FDA Approves Ivosidenib for IDH1-Mutated AML
Today, the U.S. Food and Drug Administration (FDA) approved ivosidenib (Tibsovo) tablets for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) who have a specific genetic mutation. This is the first drug in its class (isocitrate dehydrogenase-1 [IDH1] inhibitors) and is approved for use with an FDA-approved companion diagnostic used to detect specific mutations in the IDH1 gene in patients with AML.
“Ivosidenib is a targeted therapy that fills an unmet need for patients with relapsed or refractory AML who have an IDH1 mutation,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence and Acting Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “The use of ivosidenib is associated with a complete remission in some patients and a reduction in the need for both red cell and platelet transfusions.”
Ivosidenib is an IDH1 inhibitor that works by decreasing abnormal production of the oncometabolite 2-hydroxyglutarate (2-HG), leading to differentiation of malignant cells. If the IDH1 mutation is detected in blood or bone marrow samples using an FDA-approved test, the patient may be eligible for treatment with ivosidenib. Today, the FDA also approved the RealTime IDH1 Assay, a companion diagnostic that can be used to detect this mutation.
Trial Results
The efficacy of ivosidenib was studied in a single-arm trial of 174 adult patients with relapsed or refractory AML with an IDH1 mutation. The trial measured the percentage of patients with no evidence of disease and full recovery of blood counts after treatment (complete remission [CR]), as well as patients with no evidence of disease and partial recovery of blood counts after treatment (complete remission with partial hematologic recovery [CRh]).
With a median follow-up of 8.3 months, 32.8% of patients experienced a CR orCRh that lasted a median 8.2 months. Of the 110 patients who required transfusions of blood or platelets due to AML at the start of the study, 37% went at least 56 days without requiring a transfusion after treatment with ivosidenib.
Common side effects of ivosidenib include fatigue, increase in white blood cells, joint pain, diarrhea, shortness of breath, swelling in the arms or legs, nausea, pain or sores in the mouth or throat, irregular heartbeat (QT prolongation), rash, fever, cough, and constipation.
Ivosidenib must be dispensed with a patient Medication Guide that describes important information about the drug’s uses and risks. The prescribing information for ivosidenib includes a boxed warning that an adverse reaction known as differentiation syndrome can occur and can be fatal if not treated. Signs and symptoms of differentiation syndrome may include fever, dyspnea, acute respiratory distress, radiographic pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain, peripheral edema, or hepatic/kidney/multi-organ dysfunction. At first suspicion of symptoms, doctors should treat patients with corticosteroids and monitor patients closely until symptoms go away.
Other serious warnings include a QT prolongation, which can be life-threatening. Electrical activity of the heart should be tested with an electrocardiogram during treatment. Guillain-Barré syndrome, a rare neurological disorder in which the body's immune system mistakenly attacks part of its peripheral nervous system, has happened in people treated with ivosidenib, so patients should be monitored for nervous system problems.
The FDA granted the approval of ivosidenib to Agios Pharmaceuticals, Inc. The FDA granted the approval of the RealTime IDH1 Assay to Abbott Laboratories.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
