Ivosidenib/Azacitidine Granted Priority Review Designation by FDA for IDH1+ AML

The FDA granted priority review to a supplemental new drug application for oral ivosidenib (Tibsovo) plus azacitidine for patients with untreated IDH1-mutant acute myeloid leukemia (AML), according to a press release from Servier Pharmaceuticals.

The designation, commonly given to therapies that offer major advancements in treatment or fulfill an unmet need, will shorten the combination’s review time from 10 months to 6 months. The application is based on findings from the phase 3 AGILE trial (NCT03173248) which assessed ivosidenib vs placebo plus azacitidine in patients with previously untreated AML and an IDH1 mutation.

“On the heels of our recent FDA approval of [ivosidinib] in cholangiocarcinoma, we are pleased with this important step forward in the agency's consideration to expand its current indication to include the treatment of patients with previously untreated IDH1-mutated [AML],” David K. Lee, chief executive officer at Servier Pharmaceuticals, said in a press release. “We are thrilled with the positive momentum of this program as we continue to grow our leadership in oncology and deliver more life-changing medicines to patients living with difficult-to-treat cancers.”

Findings from the study, which were presented at the 2021 American Society of Hematology Annual Meeting and Exposition, indicated that the combination yielded a significantly improved event-free survival (EFS) vs the placebo arm (HR, 0.33; 95% CI, 0.16-0.69; 1-sided P = .0011). Moreover, ivosidenib and azacitidine resulted in a statistically significant improvement in overall survival (OS; HR, 0.44; 95% CI, 0.27-0.73; 1-sided P = .0005) and a median OS of 24.0 months.

Patients who enrolled on the study were 75 years or older and not eligible for chemotherapy due to comorbidities. The primary end point of the study was EFS, with key secondary end points including complete response rate, OS, and objective response rate.

“TIBSOVO is the first therapy targeting cancer metabolism to demonstrate improved event-free survival and overall survival in combination with azacitidine in patients with previously untreated IDH1-mutated AML,” Susan Pandya, MD, vice president of clinical development and head of cancer metabolism global development oncology & immuno-oncology at Servier Pharmaceuticals, said in a press release. “With this FDA acceptance for Priority Review, we are closer to offering this critical treatment option to patients in the U.S. and we look forward to engaging with regulatory agencies around the world.”

Ivosidenib was previously approved by the FDA as a single agent treatment for patients with relapsed/refractory IDH1-mutated AML over the age of 75 years with comorbidities that made them ineligible for chemotherapy. Ivosidenib was also approved by the FDA in August 2021 for the treatment of patients with IDH1-positive cholangiocarcinoma.

Reference

Servier Announces FDA filing acceptance and priority review for TIBSOVO® (ivosidenib tablets) in combination with azacitidine for patients with previously untreated IDH1-mutated acute myeloid leukemia. News release. Servier. March 7, 2022. Accessed March 7, 2022. https://bit.ly/3vL08d7