EU CHMP recommends approval of Rydapt (midostaurin) for acute myeloid leukemia (FLT3 mutation-positive)- Novartis

Novartis announced that the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending approval of Rydapt (midostaurin) for the treatment of adults with newly diagnosed acute myeloid leukemia (AML) who are FLT3 mutation-positive. If approved by the European Commission (EC), Rydapt will be indicated in combination with standard daunorubicin and cytarabine induction and high-dose cytarabine consolidation chemotherapy, and for patients in complete response, followed by Rydapt single agent maintenance therapy, for adult patients with newly diagnosed AML who are FLT3 mutation-positive.

Rydapt was also recommended for approval as monotherapy for the treatment of adult patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN) or mast cell leukemia.

The positive opinion is based on the Phase III RATIFY (CALGB 10603 [Alliance]) clinical trial, which was conducted in collaboration with the Alliance for Clinical Trials in Oncology and 13 international cooperative groups. In the trial, newly diagnosed FLT3 mutation-positive patients who received Rydapt plus standard chemotherapy experienced significant improvement in overall survival with a 23% reduction in the risk of death compared with placebo plus standard chemotherapy, with median overall survival of 74.7 months and 25.6 months, respectively. The full data from the RATIFY trial were recently published in the New England Journal of Medicine. The recommendation in advanced SM is based on two single-arm open-label multicenter trials, including the Phase II study (CPKC412D2201), which was the largest prospective trial ever conducted in this rare disorder.

Comment: Novartis is planning a Phase III study in newly diagnosed AML patients without a FLT3 mutation (wildtype).