FDA Approval Summary: Olutasidenib for Adult Patients with Relapsed or Refractory Acute Myeloid Leukemia with an Isocitrate Dehydrogenase-1 Mutation

On December 1, 2022, the FDA approved the new molecular entity olutasidenib (Rezlidhia, Rigel Pharmaceuticals), a small-molecule inhibitor of isocitrate dehydrogenase 1, for the treatment of adult patients with relapsed or refractory acute myeloid leukemia with a susceptible isocitrate dehydrogenase 1 mutation as detected by an FDA-approved test. The efficacy of olutasidenib was established based on complete remission (CR) + CR with partial hematologic recovery (CRh) rate, duration of CR + CRh, and conversion of transfusion dependence to transfusion independence in Study 2102-HEM-101. In the pivotal trial, 147 adult patients treated with 150 mg twice daily of olutasidenib were evaluable for efficacy. With a median follow-up of 10.2 months, the CR/CRh rate was 35% (95% confidence interval, 27%-43%), with a median duration of response of 25.9 months [95% confidence interval, 13.5-not reached]. Of the 86 patients who were transfusion dependent at baseline, 29 became transfusion independent (34%). The most common (≥20%) adverse reactions were nausea, fatigue, arthralgia, leukocytosis, dyspnea, pyrexia, rash, mucositis, diarrhea, and transaminitis. An assessment of long-term safety of olutasidenib is a condition of this approval.