On June 20, 2025 SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, reported that the European Medicine Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the approval of nirogacestat, an oral gamma secretase inhibitor, as monotherapy for the treatment of adults with progressing desmoid tumors who require systemic treatment (Press release, SpringWorks Therapeutics, JUN 20, 2025, View Source [SID1234654023]). The European Commission (EC) will review the CHMP opinion and is expected to make a final decision regarding the approval in the third quarter of 2025.
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"The positive opinion from the CHMP reflects the meaningful benefits nirogacestat can offer patients in Europe where currently there are no approved treatment options," said Saqib Islam, Chief Executive Officer of SpringWorks. "We look forward to the European Commission’s decision as we strive to bring nirogacestat to desmoid tumor patients globally."
Nirogacestat previously received Orphan Drug designation from the European Commission for the treatment of soft tissue sarcoma. The CHMP opinion was based on the Marketing Authorization Application (MAA) for nirogacestat, which centered on results from the Phase 3 DeFi trial that were published in The New England Journal of Medicine.1 In DeFi, nirogacestat met the primary endpoint of improving progression-free survival (PFS), demonstrating a 71% lower risk of disease progression compared to placebo. Nirogacestat demonstrated a significant improvement in objective response rate as well as early and sustained improvements in patient-reported outcomes (PROs), including pain, physical functioning and overall quality of life.
Nirogacestat exhibited a manageable safety and tolerability profile. The most common adverse reactions reported in patients receiving nirogacestat were diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection, and dyspnea.
"Desmoid tumors can have a profound impact on patients as well as their loved ones, and the positive CHMP opinion underscores the potential benefit of nirogacestat for these patients," Bernd Kasper, M.D., Ph.D., Professor, University of Heidelberg, Mannheim Cancer Center, Mannheim, Germany, and principal investigator of the DeFi trial. "It is very encouraging that a significant number of people taking nirogacestat experienced reductions in their tumor size and also rapid and sustained relief of their desmoid tumor symptoms, including pain."
Nirogacestat is approved in the U.S. for the treatment of adults with progressing desmoid tumors who require systemic treatment.
About the DeFi Trial
DeFi (NCT03785964) was a global, randomized (1:1), multicenter, double-blind, placebo-controlled pivotal Phase 3 trial that evaluated the efficacy, safety and tolerability of nirogacestat in adult patients with progressing desmoid tumors. The double-blind phase of the study randomized 142 patients (nirogacestat, n=70; placebo n=72) to receive 150 mg of nirogacestat or placebo twice daily. Key eligibility criteria included tumor progression by ≥20% as measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) within 12 months prior to screening. The primary endpoint was progression-free survival (PFS), as assessed by blinded independent central review, or death by any cause. Secondary and exploratory endpoints included safety and tolerability measures, objective response rate (ORR), duration of response, changes in tumor volume assessed by magnetic resonance imaging (MRI), and changes in patient-reported outcomes (PROs). DeFi also included an open-label extension phase.
About Desmoid Tumors
Desmoid tumors are rare, aggressive, locally invasive tumors of the soft tissues that can be serious, debilitating, and, in rare cases when vital structures are impacted, life-threatening.2,3
Desmoid tumors are most commonly diagnosed in patients between the ages of 20 and 44 years, with a two-to-three times higher prevalence in females.4,5 It is estimated that there are 1,300-2,300 new desmoid tumor cases diagnosed per year in the European Union.6,7
Although desmoid tumors do not metastasize, they can be associated with recurrence rates of up to 77% after surgical resection.5,8 Desmoid tumor experts and treatment guidelines now recommend systemic therapies as first-line intervention for most tumor locations requiring treatment.9,10
About Nirogacestat
Nirogacestat is an oral, selective, small molecule gamma secretase inhibitor approved in the United States for the treatment of adult patients with progressing desmoid tumors who require systemic treatment. Nirogacestat is not approved for the treatment of any other indication in the United States, or for any indication in any other jurisdiction by any other health authority.