FDA D.I.S.C.O. Burst Edition: FDA approval of Tibsovo (ivosidenib) in combination with azacitidine for newly diagnosed acute myeloid leukemia with a susceptible IDH1 mutation, as detected by an FDA-approved test in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy
Welcome back to the D.I.S.C.O., FDA’s Drug Information Soundcast in Clinical Oncology, Burst Edition, brought to you by FDA’s Division of Drug Information in partnership with FDA’s Oncology Center of Excellence. Today we’ll provide another quick update on a recent FDA cancer drug approval. On May 25, 2022, the FDA approved ivosidenib (brand name Tibsovo) in combination with azacitidine for newly diagnosed acute myeloid leukemia with a susceptible IDH1 mutation, as detected by an FDA-approved test in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy.
Approval was based on a randomized, multicenter, double-blind, placebo-controlled study that included 146 patients with newly-diagnosed acute myeloid leukemia with an IDH1 mutation who met at least one of the following criteria: age 75 years or older, baseline Eastern Cooperative Oncology Group performance status of 2, severe cardiac or pulmonary disease, hepatic impairment with bilirubin greater than 1.5 times the upper limit of normal, creatinine clearance less than 45 mL/min, or other comorbidity. Patients were randomized 1:1 to receive ivosidenib, 500 mg daily, or matched placebo orally once daily, on Days 1-28 in combination with azacitidine 75 mg/m2/day on Days 1-7 or Days 1-5 and 8-9 of each 28-day cycle until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation.
Efficacy was established based on improvements in event-free-survival, overall survival , and rate and duration of complete remission. Event-free-survival was defined as the time from randomization until treatment failure, relapse from remission, or death from any cause, whichever occurred first. Treatment failure was defined as failure to achieve complete remission by 24 weeks. Event-free-survival events occurred in 65% of patients on the ivosidenib plus azacitidine arm and 84% on the placebo plus azacitidine arm. Median overall survival was 24.0 months in the ivosidenib plus azacitidine arm and 7.9 months in the placebo plus azacitidine arm. Complete remission was 47% in the ivosidenib plus azacitidine arm and 15% in the placebo plus azacitidine arm. Median duration of complete remission was not estimable in the ivosidenib plus azacitidine arm and 11.2 months in the placebo plus azacitidine arm.
Prescribing information contains a Boxed Warning alerting health care professionals and patients about the risk of differentiation syndrome which may be life-threatening or fatal.
This review used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application about 6 weeks ahead of the FDA goal date.
Full prescribing information for these approvals can be found at www.fda.gov/drugsatFDA.
Health care professionals should report serious adverse events to FDA’s MedWatch Reporting Program at www.fda.gov/medwatch.
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