FDA Grants Approval to Ivosidenib for Patients With R/R Myelodysplastic Syndromes With IDH1 Mutation

On October 24, 2023, the FDA granted approval for ivosidenib, a small molecule inhibitor of isocitrate dehydrogenase-1 (IDH1), in the treatment of patients with relapsed/refractory (R/R) myelodysplastic syndromes (MDS) with IDH1 mutation, as identified through an FDA-approved diagnostic test. 

Additionally, the FDA approved the use of the Abbott RealTime IDH1 Assay as a companion diagnostic tool to identify patients eligible for ivosidenib treatment. 

The decision to approve ivosidenib was in response to the data abstained from the open-label, single-arm, multicenter AG120-C-001 trial (NCT02074839). This trial included 18 patients diagnosed with R/R MDS, specifically with an IDH1 mutation. The presence of this mutation was identified through diagnostic tests conducted locally or centrally and was confirmed by the Abbott RealTime IDH1 Assay. 

Patients received ivosidenib orally starting at 500 mg continuously for 28-day cycles until disease progression, unacceptable toxicity, or hematologic stem cell transplantation. The median duration of treatment was 9.3 months, with 1 patient undergoing stem cell transplantation after ivosidenib therapy. Efficacy outcomes were measured in accordance with the 2006 International Working Group response for MDS. 

The complete response (CR) rate was 38.9% (95% confidence interval [CI], 17.3 to 64.3), with a median time to CR of 1.9 months (ranging from 1 to 5.6 months). The median duration of CR was unable to be estimated. 
In 9 patients who were initially dependent on red blood cell and/or platelet transfusions, 67% (n = 6) achieved independence from both red blood cell and platelet transfusions during any 56-day post-baseline period. Among the 9 patients initially independent of both red blood cell and platelet transfusions, 78% (n = 7) maintained this independence during any 56-day post-baseline period. 

In terms of safety, the adverse reactions associated with ivosidenib among this patient population were comparable to those associated with ivosidenib monotherapy for acute myeloid leukemia. These adverse reactions include gastrointestinal toxicities, like diarrhea, constipation, mucositis, and nausea. They also include arthralgia, fatigue, cough, myalgia, and rash. Ivosidenib treatment holds the potential risk of QTc prolongation. 

Based on these safety precautions, the prescribing information for ivosidenib contains a Boxed Warning for healthcare professionals and patients. 

Source: 

FDA approves ivosidenib for myelodysplastic syndromes. US Food and Drug Administration. Published October 24, 2023.  https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ivosidenib-myelodysplastic-syndromes