Servier Canada announced the approval and commercial availability of VORANIGO™ (vorasidenib tablets), the first targeted therapy for the treatment of Grade 2 isocitrate dehydrogenase (IDH)-mutant glioma in adults and pediatric patients aged 12 years and older, following surgery. VORANIGO™ offers glioma patients the convenience of a once-daily oral treatment, providing them with an opportunity to actively manage their disease. Canada is the second country after the United States to receive regulatory authorization for VORANIGO™.
Gliomas are the second-most common type of cancer in Canadians under 40 years old and the second-most common cause of cancer-related deaths in this group.1 These slow-growing brain tumours spread within the brain leading to disruptions in neurological function, seizures, and cognitive impairment. 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. The annual incidence of gliomas is approximately six cases per 100,000 individuals worldwide.2
A key concern with low-grade gliomas is their progression to high-grade gliomas, which are harder to treat and carry a poor prognosis. Research shows that 60-70% of patients with gliomas have the targetable IDH mutation that VORANIGO™ addresses.
In healthy human cells, a family of enzymes called isocitrate dehydrogenases (IDH) help break down nutrients and generate energy for cells. Mutations in IDH1 and IDH2 genes are associated with a variety of cancers, where they prevent cells from differentiating or specializing 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.
Vorasidenib, a dual inhibitor of the mutant IDH1 and IDH2 enzymes, was developed for penetration across the blood–brain barrier.5
About the INDIGO Phase 3 Trial (NCT04164901)
VORANIGO’s Canadian approval is based on results from the pivotal Phase 3 INDIGO clinical trial which demonstrated a significant improvement in progression-free survival (PFS) and time to next intervention (TTNI) in patients with Grade 2 IDH-mutant glioma compared to placebo. The international Phase 3 clinical trial was led by Dr. Ingo K. Mellinghoff at Memorial Sloan-Kettering Cancer Centre. Results from the trial were 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).
References:
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1 https://sunnybrook.ca/media/item.asp?c=1&i=2600&f=vorasidenib-tumor-drug#faq
2 Quinn T. Ostrom, PhD, MPH1,2; David J. Cote, BS3,4,5; Mustafa Ascha, MS6; et al https://jamanetwork.com/journals/jamaoncology/article-abstract/2685651
3 https://sunnybrook.ca/media/item.asp?c=1&i=2600&f=vorasidenib-tumor-drug#faq
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 Konteatis Z, Artin E, Nicolay B, et al. Vorasidenib (AG-881): a first-in-class, brain-penetrant dual inhibitor of mutant IDH13 and 2 for treatment of glioma. ACS Med Chem Lett 2020;11:101-107.
6 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. P., Ducray, F., Umemura, Y., Nabors, B., Holdhoff, M., Hottinger, A. F., Arakawa, Y., Sepulveda, J. M., Wick, W., Soffietti, R., … Cloughesy, T. F. (2023). Vorasidenib in idh1- or IDH2-mutant low-grade glioma. New England Journal of Medicine, 389(7), 589–601. https://doi.org/10.1056/nejmoa2304194
