General Information

Ogsiveo (nirogacestat) is a gamma secretase inhibitor.

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

Dosing/Administration

• Ogsiveo is supplied as tablets for oral administration. 
• The recommended dosage of Ogsiveo is 150 mg administered orally twice daily until disease progression or unacceptable toxicity. Each 150 mg dose of Ogsiveo consists of three 50 mg tablets.
• Ogsiveo may be taken with or without food.
•  Instruct patients to swallow Ogsiveo tablets whole and not to break, crush, or chew prior to swallowing.
• If a patient vomits or misses a dose, instruct the patient to take the next dose at its scheduled time.

Mechanism of Action

Ogsiveo (nirogacestat) is a gamma secretase inhibitor that blocks proteolytic activation of the Notch receptor. When dysregulated, Notch can activate pathways that contribute to tumor growth.

Side Effects

Adverse effects associated with the use of Ogsiveo may include, but are not limited to, the following:

• diarrhea
• ovarian toxicity
• rash
• nausea
• fatigue
• stomatitis
• headache
• abdominal pain
• cough
• alopeca
• upper respiratory tract infection
• dyspnea

Clinical Trial Results

The FDA approval of Ogsiveo was based on results from the Phase 3 DeFi trial. The international, multicenter, randomized, double-blind, placebo-controlled trial enrolled 142 adult patients with progressing desmoid tumors not amenable to surgery. Patients were eligible if the desmoid tumor had progressed within 12 months of screening. Patients were randomized to receive 150 mg Ogsiveo or placebo orally twice daily until disease progression or unacceptable toxicity.

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. Median PFS was not reached in the Ogsiveo arm and was 15.1 months in the placebo arm. Confirmed objective response rate (ORR) based on RECIST v1.1 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 median time to first response was 5.6 months with Ogsiveo and 11.1 months with placebo. PFS and ORR improvements were in favor of Ogsiveo regardless of baseline characteristics including sex, tumor location, tumor focality, treatment status, previous treatments, mutational status, and history of familial adenomatous polyposis. Ogsiveo also demonstrated early and sustained improvements in patient-reported outcomes (PROs), including pain, desmoid tumor-specific symptoms, physical/role functioning and overall health-related quality of life.