Novartis drug PKC412 receives Breakthrough Therapy designation from FDA for newly-diagnosed FLT3-mutated AML

PKC412 (midostaurin) significantly improved overall survival of adult patients eligible to receive standard induction and consolidation chemotherapy.

The Breakthrough Therapy designation for PKC412 is primarily based upon the positive results from the Phase III RATIFY (CALGB 10603) clinical trial. This study was conducted in partnership with the Alliance for Clinical Trials in Oncology and presented during a plenary session at the 57th American Society of Hematology (ASH) Annual Meeting.

Patients who received PKC412 and standard induction and consolidation chemotherapy experienced a significant improvement in overall survival (OS) (hazard ratio = 0.77, P = 0.0074) compared to those who received standard induction and consolidation chemotherapy alone. The median OS for patients in the PKC412 (midostaurin) treatment group was 74.7 months (95% confidence interval [CI]: 31.7, not attained), versus 25.6 months (95% CI: 18.6, 42.9) for patients in the placebo group. No statistically significant differences were observed in the overall rate of grade 3 or higher hematologic and non-hematologic adverse events in the PKC412 treatment group versus the placebo group. A total of 37 deaths were reported, with no difference in treatment-related deaths observed between groups.

"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, the first potential AML targeted therapy, to patients as quickly as possible."

In the US, about 20,000 people were diagnosed with AML in 2015, the majority of whom were adults. According to the latest research, approximately one-third of AML patients also harbor a FLT3 gene mutation, which is associated with worse outcomes and shorter survival than in those without the mutation. PKC412 (midostaurin) is the first drug targeting FLT3 to demonstrate an overall survival benefit in AML.

Since PKC412 (midostaurin) is investigational at this time and is expected to be submitted for FDA approval, Novartis opened a Global Individual Patient Program (compassionate use program) and a US Expanded Treatment Protocol (ETP) to enable PKC412 (midostaurin) access. Patients 18 years of age and older with newly-diagnosed FLT3-mutated AML and able to receive standard induction and consolidation therapy will be considered.

To help identify patients who may have a FLT3 mutation and potentially benefit from treatment with PKC412 (midostaurin), Novartis is collaborating with Invivoscribe Technologies, Inc. who is leading regulatory submissions for a companion diagnostic.