EU approval: First active ingredient for desmoid tumors

Desmoid tumors are rare, locally aggressive, benign tumors that develop in the connective tissue of the body. An estimated 1,300 to 2,300 new cases are diagnosed in the EU each year. The peak incidence is between 20 and 44 years of age, and Women are two to three times more likely to be affected than men, according to a virtual press conference by Springworks Therapeutics, a biopharmaceutical company owned by Merck KGaA. Desmoid tumors can cause severe Pain , functional limitations, restricted mobility, disfigurement, and severe, persistent fatigue are difficult to treat. Their unpredictable nature and high recurrence rate, which can significantly impact the quality of life of those affected, make them difficult to treat.

Nirogacestat was approved in the EU on August 18. Market launch in Germany is expected to begin in the fourth quarter of 2025. The active ingredient may be used as monotherapy for the treatment of adult patients with progressive desmoid tumors requiring systemic treatment. The recommended oral dose is 150 mg Ogsiveo twice daily.

Nirogacestat is a reversible and non-competitive γ-secretase inhibitor that blocks the proteolytic activation of the Notch receptor. The Notch signaling pathway plays an important role in tumor development and growth. γ-secretase inhibitors were originally considered potential treatments for Alzheimer's disease. Only later was their potential benefit in desmoid tumors discovered and further investigated.

The EU approval of Ogsiveo is based on data from the Phase III DeFi study, which enrolled 142 adult patients with progressive desmoid tumors. The study met its primary endpoint of improved progression-free survival. Nirogacestat achieved a statistically significant improvement compared to placebo: the risk of disease progression was reduced by 71 percent. Furthermore, treatment with the new drug led to a significant improvement in the objective response rate (41 percent versus 8 percent). Complete remissions occurred in 7 percent of patients and were absent with placebo. Furthermore, nirogacestat achieved early and sustained improvement in patient-reported endpoints, including pain and overall health-related quality of life.

The most commonly observed side effects are diarrhea, rash, ovarian toxicity in women of childbearing age, nausea, fatigue, hypophosphatemia, headache and stomatitis.