Core Insights - SpringWorks Therapeutics announced long-term efficacy and safety data from the Phase 3 DeFi trial of OGSIVEO® (nirogacestat) for treating adults with progressing desmoid tumors, published in the Journal of Clinical Oncology [1][2] - The trial demonstrated that longer-term treatment with OGSIVEO is associated with further reductions in tumor size, increased objective response rates, and sustained improvement in patient-reported outcomes [1][3] Efficacy and Safety Data - The long-term follow-up data showed that the objective response rate (ORR) improved from 34.3% in year 1 to 45.7% for patients treated for up to 4 years, with additional complete and partial responses observed [3] - The median best percent reduction in target tumor size was −32.3% at year one and −75.8% for patients completing at least four years of treatment [3] - Improvements in patient-reported outcomes were noted early and sustained with up to 45 months of treatment [3] Adverse Events - The incidence and severity of treatment-emergent adverse events (TEAEs) decreased over the treatment duration, with common adverse events including diarrhea, ovarian toxicity, and rash [4][19] - Serious adverse reactions occurred in ≥2% of patients, with ovarian toxicity reported in 4% [19] Trial Design and Patient Demographics - The DeFi trial was a global, randomized, multicenter, double-blind, placebo-controlled study involving 142 patients, with a primary endpoint of progression-free survival [5][6] - Desmoid tumors are rare, locally aggressive tumors, primarily affecting individuals aged 20 to 44, with a higher prevalence in females [7] Product Information - OGSIVEO® (nirogacestat) is an oral gamma secretase inhibitor approved for treating adult patients with progressing desmoid tumors requiring systemic treatment [8] - The drug has received Orphan Drug designation from the FDA and EMA for this indication [8]

Core Insights - Nirogacestat is poised to become the first and only approved therapy in the EU for desmoid tumors if the European Commission grants marketing authorization, with a decision expected in Q3 2025 [1][2] Company Overview - SpringWorks Therapeutics, Inc. is a biopharmaceutical company focused on severe rare diseases and cancer, currently advancing nirogacestat for desmoid tumors [2][10] - The company has previously received Orphan Drug designation for nirogacestat from the European Commission [3] Clinical Trial Results - The positive opinion from the EMA's CHMP is based on the Phase 3 DeFi trial, which demonstrated a 71% lower risk of disease progression for nirogacestat compared to placebo [3][6] - The DeFi trial involved 142 patients, with nirogacestat showing significant improvements in progression-free survival, objective response rate, and patient-reported outcomes [6] Safety Profile - Nirogacestat has a manageable safety and tolerability profile, with common adverse reactions including diarrhea, nausea, and fatigue [4] Disease Context - Desmoid tumors are rare, aggressive tumors with an estimated 1,300-2,300 new cases diagnosed annually in the EU, predominantly affecting individuals aged 20 to 44 [7][8] - Despite not metastasizing, desmoid tumors have high recurrence rates, leading to a shift in treatment guidelines recommending systemic therapies as first-line interventions [8]