FDA Approves Ivosidenib Plus Azacitidine for Previously Untreated IDH1-Mutated AML
On May 25th, 2022 FDA approved TIBSOVO (ivosidenib tablets) in combination with VIDAZA (azacitidine) for the treatment of patients with newly diagnosed IDH1-mutated acute myeloid leukemia (AML) in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy. The news has been scared with a press-release available here.
The Study: The AGILE study (NCT03173248) is a multicenter, double-blind, randomized, placebo-controlled trial that examined ivosidenib plus azacitidine (Vidaza) versus placebo in combination with azacitidine in patients with previously untreated AML with an IDH1 mutation. A total of 146 patients were randomized in the AGILE study with a median age was 75.5 years (range, 70.0–80.0). The ivosidenib/azacitidine arm consisted of 72 patients, the control arm had 74 patients, and the experimental population was made of up 54 patients with de novo AML compared with 18 with secondary AML. Additionally, 16 patients receiving ivosidenib plus azacitidine had poor-risk genetics compared with 20 patients in the placebo plus azacitidine arm.
Results: Efficacy was based on AGILE trial demonstrated a statistically significant improvement in event-free survival (EFS) (hazard ratio [HR] = 0.35 [95% CI 0.17, 0.72], 2-sided p-value = 0.0038)2 and overall survival (OS) (HR = 0.44 [95% CI 0.27, 0.73]; 2-sided p = 0.0010). TIBSOVO plus azacitidine treatment resulted in a threefold improvement in median OS (24 months) compared to placebo plus azacitidine (7.9 months) as a first-line treatment for IDH1-mutated AML.
Additional information: Ivosidenib tablets were previously FDA approved as a single-agent for the treatment of adults with IDH1-mutant relapsed or refractory AML, and for adults with newly diagnosed IDH1-mutant AML who are ≥ 75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy.