FDA approves ivosidenib for myelodysplastic syndromes
Regulatory approval: On Oct 24, 2023, the FDA approved ivosidenib (Tibsovo) for adults with relapsed or refractory myelodysplastic syndromes (MDS) with a susceptible IDH1 mutation detected by an FDA-approved test. Approval was based on the open-label, single-arm AG120-C-001 study (n=18). The FDA also approved the Abbott RealTime IDH1 Assay as a companion diagnostic. Boxed Warning highlights potentially fatal differentiation syndrome; QTc prolongation is also noted.
FDA approval: ivosidenib for IDH1-mutated relapsed/refractory MDS (Oct 24, 2023)
The FDA granted regulatory approval on October 24, 2023 for ivosidenib (Tibsovo; Servier Pharmaceuticals LLC) for adult patients with relapsed or refractory myelodysplastic syndromes (MDS) with a susceptible IDH1 mutation, as detected by an FDA-approved test. The FDA also approved the Abbott RealTime IDH1 Assay as a companion diagnostic.
Evidence base
Approval was based on AG120-C-001 (NCT02074839), an open-label, single-arm, multicenter trial enrolling 18 adults with relapsed/refractory IDH1-mutated MDS. IDH1 mutations were identified locally or centrally from peripheral blood or bone marrow and retrospectively confirmed by the Abbott RealTime IDH1 Assay.
Patients received ivosidenib 500 mg orally once daily in continuous 28-day cycles until progression, unacceptable toxicity, or hematopoietic stem cell transplantation. Median treatment duration was 9.3 months; one patient proceeded to transplantation.
Efficacy outcomes reported
All observed responses were complete remissions (CRs). CR rate: 38.9% (95% CI, 17.3–64.3). Median time to CR: 1.9 months (range, 1.0–5.6). Median CR duration was not estimable (range, 1.9–80.8+ months). Among 9 patients transfusion-dependent at baseline, 6 (67%) became transfusion independent during any 56-day post-baseline period.
Safety highlights
Common adverse reactions were similar to those seen with ivosidenib monotherapy in AML (including GI toxicities, arthralgia, fatigue, cough, myalgia, rash). Labeling includes a Boxed Warning for potentially life-threatening or fatal differentiation syndrome and notes risk of QTc prolongation.