FLT3,   General AML

Midostaurin multikinase inhibitor receives FDA priority review for FLT3-mutated AML

The multikinase inhibitor midostaurin (PKC412) is the first targeted therapy to improve Overall Survival (OS) in patients with Acute Myeloid Leukemia (AML) and the FMS-like Tyrosine Kinase-3 (FLT3) mutation. This is of significance since the tyrosine kinase receptor FLT3 plays an important role in the survival and proliferation of blasts and approximately 30% of patients with AML carry the FLT3 mutation.

This year this investigational drug received Breakthrough Therapy Designation (BTD) for treatment of newly diagnosed AML patients with FLT3 mutation.

The BTD is primarily based on the positive results from the phase 3 RATIFY (CALGB 10603) trial, presented at the American Society of Hematology (ASH) meeting in 2015.1

The study was conducted by the Alliance for Clinical Trials in Oncology. The key results demonstrated that median OS was 74.7 months for the group receiving midostaurin versus 26 months for the placebo group (P = .007).

This week, this novel agent was placed onto the FDA priority review. The FDA Priority Review Program is in place to expedite the approval of therapeutically important drugs. Through the program, these drugs are given priority in the FDA’s queue of new drugs and are reviewed within 6 months. Midostaurin is currently being evaluated for newly diagnosed FLT3-mutated AML. This represents a great advancement for AML treatment, since patients with AML associated with a FLT3 mutation have a poorer prognosis that is attributed to a higher relapse rate.

Bruno Strigini, the head of Oncology at Novartis (the manufacturers of midostaurin) made the following statement:

"This regulatory designation signifies the importance of midostaurin as a potential therapy for these patients who haven't had the benefit of targeted medicines."

  1. Stone R.M. et al. The Multi-Kinase Inhibitor Midostaurin (M) Prolongs Survival Compared with Placebo (P) in Combination with Daunorubicin (D)/Cytarabine (C) Induction (ind), High-dose C Consolidation (consol), and As Maintenance (maint) Therapy in Newly Diagnosed Acute Myeloid Leukemia (AML) Patients (pts) Age 18-60 with FLT3 Mutations (muts): An International Prospective Randomized (rand) P-Controlled Double-Blind Trial (CALGB 10603/RATIFY [Alliance]). 2015; Oral abstract #6: 57th Annual Meeting of the American Society of Hematology, Orlando, FL.
  2. Drug Dangers. FDA Priority Review Program. http://www.drugdangers.com/fda/priority-review-program.htm. [Accessed November 2016].
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