FDA Approves Ivosidenib for Myelodysplastic Syndrome

FDA’s approvals center around results from AG120-C-001 (NCT02074839), an open-label, single-arm, multicenter trial of 18 adult patients with relapsed or refractory MDS with an IDH1 variant that was detected in peripheral blood or bone marrow by a local or central diagnostic test and confirmed retrospectively by the Abbott RealTime IDH1 assay.

Ivosidenib was administered orally at a starting dose of 500 mg daily continuously for 28-day cycles until patients experienced disease progression or unacceptable toxicity or required hematopoietic stem cell transplantation. The median treatment duration was 9.3 months. One patient underwent a stem cell transplantation following their ivosidenib treatment.

Efficacy was established by rates of complete (CR) or partial remission (PR), CR+PR duration, and conversion from transfusion dependence to independence. All of the observed responses were CRs at a 38.9% rate (95% CI = 17.3, 64.3). The median time-to-CR was 1.9 months (range = 1.0–5.6 months), and the median CR duration was not estimable (range = 1.9, 80.8+ months).

Among the 9 patients dependent on red blood cell or platelet transfusions at baseline, 6 (67%) became transfusion independent during a 56-day post-baseline period. Of the 9 patients independent of both red blood cell and platelet transfusions at baseline, 7 (78%) remained transfusion independent during a 56-day post-baseline period.

Ivosidenib’s prescribing information contains a boxed warning for differentiation syndrome, which may be life threatening or fatal. The most common adverse reactions were similar to those observed with ivosidenib monotherapy for acute myeloid leukemia (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ivosidenib-first-line-treatment-aml-idh1-mutation), including gastrointestinal toxicities (e.g., diarrhea, constipation, mucositis, nausea), arthralgia, fatigue, cough, myalgia, and rash. Ivosidenib may also cause QTc prolongation.

The review used the Assessment Aid (https://www.fda.gov/about-fda/oncology-center-excellence/assessment-aid), a voluntary submission from the applicant to facilitate FDA’s assessment. It was also granted priority review, breakthrough designation, and orphan drug designation. FDA-expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics).

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.

For assistance with single-patient investigable new drug applications, healthcare professionals may contact the Oncology Center of Excellence’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).