STAMFORD, Conn. — SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, announced today that the European Medicines Agency (EMA) has validated the Marketing Authorization Application (MAA) 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 (EU) for the treatment of desmoid tumors. Nirogacestat previously received Orphan Drug designation from the European Commission for the treatment of soft tissue sarcoma.
“The validation of our marketing authorization application is an important step towards bringing nirogacestat to patients with desmoid tumors in the European Union who currently do not have an approved therapy,” said Saqib Islam, Chief Executive Officer of SpringWorks. “We look forward to working with the EMA on this important submission.”
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 (PFS), demonstrating a statistically significant improvement over placebo with a 71% reduction in the risk of disease progression (hazard ratio (HR) = 0.29 (95% CI: 0.15, 0.55); p< 0.001). Median PFS was not reached in the nirogacestat arm and was 15.1 months in the placebo arm. Confirmed objective response rate (ORR) based on blinded independent central review of Response Evaluation Criteria in Solid Tumors v1.1 was 41% with nirogacestat versus 8% with placebo (p<0.001); 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 (PROs) measured as of the cycle 10 assessment, including pain (p<0.001), desmoid tumor-specific symptoms (p<0.001), physical/role functioning (p<0.001), and overall health-related quality of life (p≤0.01). Nirogacestat exhibited a manageable safety and tolerability profile. The most common adverse events (>15%) 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.
“Desmoid tumors can have a significant impact on patients’ lives and there is a pressing need for a new treatment for patients in Europe,” said Bernd Kasper, M.D., Ph.D., University of Heidelberg, Mannheim Cancer Center, Mannheim, Germany and Principal Investigator of the DeFi trial. “In the DeFi trial, nirogacestat demonstrated significant improvements across progression-free survival, objective response rate, and patient-reported outcomes, and had a safety profile that supports long-term dosing. These results support that nirogacestat will be a practice-changing therapy if approved by the EMA.”
In November 2023, the U.S. Food and Drug Administration approved OGSIVEO™ (nirogacestat) for the treatment of adults with progressing desmoid tumors who require systemic treatment. The U.S. prescribing information includes the following Warnings & Precautions: diarrhea, ovarian toxicity, hepatotoxicity, non-melanoma skin cancers, electrolyte abnormalities, and embryo-fetal toxicity.
About Desmoid Tumors
Desmoid tumors (sometimes referred to as aggressive fibromatosis, or desmoid fibromatosis) 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.
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. In the European Union, the incidence of desmoid tumors is estimated to be approximately 3-5 cases per million per year.
Although they do not metastasize, desmoid tumors are associated with recurrence rates of up to 77% after surgical resection. Desmoid tumor experts and treatment guidelines now recommend systemic therapies as first-line intervention instead of surgery for most tumor locations requiring treatment.
About OGSIVEO™ (nirogacestat)
OGSIVEO (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.
OGSIVEO 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.
SpringWorks is also evaluating nirogacestat as a potential treatment for patients with ovarian granulosa cell tumors and for patients with multiple myeloma as part of several B-cell maturation agent (BCMA) combination therapy regimens in collaboration with leaders in industry and academia.
About SpringWorks Therapeutics
SpringWorks is a commercial-stage biopharmaceutical company applying a precision medicine approach to developing and delivering life-changing medicines for people with severe rare diseases and cancer. OGSIVEO™ (nirogacestat), approved in the United States for the treatment of adult patients with progressing desmoid tumors who require systemic treatment, is the Company’s first FDA-approved therapy. SpringWorks also has a diversified targeted therapy pipeline spanning solid tumors and hematological cancers, with programs ranging from preclinical development through advanced clinical trials. In addition to its wholly owned programs, SpringWorks has also entered into multiple collaborations with innovators in industry and academia to unlock the full potential for its portfolio and create more solutions for patients in need.
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