European Commission Approves Midostaurin for AML and Systemic Mastocytosis

The European Commission approved midostaurin (an oral, multitargeted protein kinase inhibitor) for two indications:

  • in combination with standard daunorubicin and standard cytarabine induction therapy or high-dose cytarabine consolidation chemotherapy for patients with newly diagnosed, FLT3-mutated acute myeloid leukemia (AML)
  • as monotherapy for patients with aggressive systemic mastocytosis, systemic mastocytosis with associated hematologic neoplasm, or mast cell leukemia

The approval follows a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use. In AML, the decision was based on data from the phase III RATIFY trial, in which patients with newly diagnosed AML who were treated with midostaurin had a 23 percent lower risk of death (P value not provided) than patients who received a placebo. Midostaurin treatment also extended patients’ median overall survival (74.7 months vs. 25.6 months; hazard ratio = 0.77 [95% CI 0.63-0.95]; p=0.0078). The most common adverse events (AEs; occurring in ≥30% of patients) associated with midostaurin included febrile neutropenia, nausea, exfoliative dermatitis, vomiting, headache, petechiae, and pyrexia.

The recommendation for advanced systemic mastocytosis was based on two single-arm, open-label studies in which midostaurin-treated patients had an overall response rate of 59.6 percent (95% CI 48.6-69.8). The most common AEs associated with midostaurin in the mastocytosis studies were nausea, vomiting, diarrhea, peripheral edema, and fatigue.

On April 28, 2017, the U.S. Food and Drug Administration approved midostaurin for FLT3-mutated AML and advanced systemic mastocytosis.

Sources: Reuters, September 20, 2017; Novartis press release, September 20, 2017.