FDA Expands Ivosidenib’s Indication to Newly Diagnosed AML

On May 2, 2019, The U.S. Food and Drug Administration (FDA) approved an expanded indication for the IDH1 inhibitor ivosidenib to include the treatment of adult patients with newly diagnosed, IDH1-mutated acute myeloid leukemia (AML) who are older than 75 years or have comorbidities that make them ineligible to receive intensive induction chemotherapy.

The agency initially approved ivosidenib in July 2018 for the treatment of adult patients with relapsed or refractory IDH1-mutated AML, making it the first IDH1 inhibitor approved for this indication.

The FDA’s decision to expand ivosidenib’s indication was based on a review of data from a phase I study of 28 adults with IDH1-mutated AML who were 75 years or older or had comorbidities that precluded intensive induction chemotherapy. After treatment with ivosidenib 500 mg daily, 28.6% of patients achieved a complete remission (CR), and 42.9% achieved either CR or CR with partial hematologic improvement (CRh). At one year of follow-up, seven of the 12 patients (58.3%) who achieved CR/CRh remained in remission.

The most common adverse events (AEs) associated with ivosidenib included diarrhea, fatigue, decreased appetite, edema, nausea, leukocytosis, arthralgia, abdominal pain, dyspnea, and myalgia. Seven participants (25%) experienced differentiation syndrome, six (86%) of whom recovered.

The supplemental New Drug Application was granted priority review and accepted under the FDA’s Real-Time Oncology Review pilot program, through which the FDA can access clinical trial data before the information is formally submitted to the agency.

Source: FDA news release, May 2, 2019.