Cloughesy’s Insights on the FDA Approval of Vorasidenib in IDH-Mutant Gliomas

Timothy F. Cloughesy, MD, director of UCLA’s Neuro-Oncology Program, a distinguished professor in neurology, discusses the impact and significance of the FDA’s approval of vorasidenib (Voranigo, formerly AG-881), a first-in-class option for the treatment of patients with IDH-mutant gliomas.

Vorasidenib is an oral, selective, highly brain-penetrant dual inhibitor of mutant IDH1 and IDH2 enzymes. This approval is for the treatment of patients 12 and older with IDH-mutant, grade 2 astrocytoma or oligodendroglioma.

Findings from phase 3 INDIGO trial (NCT04164901) support this approval. Here, vorasidenib significantly improved progression-free survival and delayed the time to the next intervention compared with placebo.

Transcription:

0:09 | I think this provides a real opportunity for all patients if this drug is going to be approved. Again, this opportunity to be able to hold off on radiation and chemotherapy for as long as possible allows these patients who are young, are either in the midst of their careers, are developing their careers, are developing their families, to be able to kind of be at their cognitive best during this time. And I think that is the huge value that we are seeing. Again, we will understand more as data matures, just how long a period of time that could be.

0:50 | But I could say, having treated patients in the phase 1 study, that I have patients who are still on the drug for over 7 years. So we are really talking about substantial periods of time where people can feel they do not have to initiate radiation and chemotherapy, and can maintain their cognitive abilities.

REFERENCES:

1. FDA approves vorasidenib for grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation. News release. FDA. August 6, 2024. Accessed August 6, 2024. https://tinyurl.com/3jv48wa9

2. Mellinghoff IK, van den Bent MJ, Blumenthal DT, et al. Vorasidenib in IDH1- or IDH2-mutant low-grade glioma. N Engl J Med. Published online June 4, 2023. doi:10.1056/NEJMoa2304194

3. Mellinghoff IK, van den Bent MJ, Blumenthal DT, et al. INDIGO: A global, randomized, double-blinded, phase 3 study of vorasidenib versus placebo in patients with residual or recurrent grade 2 glioma with an IDH1/2 mutation. J Clin Oncol. 2023;41(suppl 17):LBA1. doi:10.1200/JCO.2023.41.17_suppl.LBA1