FDA Accepts Application, Grants Priority Review to Vorasidenib for IDH-Mutant Diffuse Glioma


If vorasidenib receives full approval, it would be a first-in-class target therapy to treat individuals with IDH-mutant gliomas.

The FDA has accepted the New Drug Application and granted Priority Review for vorasidenib (Servier) for the treatment of isocitrate dehydrogenase (IDH)-mutant diffuse glioma. A Prescription Drug Unser Fee Act (PDUFA) action date was set for August 20, 2024.1

Chimeric antigen receptor CAR - car T-Cell therapy, CAR T-cell therapy is the use of genetically modified T cells that express a special protein called a chimeric antigen receptor 3d rendering - Image credit: catalin | stock.adobe.com

Image credit: catalin | stock.adobe.com

Vorasidenib is an oral, selective, highly brain-penetrant dual inhibitor of mutant IDH 1 and 2 (IDH1/2) enzymes, according to study authors.1

IDH mutation impacts 20% of individuals diagnosed with primary malignant brain tumors with adult-type diffuse gliomas. The study authors noted that this includes 100% of grade 2 and grade 3 adult-type diffuse gliomas. To properly assess and diagnose an individual, testing for IDH mutations could provide more clarity on the prognosis of the disease.1

Key Takeaways

  1. Vorasidenib, a dual inhibitor of mutant isocitrate dehydrogenase 1 and 2 (IDH1/2) enzymes, has shown significant efficacy in treating IDH-mutant diffuse glioma. It demonstrated notable improvements in progression-free survival (PFS) and time to next intervention (TTNI) compared to placebo in a phase 3 clinical trial.
  2. The acceptance of regulatory submissions by both the FDA and the European Medicine Agency (EMA), along with the granting of priority review status, indicate recognition of the potential therapeutic value of vorasidenib.

"In the realm of glioma treatment, innovation has been stagnant for nearly a quarter-century, posing challenges for patients who, post-surgery, may opt to defer treatment due to concerns around potential toxic side effects. As a drug specifically designed to be highly blood-brain barrier penetrant, vorasidenib has demonstrated clinically meaningful efficacy in patients with IDH1/2 mutant gliomas alongside a consistently manageable safety profile, said Susan Pandya, MD, Head of Cancer Metabolism Global Development Oncology & Immuno-Oncology at Servier, in a press release. “This promising outcome brings hope to patients grappling with IDH-mutant diffuse gliomas, offering a potential breakthrough for those eagerly awaiting a new therapeutic option.”1

The approval was based on findings from the phase 3 global, randomized, double-blind, placebo-controlled INDIGO clinical trial. The study evaluated the tolerability and safety of vorasidenib compared with placebo among individuals with residual or recurrent grade 2 glioma with IDH1/2 who received surgery as their only form of treatment.1

According to study authors, the trial met its primary endpoint of progression-free survival (PFS) per blinded independent review committee (BIRC) and its secondary endpoint of time to next intervention (TTNI) at the prespecified second interim analysis.1

Compared with the placebo, vorasidenib demonstrated significant impact in PFS per BIRC among patients who were randomly assigned to receive the injection (Hazard Ratio [HR], 0.39; 95% Confidence Interval [CI], 0.27 to 0.56; 1-sided P=0.000000067). The median PFS in the placebo group was 27.2 and 11.1 months. Similarly, TTNI was also significant (HR, 0.26; 95% CI, 0.15 to 0.43; 1-sided P=0.000000019), although median TTNI was not met for vorasidenib and was 17.8 for the placebo.1

Other results displayed a reduction in tumor volume with vorasidenib, by 2.5% every 6 months, compared to an increase of 13.9% every 6 months in the placebo group, according to study authors.1

The safety of vorasidenib was consistent with results previously found in the phase 1 trial. Additonally, vorasidenib was reported to have low-grade toxic effects.1,2

"The compelling efficacy results observed with vorasidenib in the INDIGO study underscore its full potential to emerge as the benchmark treatment for patients grappling with IDH-mutant diffuse glioma harboring IDH1/2 mutations," said Claude Bertrand, Executive Vice-President of Research & Development and Chief Scientific Officer at Servier, in a press relase. "The submission of global regulatory filings for vorasidenib serve as validation of Servier’s global oncology commitment while marking a possibly significant milestone for patients who have endured more than 2 decades without access to new therapeutic solutions.”1

The study authors noted that if vorasidenib receives approval, it would be the first-in-class target therapy to treat individuals with IDH-mutant gliomas.1

  1. FDA and EMA Accept Vorasidenib Regulatory Submissions for the Treatment of IDH-mutant diffuse glioma. Servier. News release. February 20, 2024. Accessed February 20, 2024.
  2. Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma. The New England Journal of Medicine. News release. August 17, 2023. Accessed February 20, 2024. https://www.nejm.org/doi/full/10.1056/NEJMoa2304194.
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