Nirogacestat — Drug Monograph

Brand names: Ogsiveo

Drug class: Other

Mechanism of Action

Oral small-molecule gamma-secretase inhibitor. Gamma-secretase cleaves the Notch receptor to release the Notch intracellular domain, driving Notch-pathway transcription. Desmoid tumors depend on aberrant Wnt/β-catenin and Notch signaling; by blocking Notch activation, nirogacestat suppresses the proliferation of these locally aggressive fibroblastic tumors.

FDA Indications

• Adult patients with progressing desmoid tumors who require systemic treatment (FDA approved 2023)

Common Side Effects

• Diarrhea
• Nausea
• Fatigue
• Hypophosphatemia
• Maculopapular rash
• Stomatitis
• Headache
• Abdominal pain
• Alopecia
• Upper respiratory tract infection

Clinical Pearl

Nirogacestat (DeFi) is the first FDA-approved therapy for desmoid tumors, meaningfully improving progression-free survival and pain. Ovarian dysfunction is a distinctive toxicity in premenopausal women — counsel on fertility implications up front, though it is often reversible after stopping.

Related Therapies & Mechanisms

• Eribulin (Halaven) — Other · Sarcoma
• Tazemetostat (Tazverik) — Other · Sarcoma
• Adagrasib (Krazati) — Other
• Arsenic Trioxide (Trisenox) — Other