FDA Accepts Filing for Priority Review for Ivosidenib to Treat IDH1-Mutated R/R MDS

This week, FDA accepted the filing for priority review for ivosidenib (Tibsovo) tablets for the treatment of patients with isocitrate dehydrogenase 1 (IDH1)-mutated relapsed or refractory (R/R) myelodysplastic syndromes (MDS). Servier, the maker of ivosidenib, announced the filing in a statement Tuesday.¹

If approved, ivsosenib would be the first targeted therapy approved for patients with MDS who have a susceptible IDH1 mutation, according to the statement. Priority review is granted to applications for medicines that, if approved, would provide significant improvements in the effectiveness or safety of the treatment, diagnosis, or prevention of serious conditions, according to information from the FDA.

In the United States, ivosidenib is approved as a monotherapy to treat IDH1-mutant R/R acute myeloid leukemia (AML) and as a monotherapy or in combination with azacitidine for adults with newly diagnosed IDH1-mutant AML who are at least 75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy.

“Servier continues to drive our leadership in the scientific innovation behind targeted mutant IDH inhibition, transforming the treatment landscape for thousands of patients living with difficult and hard-to-treat cancers," Susan Pandya, MD, vice president for clinical development and head of cancer metabolism global development oncology and immuno-incology, Servier, said in the statement.

“This filing acceptance and priority review for [ivosidenib] in patients with relapsed or refractory myelodysplastic syndromes 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.”

The filing is based on results from a pivotal phase 1, open label study (NCT02074839) in patients with IDH1-mutated R/R MDS that was presented at the recent European Hematology Association Hybrid Congress. Results showed that ivosidenib demonstrated durable remissions, including complete responses (CRs) in 38.9% of the patients, as well as an acceptable safety profile.²

Results reported at EHA include the following:

• An objective response rate of 83.3%
• Median time to CR of 1.87 months, with a range of 1.0 to 5.6 months
• At the time of data cutoff, the median duration of CR had not been reached, and the median overall survival was 35.7 months
• Of 9 patients who were transfusion dependent with red blood cells or platelets at baseline, 66.7% (n = 6) became independent of transfusions during any ≥56-day post baseline period

"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 MDS patients within this molecularly defined subset, especially for those who experience disease progression," said Amir Fathi, MD, program director of the Center for Leukemia at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School.

"Today's filing acceptance provides further support for the potential efficacy and acceptable safety profile of [ivosidenib] in relapsed or refractory MDS and reinforces the importance of mutational testing in this patient population."

Reference

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. PR Newswire. August 15, 2023. Accessed August 18, 2023. https://www.prnewswire.com/news-releases/servier-announces-fda-filing-acceptance-and-priority-review-for-tibsovo-ivosidenib-tablets-in-the-treatment-of-idh1-mutated-relapsed-or-refractory-rr-myelodysplastic-syndromes-mds-301901315.html

2. DiNardo C. Updated substudy results for ivosidenib in IDH1-mutant relapsed/refractory myelodysplastic syndrome. Poster #724. European Hematology Association Congress; June 8–15, 2023; Frankfurt, Germany, and Virtual.