SpringWorks Therapeutics announces EMA validaion for nirogacestat MAA

SpringWorks Therapeutics announced that the European Medicines Agency has validated the Marketing Authorization Application for nirogacestat, an oral gamma secretase inhibitor, for the treatment of adults with desmoid tumors. If approved, nirogacestat will be the first therapy to receive marketing authorization in the European Union for the treatment of desmoid tumors. Nirogacestat previously received Orphan Drug designation from the European Commission for the treatment of soft tissue sarcoma. The MAA submission is based on results from the Phase 3 DeFi trial. In DeFi, nirogacestat met the primary endpoint of improving progression-free survival, demonstrating a statistically significant improvement over placebo with a 71% reduction in the risk of disease progression. Median PFS was not reached in the nirogacestat arm and was 15.1 months in the placebo arm. Confirmed objective response rate based on blinded independent central review of Response Evaluation Criteria in Solid Tumors v1.1 was 41% with nirogacestat versus 8% with placebo; the complete response rate was 7% in the nirogacestat arm and 0% in the placebo arm. Nirogacestat also demonstrated early and sustained improvements in patient-reported outcomes measured as of the cycle 10 assessment, including pain. desmoid tumor-specific symptoms, physical/role functioning and overall health-related quality of life. Nirogacestat exhibited a manageable safety and tolerability profile. The most common adverse events reported in patients receiving nirogacestat were diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection, and dyspnea. The DeFi trial results were published in the March 9, 2023 edition of the New England Journal of Medicine and presented during a Presidential Symposium at the European Society for Medical Oncology Congress 2022