-blind, placebo-controlled study, 156 patients 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. Key secondary end points included objective response rate (ORR), tumor volume reduction, pain intensity, and safety. 

At analysis, varegacestat reduced the risk of disease progression or death by 84% (hazard ratio [HR], 0.16; 95% confidence interval [CI], 0.071 to 0.375; P < .0001). The confirmed ORR was 56% in the varegacestat arm and 9% in the placebo arm (P < .0001). Exploratory analysis revealed that median tumor volume reduced by 83% in the varegacestat arm and increased by 11% in the placebo arm. Varegacestat improved both landmark tumor shrinkage and pain intensity compared to placebo.

Varegacestat was generally well tolerated, with a safety profile consistent with the gamma secretase inhibitors. The most common treatment-emergent adverse events included diarrhea (82%), fatigue (44%), rash (43%), nausea (35%), and cough (34%), most of which were grade 1/2.

Updated data from the RINGSIDE trial will be presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois. 

Source: 

Immunome. Immunome announces submission of new drug application to US FDA for varegacestat for the treatment of adults with desmoid tumors. Accessed on: April 30, 2026. https://investors.immunome.com/immunome-announces-submission-of-new-drug-application-to-u-s-fda-for-varegacestat-for-the-treatment-of-adults-with-desmoid-tumors/