FDA Approves Nirogacestat Tablets for Rare Desmoid Tumors


The approval is the first for a systemic therapy to treat desmoid tumors, offering patients an alternative to surgery.

FDA Approves Nirogacestat Tablets for Rare Desmoid Tumors

The US Food and Drug Administration (FDA) has approved nirogacestat tablets (Ogsiveo) for the treatment of progressing desmoid tumors in adult patients. The indication granted to SpringWorks Therapeutics marks nirogacestat as the first therapy approved to treat adults with the rare, non-cancerous, painful tumors.

Desmoid tumors are a rare subtype of soft tissue sarcomas commonly characterized by impact on structures and organs that which may cause pain, restricted movement, and poorer quality of life. Prior to the FDA approval for nirogacestat, surgical removal has been the primary treatment option—however, the risk of returning tumors or other health challenges are frequent following procedures. It’s for this reason that such systemic therapies have been increasingly assessed for affected patients, according to the FDA.

"The FDA continues to address unmet medical need and advance the development of safe and effective therapies for the millions of Americans whose lives are affected by rare tumors," Richard Pazdur, MD, director of the FDA's Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA's Center for Drug Evaluation and Research, said in a statement. "Desmoid tumors are rare tumors that can lead to severe pain and disability. Today's approval will offer the first approved treatment option for patients beyond surgery and radiation."

Nirogacestat tablet’s benefit for treating desmoid tumors was evidenced by findings from the phase 3, pivotal, randomized, double-blind, placebo-controlled DeFi trial across multiple international centers including 142 adult patients with progressing tumors not amenable to surgery. Patients were randomized 1:1 to either 150 mg nirogacestat or oral placebo, twice daily, and received treatment until observed disease progression or unacceptable toxicity.

Investigators sought a primary efficacy endpoint of progression-free survival (PFS), defined as length of time after treatment initiation in which a person is alive and their tumors do not grow nor spread. Secondary efficacy endpoints including objective response rate, per measured tumor shrinkage.

The team reported a statistically significant improvement in PFS with nirogacestat—a 71% reduced risk of disease progression versus placebo (hazard ratio [HR], 0.29; 95% CI, 0.15 – 0.55; P <.001). Median PFS was 15.1 months in the placebo arm, versus not being reached among treated patients. They additionally observed a significant improvement in objective response rate among patients receiving nirogacestat, in which 41% of treated patients achieved the marker for tumor shrinkage versus just 8% of the placebo arm (P <.001).

Median time to first response was halved among treated patients versus the placebo arm (5.6 months vs 11.1 months); investigators additionally observed early and sustained improvements in patient-reported outcomes including pain, desmoid tumor-specific symptoms, and physical functioning (P <.001).

The most common adverse events to occur in ≥15% of patients in either arm of the trial included diarrhea; ovarian toxicity; rash; nausea; fatigue; stomatitis; headache; abdominal pain; cough; alopecia; upper respiratory tract infection; and dyspnea.

In a statement accompanying the approval, DeFi trial investigator Mrinal M. Gounder, MD, sarcoma medical oncologist at Memorial Sloan Kettering Cancer, praised the clinical breakthrough for patients with the difficult, invasive, and recurring tumor condition.

“OGSIVEO is a highly innovative therapy with efficacy data demonstrating both meaningful antitumor activity and a significant improvement in desmoid tumor symptoms,” Gounder said. “As a treating physician, it was encouraging to see in the DeFi trial that OGSIVEO achieved statistically significant and clinically meaningful improvements across the primary and all key secondary endpoints, while also having a manageable safety profile. This approval represents an important therapeutic advance for patients.”


  1. US Food & Drug Administration. FDA Approves First Therapy for Rare Type of Non-Cancerous Tumors. Press release. Published November 27, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-therapy-rare-type-non-cancerous-tumors
  2. Gounder M, Ratan R, Alcindor T, et al. Nirogacestat, a γ-Secretase Inhibitor for Desmoid Tumors. N Engl J Med. 2023;388(10):898-912. doi:10.1056/NEJMoa2210140
  3. SpringWorks Thereapeutics. SpringWorks Therapeutics Announces FDA Approval of OGSIVEO™ (nirogacestat) as the First and Only Treatment for Adults with Desmoid Tumors. Press release. Published November 27, 2023. https://ir.springworkstx.com/news-releases/news-release-details/springworks-therapeutics-announces-fda-approval-ogsiveotm
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