The Food and Drug Administration (FDA) has accepted for Priority Review the New Drug Application (NDA) for nirogacestat for the treatment of adult patients with desmoid tumors.

Desmoid tumors, also known as aggressive fibromatosis or desmoid-type fibromatosis, are rare, generally nonmalignant, soft tissue tumors that are abnormal growths of connective tissue. Nirogacestat is an oral, selective, small molecule gamma secretase inhibitor that works by blocking proteolytic activation of Notch receptors. 

The NDA is supported by data from the randomized, double-blind, placebo-controlled phase 3 DeFi trial ( Identifier: NCT03785964), which evaluated the efficacy and safety of nirogacestat in adults with desmoid tumors. Patients were randomly assigned 1:1 to receive either nirogacestat 150mg orally twice daily (n=70) or placebo (n=72). The primary endpoint was progression free survival.

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Findings demonstrated that treatment with nirogacestat significantly reduced the risk of disease progression by 71% compared with placebo (hazard ratio, 0.29 [95% CI, 0.15-0.55]; P <.001). The median Kaplan-Meier estimate of PFS was not reached in the nirogacestat arm and was 15.1 months in the placebo arm. 

Confirmed objective response rate was reported to be 41% with nirogacestat vs 8% with placebo (P <.001); complete response rate was 7% in the nirogacestat arm and 0% in the placebo arm. Treatment with nirogacestat also met key secondary endpoints of patient-reported outcomes, including reduced pain (P <.001) and other desmoid tumor-specific symptoms (P <.001), improved physical/role functioning (P <.001) and overall health-related quality of life (P =.007).

The most frequently reported treatment-emergent adverse events with nirogacestat compared with placebo were diarrhea (84% vs 35%), nausea (54% vs 39%), and fatigue (51% vs 36%). Among females of childbearing potential who received nirogacestat, 75% (n=27/36) reported ovarian dysfunction.

“People with desmoid tumors can experience severe pain and other debilitating morbidities, and we are excited by the opportunity to potentially transform the standard of care for these patients,” said Saqib Islam, CEO of SpringWorks. “The acceptance of our NDA for nirogacestat with Priority Review represents a significant milestone in our ambition to provide the first approved therapy for patients with desmoid tumors.”

A Prescription Drug User Fee Act target date of August 27, 2023 has been set for the application. The FDA previously granted Fast Track and Breakthrough Therapy designations to nirogacestat for this indication.


  1. SpringWorks Therapeutics announces FDA acceptance and Priority Review of New Drug Application for nirogacestat for the treatment of adults with desmoid tumors. News release. SpringWorks Therapeutics. Accessed February 27, 2023.
  2. SpringWorks Therapeutics announces data from phase 3 DeFi trial evaluating nirogacestat in adult patients with progressing desmoid tumors at the European Society for Medical Oncology (ESMO) Congress 2022. News release. SpringWorks Therapeutics. September 10, 2022. Accessed February 27, 2023.

This article originally appeared on MPR