Servier’s Voranigo tablets receive FDA approval for brain tumour treatment

Servier announced that the US Food and Drug Administration (FDA) has approved VORANIGO, an isocitrate dehydrogenase-1 (IDH1) and isocitrate dehydrogenase-2 (IDH2) inhibitor, indicated for the treatment of adult and pediatric patients 12 years and older with Grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation following surgery including biopsy, sub-total resection, or gross total resection. VORANIGO is available and offers glioma patients the ability to actively manage their disease with the convenience of a once-daily pill.

Gliomas are types of brain cancer that can hinder normal brain function and cause a variety of symptoms. Diffuse gliomas with IDH mutations represent the most common malignant primary brain tumours diagnosed in adults younger than 50 years of age. They are not curable with current therapies and without treatment, they continue to grow and infiltrate normal brain tissue. (1, 2, 3)

In healthy human cells, a family of genes called isocitrate dehydrogenases (IDH) help break down nutrients and generate energy for cells. Mutations in IDH1 and IDH2 are associated with a variety of cancers, where they prevent cells from differentiating or specialising, into the kind of cells they are ultimately supposed to become. When cells cannot differentiate properly, they may begin to grow out of control.(4) In IDH-mutant gliomas, VORANIGO works by reducing the activity of the mutant IDH1 and IDH2 enzymes, to help control the disease.

The approval of VORANIGO is supported by results from the pivotal Phase 3 INDIGO clinical trial published in ‘The New England Journal of Medicine’ and presented during the Plenary Session at the 2023 Annual Meeting of the American Society of Clinical Oncology (ASCO), which showed that VORANIGO significantly extended progression-free survival and time to next intervention when compared to placebo. The INDIGO study showed that VORANIGO was well tolerated, and its safety profile was consistent with results from the Phase 1 studies. The most common (≥15 per cent) adverse reactions were fatigue, COVID-19, musculoskeletal pain, diarrhoea and seizure.(5)

References:

1. Mandonnet E, Delattre JY, Tanguy ML, et al. Continuous growth of mean tumor diameter in a subset of grade II gliomas. Ann Neurol 2003;53:524-528.

2. Rees J, Watt H, Jäger HR, et al. Volumes and growth rates of untreated adult low-grade gliomas indicate risk of early malignant transformation. Eur J Radiol 2009;72:54-64.

3. Miller JJ, Gonzalez Castro LN, McBrayer S, et al. Isocitrate dehydrogenase (IDH) mutant gliomas: a Society for Neuro-Oncology (SNO) consensus review on diagnosis, management, and future directions. Neuro Oncol 2023;25:4-25.

4. Julie Grisham Monday, J. 1. (2019, July 1). Research clarifies how IDH mutations cause cancer. Memorial Sloan Kettering Cancer Center. https://www.mskcc.org/news/research-clarifies-how-idh-mutations-cause

5. Mellinghoff, I. K., van den Bent, M. J., Blumenthal, D. T., Touat, M., Peters, K. B., Clarke, J., Mendez, J., Yust-Katz, S., Welsh, L., Mason, W.