FDA approved Ogsiveo (nirogacestat) for Progressing Desmoid TumorsFDA approved Ogsiveo, first drug for rare desmoid tumors

Ogsiveo is a gamma secretase inhibitor. The exact mechanism in desmoid tumors is not fully elucidated, but gamma secretase inhibition is thought to reduce Notch signaling, which is implicated in desmoid tumor growth.

Ogsiveo is indicated for adult patients with progressing desmoid tumors who require systemic treatment.

The recommended dosage is 150 mg orally twice daily until disease progression or unacceptable toxicity. Ogsiveo may be taken with or without food. Tablets should be swallowed whole and not broken, crushed, or chewed. If a dose is missed or vomited, the next dose should be taken at its scheduled time. Dose modifications for adverse reactions include withholding and restarting at 100 mg twice daily for certain toxicities, and permanent discontinuation for Grade 3 or 4 ALT/AST elevation.

The safety and efficacy were evaluated in 69 patients in the DeFi trial. Patients received Ogsiveo 150 mg twice daily or placebo. The median duration of exposure was 20.6 months. Serious adverse reactions occurred in 20% of patients. The most common adverse reactions (≥15% with ≥5% difference vs placebo) were diarrhea (84%), ovarian toxicity (75% in females), rash (68%), nausea (54%), fatigue (54%), stomatitis (39%), headache (30%), abdominal pain (22%), cough (20%), alopecia (19%), upper respiratory tract infection (17%), and dyspnea (16%).

Not reported in label.

Ogsiveo is the first FDA-approved systemic therapy specifically for desmoid tumors. It is indicated for patients with progressing disease who require systemic treatment. The approval provides a targeted option for this rare tumor type.