Rydapt

Rydapt (midostaurin) is an orphan medicinal product designated for acute myeloid leukaemia (29 July 2004) and mastocytosis (4 August 2010). The recommended starting dose for advanced systemic mastocytosis is 100 mg twice daily, while for AML it is 50 mg twice daily. The marketing authorisation application was submitted on 22 July 2016, and a positive opinion for marketing authorisation was issued on 20 July 2017. Rydapt is included in the additional monitoring list and has a shelf-life of 3 years.

In a non-randomised, open-label trial (Study A2213) involving 116 patients across 29 centers in 12 countries, the median duration of study follow-up was 43 months. The Overall Response Rate (ORR) by Valent/Cheson criteria was 46.1%, and by investigator assessment, it was 52.8%. The Overall Response Rate (ORR) by IWG criteria for all patients evaluated was 28.3%. Median overall survival for all patients was 29.9 months, with a 1-year survival probability of 74.1%. For patients with D816 mutated status, median overall survival was 34.3 months, and the 1-year survival probability was 77.9%. In contrast, for D816 wild-type patients, median overall survival was 10.7 months.

Safety findings from the pooled safety dataset indicate that 18% of patients experienced on-treatment deaths, with 5 deaths attributed to cardiac disorders. Grade 3/4 febrile neutropenia occurred in 44% of patients. Other notable adverse events included pneumonia (28.6% in the 100 mg b.i.d. group) and Grade 3-4 nausea (6.0%). Laboratory abnormalities included decreased absolute lymphocyte count (Grade 3/4) in 45.8% of patients, decreased ANC (Grade 3/4) in 26.8%, and hyperglycaemia (Grade 3/4) in 19%. Discontinuation due to disease progression in Study A2213 was 32%.