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

The Food and Drug Administration approved ivosidenib (Tibsovo; Agios, Cambridge, MA), a small molecule inhibitor of isocitrate dehydrogenase (IDH)1 on July 20, 2018, for treatment of adults with relapsed or refractory acute myeloid leukemia (R/R AML) with susceptible IDH1 mutation as detected by an FDA-approved test. The efficacy of ivosidenib was established based on complete remission (CR) + CR with partial hematologic recovery (CRh) rate, duration of CR+CRh, and conversion from transfusion-dependence (TD) to transfusion-independence (TI) in the single-arm Study AG120-C-001. With median follow-up 8.3 months for 174 adults with IDH1-mutated R/R AML treated with 500 mg ivosidenib daily, the CR+CRh rate was 33% (95% confidence interval [CI] 26-40), median duration of response 8.2 (95% CI 5.6-12) months, and conversion from TD to TI in 37%. These endpoints reflect short-term benefit in patients with an unmet medical need; long-term efficacy outcomes were not assessed. Serious adverse reactions in ≥ 5% of patients were differentiation syndrome (10%), leukocytosis (10%), and QT interval prolongation (7%). Common (≥20%) adverse reactions of any grade were fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema, nausea, mucositis, QT interval prolongation, rash, pyrexia, cough, and constipation. Assessment of long-term safety of ivosidenib is a condition of this approval.