May 25, 2022, Boston
Servier announced that the U.S. Food and Drug Administration (FDA) has approved ivonidenib in combination with azacitidine for the treatment of adult patients aged 75 years and older or with comorbidities who are ineligible for intensive induction chemotherapy.
Ivosidenib is the first cancer metabolism-targeted therapy approved in combination with azacitidine for the treatment of newly diagnosed IDH1-mutant AML. The AGILE trial is the only Phase III trial specifically designed for newly diagnosed IDH1-mutant AML patients who are ineligible for intensive chemotherapy.
Ivosidenib's supplemental New Drug Application (sNDA) received Priority Review designation and is under review through the FDA's Real-Time Oncology Review (RTOR) pilot program, which aims to ensure patients receive safe and effective treatment as early as possible.
David K. Lee, CEO of Servier Pharmaceuticals, stated, "This approval further strengthens the clinical evidence base for Ivosidenib in multiple IDH1-mutant cancer types. As pioneers in the science of targeting IDH inhibition in oncology, we are proud to provide a new treatment option for the acute myeloid leukemia population and will continue to push the boundaries of innovation in oncology and other medical fields."
This expanded indication approval for Ivosidenib is based on data from the AGILE study.
Expert Review
Dr. Eytan M. Stein, Director of the Leukemia Drug Development Program at Memorial Sloan Kettering Cancer Center, stated: "AML is a rapidly progressing, difficult-to-treat, and poorly prognostic blood cancer. Ivosidenib in combination with azacitidine not only demonstrates a good safety profile but is also the first therapy to significantly improve event-free survival and overall survival in cancer metabolic targeted therapy, highlighting its significant value as a novel combination regimen for newly diagnosed IDH1-mutant AML patients who are ineligible for intensive chemotherapy."
Side Effects
The safety profile of Ivosidenib in combination with azacitidine is consistent with previous data: Common adverse reactions (≥10%): nausea, vomiting, QT interval prolongation, insomnia, differentiation syndrome, leukocytosis, hematoma, hypertension, arthralgia, dyspnea, headache.
Laboratory abnormalities (≥10%): leukopenia, thrombocytopenia, decreased hemoglobin, neutropenia, lymphocytosis, elevated blood glucose, decreased serum phosphorus, elevated AST, decreased serum magnesium, elevated alkaline phosphatase, elevated serum potassium.
Recommended dosage
500 mg orally once daily.
Other indications
Ivosidenib is also approved as monotherapy in the United States for:
1. Adult patients with relapsed/refractory IDH1-mutant AML.
2. Newly diagnosed adult patients with IDH1-mutant AML aged ≥75 years or with comorbidities who cannot receive intensive chemotherapy.
3. Patients with previously treated IDH1-mutant cholangiocarcinoma (first approved for non-hematologic malignancies).
