Regulatory Decision Summary for Rydapt

The pivotal study for evaluation of efficacy was a multicenter, single-arm phase II study (D2201) in patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL). Rydapt was administered orally at 100 mg twice daily until disease progression or intolerable toxicity. Of the 116 patients enrolled, 84.5% of patients carried the KIT D816V mutation, and 40.5% of patients received prior antineoplastic therapy for SM.

In the primary efficacy population (n = 89), 53 patients achieved a confirmed response during the first 6 cycles of treatment based on modified Valent/Cheson criteria, for an overall response rate (ORR) of 59.6%. The median duration of response was 31.4 months (95% CI: 10.8; NE). Durable responses were also observed when the more stringent criteria from the International Working Group-Myeloproliferative Neoplasms Research and Treatment & European Competence Network on Mastocytosis (IWG-MRT-ECNM) were applied that demonstrated an ORR of 37.4% (95% CI: 28.5, 46.9) in 115 eligible patients, and a duration of response ranging from 2.8 to 60.5 months.

The evaluation of safety was primarily based on integrated analysis of 142 patients who received at least one dose of midostaurin (100 mg twice daily with food) in two single-arm, phase II multicenter studies (D2201 and A2213). Safety findings were consistent with previous clinical studies. The key risks included gastrointestinal disturbances (nausea, vomiting, diarrhea), hematologic toxicity / infections, and cardiac dysfunction. The overall safety profile is considered acceptable in the target population.

Based on the data reviewed, the benefit-risk assessment is considered to be positive for the use of Rydapt in adult patients with ASM, SM-AHN, and MCL, a population with very limited treatment options and a high unmet medical need.