On November 27, 2023, the U.S. Food and Drug Administration (FDA) approved nirogacestat (Ogsiveo™) for use in adult patients with progressing desmoid tumors who require systemic treatment. Nirogacestat is the first approved treatment for desmoid tumors.

FDA update

Efficacy was evaluated in DeFi (NCT03785964), an international, multicenter, randomized, double-blind, placebo-controlled trial involving 142 patients with desmoid tumors that had progressed within 12 months of screening and were not amenable to surgery. Patients were randomized 1:1 to receive either 150 mg nirogacestat or placebo orally twice daily until they experienced disease progression or unacceptable toxicity.

The major efficacy outcome measure was progression-free survival (PFS), based on RECIST v1.1, as assessed by blinded independent central review or on clinical progression assessed by the investigator (and adjudicated by independent review). Median PFS was not reached (NR) in the nirogacestat arm (95% CI = NR, NR) and 15.1 months (95% CI = 8.4, NR) in the placebo arm (HR = 0.29 [95% CI = 0.15, 0.55]; p < 0.001). An exploratory analysis of PFS based only on radiographic progression demonstrated a HR of 0.31 (95% CI = 0.16, 0.62).

Objective response rate was an additional efficacy outcome measure. It was 41% (95% CI = 29.8, 53.8) in the nirogacestat arm and 8% (95% CI = 3.1, 17.3) for placebo (p < 0.001). Efficacy results were supported by change from baseline in patient-reported worst pain favoring the nirogacestat arm.

The most common adverse reactions reported during the clinical trial were diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection, and dyspnea.

The recommended nirogacestat dose is 150 mg (three 50 mg tablets), administered orally twice daily with or without food, until patients experience disease progression or unacceptable toxicity.

View the prescribing information for nirogacestat.

Nirogacestat’s review used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

The drug’s application was granted priority review, breakthrough designation, fast track designation, and orphan drug designation. FDA-expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.

For assistance with single-patient investigational new drug requests for oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or OncProjectFacilitate@fda.hhs.gov.