FDA Grants Priority Review to Ivosidenib Tablets in IDH1+ R/R MDS

"Today’s filing acceptance provides further support for the potential efficacy and acceptable safety profile of [ivosidenib tablets] in relapsed or refractory MDS and reinforces the importance of mutational testing in this patient population," according to Amir Fathi, MD, program director at the Center for Leukemia at Massachusetts General Hospital and associate professor of Medicine at Harvard Medical School.

The FDA has granted priority review to a supplemental new drug application (sNDA) for ivosidenib tablets (TIBSOVO) as a treatment for patients with IDH1-mutated, relapsed/refractory myelodysplastic syndromes (MDS), according to a press release from Servier.1

The comprehensive clinical data package accompanying the application included updated findings from a phase 1 study (NCT02074839), in which treatment with ivosidenib tablets elicited an objective response rate (ORR) of 83.3% and a complete remission (CR) rate of 38.9% among 18 evaluable patients with MDS. Additionally, the median time to CR was 1.87 months (range, 1.0-5.6), and the median duration of CR was not reached as of the data cutoff point.

Investigators reported a median overall survival (OS) of 35.7 months (range, 3.7-88.7). Of 9 patients who were initially transfusion dependent with red blood cells or platelets, 66.7% were transfusion independent at a minimum of 56 days after baseline.

Treatment-related adverse effects (TRAEs) observed during the study were consistent with previous reports of ivosidenib tablets, and the study treatment did not raise any new safety signals.

“While the novel use of targeted IDH inhibition has been proven across a number of difficult-to-treat cancers, there continues to be a significant unmet need for patients [with] MDS within this molecularly defined subset, especially for those who experience disease progression,” Amir Fathi, MD, program director at the Center for Leukemia at Massachusetts General Hospital and associate professor of Medicine at Harvard Medical School, said in the press release. “Today’s filing acceptance provides further support for the potential efficacy and acceptable safety profile of [ivosidenib tablets] in relapsed or refractory MDS and reinforces the importance of mutational testing in this patient population.”

Investigators of the multi-center phase 1 study evaluated the efficacy, safety, and pharmacokinetics of ivosidenib in advanced hematologic malignancies harboring an IDH1 mutation, including those with relapsed/refractory AML and those with MDS. Patients received oral ivosidenib tablets every day as part of a 28-day cycle until disease progression or unacceptable toxicity.

The study’s primary end point was CR plus partial remission (PR) rate. Secondary end points included duration of CR plus PR, duration of transfusion independence, and time to transfusion independence.

Patients 18 years and older with a documented diagnosis of MDS, relapsed/refractory acute myeloid leukemia (AML), untreated AML, or another IDH1-mutated advanced hematologic malignancy based on local or central evaluation were able to enroll on the trial. Additional eligibility criteria included having an ECOG performance status of 0 to 2, adequate hepatic and renal function, and recovery from any toxicity resulting from prior surgery or radiotherapy.

Those who underwent hematopoietic stem cell transplant within 60 days of beginning study treatment or received systemic anti-cancer therapy within 14 days were not able to enroll on the study. Patients were also ineligible to enroll if they had an active severe infection, a history of myocardial infarction, or known unstable or uncontrolled angina pectoris.

The FDA previously granted breakthrough therapy designation to ivosidenib for treating adult patients with relapsed/refractory MDS harboring an IDH1 mutation in December 2019.²

“This filing acceptance and priority review for [ivosidenib] in patients with relapsed or refractory [MDS] underscores our continued work to advance therapeutic progress across IDH-mutated cancers, and if approved in this setting, will bring the first and only targeted therapy to patients living with a significant unmet need,” Susan Pandya, MD, vice president of Clinical Development and head of Cancer Metabolism Global Development Oncology & Immuno-Oncology at Servier, concluded.

References

1. Servier announces FDA filing acceptance and priority review for TIBSOVO® (ivosidenib tablets) in the treatment of IDH1-mutated relapsed or refractory (R/R) myelodysplastic syndromes (MDS). News release. Servier. August 15, 2023. Accessed August 16, 2023. bit.ly/3OVRguq
2. Agios receives FDA breakthrough therapy designation for TIBSOVO® (ivosidenib) for the treatment of adult patients with relapsed or refractory myelodysplastic syndrome with an IDH1 mutation. News release. Agios Pharmaceuticals, Inc. December 16, 2019. Accessed August 16, 2023. https://shorturl.at/JQV59