July 20, 2018
On July 20, 2018, the Food and Drug Administration approved ivosidenib (Tibsovo, Agios Pharmaceuticals, Inc.) for adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible IDH1 mutation as detected by an FDA-approved test.
Approval was based on an open-label, single-arm, multicenter clinical trial (AG120-C-001, NCT02074839) that included 174 adult patients with relapsed or refractory AML with an IDH1 mutation confirmed using the Abbott RealTime IDH1 Assay, the FDA-approved test for selection of patients with AML for treatment with ivosidenib. Ivosidenib was given orally at a starting dose of 500 mg daily until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation. The median treatment duration was 4.1 months (range, 0.1 to 39.5 months). Twenty-one of the 174 patients (12%) received a stem cell transplant following ivosidenib treatment.
Efficacy was established on the basis of the rate of complete remission (CR) plus complete remission with partial hematologic recovery (CRh), CR+CRh duration, and the rate of conversion from transfusion dependence to independence. The CR+CRh rate was 32.8% (95% CI: 25.8%-40.3%). The median time-to-response was 2 months (range, 0.9-5.6 months), and the median response duration was 8.2 months (95% CI: 5.6 -12 months). The CR and CRh rates were 24.7% (95% CI: 18.5%, 31.8%) and 8.0% (95% CI: 4.5%, 13.1%), respectively.
Among the 110 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 41 (37.3%) became independent of RBC and platelet transfusions during any 56-day post-baseline period. Of the 64 patients who were independent of both RBC and platelet transfusions at baseline, 38 (59.4%) remained transfusion independent during any 56-day post-baseline period.
The most common adverse reactions (≥20%) were fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema, nausea, mucositis, electrocardiogram QT prolonged, rash, pyrexia, cough, and constipation.
The FDA today also approved the Abbott RealTime IDH1 Assay for use in selecting patients for treatment with ivosidenib.
The recommended ivosidenib dose is 500 mg orally once daily with or without food until disease progression or unacceptable toxicity. For patients without disease progression or unacceptable toxicity, treatment is recommended for a minimum of 6 months to allow time for clinical response.
FDA granted this application priority review, fast track, and orphan product designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).