The European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending approval of midostaurin for the treatment of adults with newly diagnosed acute myeloid leukaemia (AML) who are FLT3 mutation-positive.

If approved by the European Commission (EC), midostaurin will be indicated in combination with standard daunorubicin and cytarabine induction and high-dose cytarabine consolidation chemotherapy, and for patients in complete response, followed by midostaurin single agent maintenance therapy, for adult patients with newly diagnosed AML who are FLT3 mutation-positive.

Midostaurin was also recommended for approval as monotherapy for the treatment of adult patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated haematological neoplasm (SM-AHN) or mast cell leukaemia.

If approved, midostaurin will be the first targeted treatment available in the European Union (EU) for newly diagnosed FLT3 mutation-positive AML patients and advanced systemic mastocytosis (SM) patients.

The opinion follows the recent US Food and Drug Administration approval of midostaurin for FLT3-mutated AML and advanced SM.

AML is a rare and aggressive cancer of the blood and bone marrow. In the EU, there are over 18,000 estimated new cases of AML each year[3]. Approximately one-third of AML patients will have a FLT3 gene mutation.

FMS-like tyrosine kinase 3 (FLT3) is a type of cell-surface receptor which plays a role in increasing the number of certain blood cells and the FLT3 gene mutation can result in faster disease progression, higher relapse rates and lower rates of survival than other forms of AML.

Advanced SM is a rare blood disorder characterised by uncontrolled growth and accumulation of mast cells - mediators of allergic responses - in one or more organs.

In advanced SM, mast cells accumulate in such high quantities that they begin to cause organ damage.

Median overall survival is currently less than six months for mast cell leukaemia, two years for SM-AHN and 3.5 years for ASM.

The positive opinion is based on the Phase III RATIFY clinical trial, recently published in the New England Journal of Medicine (NEJM), which was conducted in collaboration with the Alliance for Clinical Trials in Oncology and 13 international cooperative groups.

In the trial, newly diagnosed FLT3 mutation-positive patients who received midostaurin plus standard chemotherapy experienced significant improvement in overall survival with a 23% reduction in the risk of death compared with placebo plus standard chemotherapy, with median overall survival of 74.7 months and 25.6 months, respectively (hazard ratio [HR] = 0.77, 95% CI, 0.63, 0.95; one-sided p=0.0078). 

The recommendation in advanced SM is based on two single-arm open-label multicenter trials, including the Phase II study (CPKC412D2201), which was the largest prospective trial ever conducted in this rare disorder.

The efficacy of midostaurin was established using modified Valent criteria, with patients demonstrating an overall response rate, defined as a major or partial response, of 59.6% (95% confidence interval [CI], 48.6, 69.8%).

"Novartis is dedicated to bringing new treatment options to patients with rare diseases, including AML and advanced SM, which have seen limited treatment developments in the past 25 years," said Bruno Strigini, CEO, Novartis Oncology. "We are pleased with the positive recommendation from the CHMP and excited to move a step closer to bringing this much-needed treatment to these patients across Europe."

Source: InventivHealth