Health Canada Approves First and Only Oral Targeted Treatment for Brain Cancer

LAVAL, QC, Oct. 22, 2024 /CNW/ – Servier Canada is pleased to announce 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™.

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).

INDIGO, the pivotal Phase 3 clinical trial met its major efficacy outcome of progression free survival (PFS) per a blinded independent review committee (BIRC) and key secondary endpoint of time to next intervention (TTNI) at the prespecified second interim analysis.

Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma | New England Journal of Medicine

Authors: Ingo K. Mellinghoff, Martin J. van den Bent, Deborah T. Blumenthal, Mehdi Touat, Katherine B. Peters, Jennifer Clarke, Joe Mendez, Shlomit Yust-Katz, Liam Welsh, Warren P. Mason, François Ducray, Yoshie Umemura, Burt Nabors, Matthias Holdhoff, Andreas F. Hottinger, Yoshiki Arakawa, Juan M. Sepulveda, Wolfgang Wick, Riccardo Soffietti, James R. Perry, Pierre Giglio, Macarena de la Fuente, Elizabeth A. Maher, Steven Schoenfeld, Dan Zhao, Shuchi S. Pandya, Lori Steelman, Islam Hassan, Patrick Y. Wen, and Timothy F. Cloughesy, for the INDIGO Trial Investigators.

Ingo K. Mellinghoff is the principal investigator of INDIGO Trial.

Ingo K. Mellinghoff, MD, FACP, serves as Chair of the Department of Neurology and Chief of the Brain Tumor Service at Memorial Sloan Kettering Cancer Center, holding the Evnin Family Chair in Neuro-Oncology. A medical oncologist, Dr. Mellinghoff specializes in the diagnosis, treatment, and management of central nervous system (CNS) tumors, particularly low-grade gliomas and glioblastomas. He leads a multidisciplinary team focused on primary brain tumors, metastases, neurological complications from cancer, and rehabilitation. Dr. Mellinghoff is principal investigator of trials including one on Vorasidenib, an oral inhibitor targeting IDH1- and IDH2-mutant gliomas.

Mechanism of Action: Vorasidenib is a small molecule inhibitor that targets isocitrate dehydrogenase-1 and 2 (IDH1 and IDH2) enzymes. In vitro, vorasidenib inhibited the IDH1 wild type and mutant variants, including R132H and the IDH2 wild type and mutant variants. In cell-based and in vivo tumor models expressing IDH1 or IDH2 mutated proteins, vorasidenib decreased production of 2-hydroxyglutarate (2-HG) and partially restored cellular differentiation.

Voranigo Side effects

The most common Voranigo side effects are

• tiredness
• headache
• muscle or joint pain
• diarrhea
• nausea
• seizures.
• Changes in laboratory tests (Grade 3 or 4) were ALT increased, AST increased, GGT increased, and neutrophils decreased.

Hepatotoxicity: Changes in liver function blood tests may happen during treatment with Voranigo. Including:

• jaundice
• dark tea-colored urine
• loss of appetite
• pain on the upper right side of stomach area
• weekness

Healthcare professionals and organizations shared about this on social media:

MJ Lim-Fat, Assistant Professor at Department of Medicine University of Toronto:

“Grateful for the commitment of our incredible patients participating in brain tumor research. Your courage drives us closer to breakthroughs. Together we’re making strides against brain cancer.”

Brain Cancer Canada:

“Brain Cancer Canada is ecstatic to share that Servier Canada has received Health Canada | Santé Canada Canada authorization for VORANIGO™ (Vorasidenib oral tablets) in the treatment of Grade 2 IDH-Mutant Glioma.

Approximately 60-70% of patients with Grade 2 IDH mutant gliomas have a targetable mutation that a new oral therapy, VORANIGO™, may benefit.

In the Phase 3 INDIGO clinical trial, VORANIGO™demonstrated an extended median progression-free survival of 16.6 months, significantly delaying the need for further treatments.

Gliomas are the second most common type of cancer in patients under 40 years old, they can progress from low-grade to high-grade, and they are the second-most common cause of cancer-related deaths in the age group.

Funding directed to brain cancer research and clinical trials has made this tremendous milestone possible.

While we celebrate, we remain acutely aware that there are still a few more steps to ensure brain cancer patients across Canada have access to the treatment.

Brain Cancer Canada is continuing its advocacy so that:

1. VORANIGO ™️ receives recommendation from Canada Drug Agency for listing in every provincial and territorial drug formulary;

2. Terms for reimbursement are determined such that brain cancer patients will have access to the treatment;

3. Funds continue to be raised and invested in supporting the pathway from the research bench to the patient – accelerating brain cancer clinical trials, like the one that has led to this major treatment advancement.”

Thermo Fisher Scientific:

“The FDA has approved a new test from Thermo Fisher that can help improve care for patients with aggressive brain tumors. The test can help identify patients eligible for Servier Pharmaceuticals’ VORANIGO® tablets, the first and only FDA-approved treatment for Grade 2 IDH-mutant astrocytoma and oligodendroglioma, a rare and relentless brain cancer that hasn’t seen treatment advancements in nearly 25 years. This approval underscores the importance of precision medicine and the critical role genomic testing plays in matching patients with potentially life-changing therapies at the right time.”

For more information visit oncodaily.com