On July 20, 2018, the FDA approved ivosidenib (Tibsovo; Agios Pharmaceuticals), a first-in-class inhibitor of isocitrate dehydrogenase-1 (IDH1), for the treatment of adults with relapsed or refractory acute myeloid leukemia (AML) and a susceptible IDH1 mutation, as detected by the FDA-approved test.
On the same day, the FDA approved the RealTime IDH1 test, a companion diagnostic to ivosidenib for the detection of IDH1 mutation.
“Tibsovo 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. “The use of Tibsovo is associated with a complete remission in some patients and a reduction in the need for both red cell and platelet transfusions.”
The FDA approved ivosidenib using its priority review and fast track, and granted it an orphan drug designation for this indication.
This approval was based on an open-label, single-arm, multicenter clinical trial of 174 adults with relapsed or refractory AML and a confirmed IDH1 mutation. Ivosidenib 500 mg daily was used until disease progression, unacceptable toxicity, or hematopoietic stem-cell transplantation. The median treatment duration was 4.1 months. Of the 174 patients, 21 (12%) had a transplant after ivosidenib therapy.
The overall complete remission (CR) and CR with partial hematologic recovery (CRh) rates were 24.7% and 8.0%, respectively, and the rate of CR+CRh was 32.8%. The median time to response was 2 months, and the median response duration was 8.2 months.
The most common (≥20%) adverse reactions reported with ivosidenib were fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema, nausea, mucositis, prolonged QT interval, rash, pyrexia, cough, and constipation.