Novartis on Friday said that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending approval of Rydapt (midostaurin) for the treatment of adults with newly diagnosed acute myeloid leukemia (AML) who are FLT3 mutation-positive.
If approved by the European Commission (EC), Novartis says that Rydapt 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 Rydapt single agent maintenance therapy, for adult patients with newly diagnosed AML who are FLT3 mutation-positive. Rydapt was also recommended for approval as monotherapy for the treatment of adult patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN) or mast cell leukemia.
If approved, Rydapt 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 (FDA) 2017 approval of Rydapt for FLT3-mutated AML and advanced SM on April 28 and the Swissmedic approval on May 4.
“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.”
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. 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. Prior to the approval of Rydapt in the US, the AML therapeutic strategy had remained relatively unchanged for more than 25 years.
The EC typically adheres to the recommendation of the CHMP and delivers its final decision within approximately two to three months. The decision will be applicable to all 28 EU member states, plus Iceland, Liechtenstein and Norway.
Phase III reactions
In the Phase III AML RATIFY trial, the most frequent adverse reactions (incidence greater than or equal to 30%) in the Rydapt plus standard chemotherapy arm were febrile neutropenia, nausea, exfoliative dermatitis, vomiting, headache, petechiae (small red skin spots) and pyrexia. The most frequent non-hematologic Grade 3/4 adverse reaction was febrile neutropenia.
In advanced SM, the most frequent adverse reactions were nausea, vomiting, diarrhea, peripheral edema and fatigue. The most frequent Grade 3/4 adverse reactions were fatigue, sepsis, pneumonia, febrile neutropenia and diarrhea