FDA Expands Ivosidenib’s Indication to Newly Diagnosed AML

On May 2, 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.

In July 2018, the FDA initially approved ivosidenib for the treatment of adult patients with relapsed or refractory IDH1-mutated AML, making it the first IDH1 inhibitor approved for this indication. The most recent approval makes ivosidenib the only IDH1 inhibitor approved in the newly diagnosed setting.

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 percent of patients achieved a complete remission (CR), and 42.9 percent 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 were still in remission.

The most common adverse events included diarrhea, fatigue, decreased appetite, edema, nausea, leukocytosis, arthralgia, abdominal pain, dyspnea, and myalgia. Seven participants (25%) experienced differentiation syndrome, six of whom (86%) 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: Agios press release, May 2, 2019.