FDA Approves SpringWorks’ Treatment for Desmoid Tumors
November 28, 2023
Rare Daily Staff
The U.S. Food and Drug Administration approved Springworks Therapeutics’ Ogsiveo as the first approved treatment of adult patients with progressing desmoid tumors who require systemic treatment.
Desmoid tumors are locally aggressive and invasive soft-tissue tumors that can lead to substantial morbidity. In addition, when vital structures are impacted, desmoid tumors can be life-threatening. Although they do not metastasize, desmoid tumors are often refractory to existing off-label systemic therapies and associated with recurrence rates of up to 77 percent following 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.
Ogsiveo is an oral, selective, small molecule gamma secretase inhibitor. The FDA previously granted breakthrough therapy, fast track and orphan drug designations to Ogsiveo for the treatment of desmoid tumors.
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 combination therapy regimens in collaboration with leaders in industry and academia.
The FDA approval of Ogsiveo is based on the results from the phase 3 DeFi trial, which were published in the New England Journal of Medicine. Ogsiveo met the primary endpoint of improving progression-free survival (PFS), demonstrating a statistically significant improvement over placebo with a 71 percent reduction in the risk of disease progression. Median PFS was not reached in the Ogsiveo arm and was 15.1 months in the placebo arm.
The confirmed objective response rate (ORR) based on RECIST v1.1 was 41 percent with Ogsiveo versus 8 percent with placebo. The complete response rate was 7 percent in the Ogsiveo arm and none in the placebo arm.
The median time to first response was 5.6 months with Ogsiveo and 11.1 months with placebo. PFS and ORR improvements were in favor of Ogsiveo regardless of baseline characteristics including sex, tumor location, tumor focality, treatment status, previous treatments, mutational status, and history of familial adenomatous polyposis. Ogsiveo also demonstrated early and sustained improvements in patient-reported outcomes, including pain, desmoid tumor-specific symptoms, physical/role functioning, and overall health-related quality of life.
Ogsiveo exhibited a manageable safety and tolerability profile. The most common adverse events (>15 percent) reported in patients receiving Ogsiveo were diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection, and dyspnea.
“This community has been waiting for an effective treatment that not only shrinks their tumors but also significantly improves pain, which is the most debilitating symptom reported by people living with desmoid tumors,” said Saqib Islam, CEO of SpringWorks. “We are pleased with the broad label, which includes all progressing adult patients and specifically references improvement in pain and believe Ogsiveo has the potential to become the new standard of care for people living with these devastating tumors.”
Photo: Saqib Islam, CEO of SpringWorks Therapeutics
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