FDA Approves First Treatment for Rare Noncancerous Tumors

The FDA has approved Ogsiveo (nirogacestat) tablets for adult patients with progressing desmoid tumors, a rare subtype of soft tissue sarcomas. Although non-cancerous, desmoid tumors can be aggressive and most often occur in the abdomen, arms and legs. The tumors can invade into surrounding structures and organs, resulting in pain and impacting the ability to move. Surgery is standard of care, but tumors often return. About 1,650 new patients are diagnosed annually in the United States.

“Desmoid tumors can have a significant impact on people’s lives and are difficult to manage due to their invasive nature and high rates of recurrence. Ogsiveo is a highly innovative therapy with efficacy data demonstrating both meaningful antitumor activity and a significant improvement in desmoid tumor symptoms,” Mrinal M. Gounder, M.D., sarcoma medical oncologist at Memorial Sloan Kettering Cancer Center (MSK) in New York City and an investigator in the phase 3 DeFi trial, said in a press release.

Developed by SpringWorks Therapeutics, Ogsiveo is an oral, selective, small molecule gamma secretase inhibitor. Gamma secretase cleaves to multiple proteins, which are believed to play a role in pathways that contribute to the growth of desmoid tumors. Ogsiveo is dosed at 150 mg two times daily. It has no boxed warnings and no required Risk Evaluation and Mitigation Strategies (REMS) program. Ogsiveo will be available to order through a specialty pharmacy and specialty distributor network within five to 10 business days. It will have a price of $29,000 for a 30-day supply, company executives said in an investor call. SpringWorks will offer a patient support programs but financial assistance and a copay program, as well as a nurse advocates to support patients.

The FDA approval is based on the results from the phase 3 DeFi trial, which were published in March 2023 in the New England Journal of Medicine. In the trial, Ogsiveo 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. Confirmed objective response rate was 41% with Ogsiveo versus 8% with placebo; the complete response rate was 7% in the Ogsiveo arm and 0% in the placebo arm.

The most common adverse events reported in patients receiving Ogsiveo were diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection, and dyspnea.

SpringWorks is also evaluating nirogacestat as a potential treatment for patients with ovarian granulosa cell tumors and for patients with multiple myeloma.