The recent first (double) global approval of midostaurin has been reviewed in detail in the First Global Approval report in Adis journal Drugs, based on the development milestones tracked in AdisInsight.

In April 2017, midostaurin (Rydapt®), developed by Novartis Pharmaceuticals, received its first global approval in the US for two indications: One was for newly diagnosed acute myeloid leukemia (AML) that is FLT3 mutation positive as detected by an FDA-approved test, in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation; the FLT3 mutation is tested for using an FDA-approved companion diagnostic. The other for advanced systemic mastocytosis (SM) comprising aggressive SM (ASM), SM with associated haematological neoplasm (SM-AHN), or mast cell leukemia (MCL).[1]

Midostaurin is an orally administered and inhibits a number of multiple receptor tyrosine kinases (TK) including the FLT3 receptor TK, which is mutated in about 30% of patients with AML. In patients with advanced SM, more than 80% of patients have a D816 KIT mutation, this triggers the abnormal proliferation of Mast cells; midostaurin inhibits KIT signalling. Respectively, FLT3 and KIT are key drivers of AML and SM.[2]

The American Cancer Society estimates that in 2017 there will be more than 21,000 new cases of AML. Most will be in adults and approximately half will be fatal.[3] SM is an ultra-rare condition with a prevalence rate of 1-9 per 100,000[4]; the aggressive form is even more rare (1-9 per 1,000,000).[5]

Midostaurin was granted Orphan Drug designation and Priority Review for both AML and SM as well as Breakthrough Therapy designation for AML and, according to Novartis, Global filings are currently underway for the agent in AML and SM.[2]

Bruno Strigini, CEO, Novartis Oncology said that midostaurin “represents a remarkable advance as the first and only targeted therapy approved for patients who had limited options for many years.”[2]

“The overall survival advantage for midostaurin plus chemotherapy seen in the RATIFY trial was a significant advancement for newly diagnosed AML patients with the FLT3 mutation,” said Dr. Richard Stone, Chief of Staff and Director of the Adult Leukemia program at Dana-Farber Cancer Institute, and Alliance for Clinical Trials in Oncology study chair for the RATIFY trial. He further commented that “a new standard of care in this high-risk patient population,” could be established with the availability of midostaurin.[2]

For further information related to the first approval of midostaurin please visit Drugs or to learn more about the overall development of midostaurin across all indications visit AdisInsight.

Image credit: By Lance Cpl. Cory D. Polom –, Public Domain,

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