Prior to the FDA’s approval this month, nirogacestat (Ogsiveo) received the following FDA designations applicable to the treatment of desmoid tumors:
- Breakthrough therapy providing a rapid review.
- Fast track to facilitate rapid development.
- Orphan drug qualifying sponsors for certain incentives.
According to a report published in Targeted Oncology, the FDA’s decision was based in part by results of the DeFi Phase 3 clinical trial (NCT03785964). The developer, SpringWorks, anticipates filing its application for Marketing Authorization with the EMA in early 2024.
About Desmoid Tumors
The tumors are noncancerous and occur mostly in the arms, abdomen, and legs. Nirogacestat has been approved to treat these patients. Desmoid tumors are also termed ‘aggressive fibromatosis’.
Although some desmoid tumors do not require immediate therapy, others progress rapidly and must be treated with either surgery, therapy, radiation, or drugs.
The principal administrator of the DeFi Phase 3 trial reported a reduction in the risk of death or disease progression for patients treated with nirogacestat of an impressive 71% versus placebo.
Professor Bernd Kasper of Mannheim University spoke with Target Oncology and emphasized that the DeFi study is not only the largest study but also the most rigorous study of desmoid tumors. The professor further stated that the DeFi study has proven to be the first conclusive study recorded for a gamma-secretase inhibitor.
About the DiFi Study
Seventy patients were treated with nirogacestat, and 72 patients were treated with placebo. The patients who were treated with placebo registered a mean progression-free survival (PFS) of 15.1 months. Note that there was no Kaplan-Meier median PFS rating for nirogacestat.
Nirogacestat patients showed a higher probability of having been event-free at the one-year mark (85%) than patients with placebo (53%). In addition, at two years, survival rates (event-free) were 76% for patients treated with nirogacestat versus 44% for placebo.
Tumor Shrinkage
Tumors were completely eradicated in seven percent of those treated with nirogacestat, as opposed to none in the placebo group. Patients treated with nirogacestat reported a reduction in pain and an improvement in physical functioning and general well-being. Side effects included fatigue and nausea for some individuals.
One hundred percent of patients in the nirogacestat arm reported adverse events compared to 96% observed in the placebo arm. More severe adverse events were reported in 55% of patients receiving nirogacestat versus 17% of patients in the placebo arm.
Prof. Kasper added that nirogacestat demonstrated substantial improvements in all study endpoints and provided a reasonably maintained safety profile. The aforementioned attributes qualified nirogacestat as a definite candidate for registration.
