The U.S. Food and Drug Administration has granted Breakthrough Therapy Designation to midostaurin (PKC412), an investigational treatment for adult patients with newly diagnosed acute myeloid leukemia (AML) who are FLT3 mutation-positive and are eligible to receive standard induction and consolidation chemotherapy.1

This designation is based on positive results from the phase 3 RATIFY trial, which demonstrated a significant improvement in overall survival in patients who received midostaurin compared with those who did not (HR, 0.77; P = .0074).

Median overall survival was 74.7 months (95% CI, 31.7 – not reached) for patients who received standard induction and consolidation chemotherapy plus midostaurin vs 25.6 months (95% CI, 18.6 – 42.9) for patients who received chemotherapy alone.

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In terms of safety, there were no statistically significant differences in the overall rate of grade 3 or higher hematologic and non-hematologic adverse events between the 2 treatment arms. Although a total of 37 deaths were reported, there was no difference in treatment-related deaths between the 2 groups.

For the global study, investigators enrolled a total of 717 previously untreated patients with AML and randomly assigned them to receive chemotherapy plus midostaurin or placebo. Of those, 81% were FLT3 mutation-positive.

Findings from the trial were presented during a plenary session at the American Society of Hematology (ASH) 57th Annual Meeting & Exposition.

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“For more than 25 years, medical developments have been limited for AML patients and the chemotherapy treatment strategy has essentially remained unchanged,” said Alessandro Riva, MD, Global Head, Novartis Oncology Development and Medical Affairs. “We look forward to working closely with the FDA to bring PKC412 (midostaurin), the first potential AML targeted therapy, to patients as quickly as possible.”

Midostaurin is also being studied for the treatment of patients with aggressive systemic mastocytosis/mast cell leukemia.


  1. Novartis drug PKC412 (midostaurin) receives Breakthrough Therapy designation from the FDA for newly-diagnosed FLT3-mutated acute myeloid leukemia (AML) [news release]. East Hanover, NJ: Novartis. February 19, 2016. Accessed February 19, 2016.