FDA submissions for PKC 412 (midostaurin) to treat AML patients with a FLT3 mutation and for systemic mastocytosis.- Novartis

Novartis has announced that the FDA granted Priority Review to the PKC 412 (midostaurin) new drug application (NDA) for the treatment of acute myeloid leukemia (AML) in newly-diagnosed adults with an FMS-like tyrosine kinase-3 (FLT3) mutation, as well as for the treatment of advanced systemic mastocytosis (SM). The premarket approval application (PMA) for the PKC 412 (midostaurin) FLT3 companion diagnostic, developed in collaboration with Invivoscribe Technologies, Inc. (IVS) has also been accepted for review by the FDA. Outside the US, the marketing authorization application for PKC 412 (midostaurin) in these indications has already been accepted by the European Medicines Agency (EMA).

The NDA submission for PKC 412 (midostaurin) includes data from the largest clinical trials conducted to date in each indication. In the Phase III RATIFY trial (CALGB 10603), which investigated PKC 412 (midostaurin) plus standard chemotherapy versus placebo plus standard chemotherapy in adult patients less than 60 years of age with FLT3-mutated AML, those in the PKC 412 (midostaurin) arm experienced a statistically significant improvement in overall survival (OS) with a 23% reduction in risk of death compared to the placebo arm (hazard ratio [HR] = 0.77, P = 0.0074)[1]. Based on these data, PKC 412 (midostaurin) was also granted Breakthrough Therapy designation by the FDA earlier this year for newly-diagnosed FLT3-mutated AML.

Comment:Approximately 30% of patients with AML have a genetic mutation within the FLT3 gene. A mutation within the FLT3 gene results in continuous signals to the cancer cells, causing them to grow in an uncontrolled manner, and preventing them from natural death. These patients have a poorer survival than other patients with AML treated with standard therapeutic approaches. PKC 412 is an agent that blocks the growth signal caused by the FLT3 mutation, resulting in cellular death.