FDA Approval Summary: Ivosidenib in Combination with Azacitidine for Treatment of Patients with Newly Diagnosed Acute Myeloid Leukemia with an IDH1 Mutation.

ABSTRACT

On May 25, 2022, FDA approved a supplemental application for ivosidenib (Tibsovo; Servier) extending the indication in patients with newly diagnosed IDH1-mutated acute myeloid leukemia (AML) in older adults or those with comorbidities to include the combination with azacitidine. The efficacy of ivosidenib in combination with azacitidine was evaluated in Study AG120-C-009, a phase 3, multicenter, double-blind, randomized (11), controlled study of ivosidenib or matched placebo in combination with azacitidine in adults with previously untreated AML with an IDH1 mutation who were 75 years or older or had comorbidities that precluded use of intensive induction chemotherapy. Efficacy was established on the basis of improved event-free survival and overall survival on the ivosidenib + azacitidine arm [HR, 0.35; 95% confidence interval (CI), 0.17-0.72; P = 0.0038, and HR, 0.44; 95% CI, 0.27-0.73; P = 0.0010], respectively. Furthermore, the rate and duration of complete remission (CR) were improved with ivosidenib versus placebo [CR 47% versus 15%, two-sided P < 0.0001; median duration of CR not estimable (NE; 95% CI, 13.0-NE) months versus 11.2 (95% CI, 3.2-NE) months. The safety profile of ivosidenib in combination with azacitidine was consistent with that of ivosidenib monotherapy, with important adverse reactions including differentiation syndrome (15%) and QT interval prolongation (20%).