European Commission Approves Servier's VORANIGO® (vorasidenib) as the First Targeted Therapy for Grade 2 IDH-Mutant Glioma in the EU

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Sep 22, 2025, 08:05 ET

VORANIGO demonstrated significant improvement in progression-free survival with a favorable safety profile in a pivotal Phase 3 study of patients with Grade 2 IDH-mutant glioma

BOSTON, Sept. 22, 2025 /PRNewswire/ -- Servier, an independent international pharmaceutical group governed by a foundation, today announced that the European Commission (EC) has approved VORANIGO^® (vorasidenib) for the treatment of predominantly non-enhancing Grade 2 astrocytoma or oligodendroglioma with an isocitrate dehydrogenase-1 (IDH1) R132 or isocitrate dehydrogenase-2 (IDH2) R172 mutation in adult and adolescent patients aged 12 years and older and weighing at least 40 kg who only had surgical intervention and who are not in immediate need of radiotherapy or chemotherapy. The decision to approve VORANIGO as the first targeted therapy to treat Grade 2 IDH-mutant glioma follows a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) in July 2025.

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 tumors diagnosed in adults younger than 50 years of age. Historically, treatment options have been limited, and tumors continue to grow and infiltrate normal brain tissue without treatment.^1,2,3

"Today's EU approval of VORANIGO is a landmark moment for people in the EU living with IDH-mutated glioma who have been waiting more than two decades for new treatment options. VORANIGO is the first EMA-approved therapy specifically designed to target mutant IDH enzymes in Grade 2 glioma and represents a long-awaited shift in the treatment paradigm. As a leader in precision medicine, we're grateful to the researchers, patients and advocates who have helped expand our understanding of IDH inhibition and bring this breakthrough to the EU," said Islam Hassan, Global Head of Development-Neuro-Oncology & Senior Director, LS/LCM at Servier.

Decisions by the EC are applicable in the 27 member states of the EU, as well as Norway, Liechtenstein, and Iceland.

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 (PFS) and time to next intervention (TTNI) 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%) adverse reactions were fatigue, COVID-19, musculoskeletal pain, diarrhea and seizure.⁴

VORANIGO has also been granted marketing authorization in the United States, Canada, Australia, Israel, the United Arab Emirates, Saudi Arabia, Switzerland, Brazil, the United Kingdom, and Japan. Servier has submitted marketing authorization applications in several other regions as well and reviews by the respective health authorities are ongoing.

Press Contact
Sara Noonan: [email protected]

About Servier
Servier is an independent international pharmaceutical company governed by a nonprofit foundation, committed to making a meaningful social impact for patients and contributing to a sustainable world.

Its unique governance model ensures its independence, while supporting long-term innovation, with 100% of its profits reinvested in the Group's development.

As a world leader in hypertension and venous diseases and major player in cardiometabolism, Servier drives transformative innovation to support patients with chronic conditions and improve their day-to-day lives through a holistic approach, which includes making patient adherence and control a priority across the globe. Its ambition is to become a leading player in rare cancers, which is why the Group invests heavily in oncology, allocating close to 70% of its R&D budget to this field. By leveraging precision medicine, Servier develops therapies that are more targeted and more effective.

Bolstered by its success in oncology, Servier has expanded into neurology, a key driver of future growth. The Group is focused on a select number of neurodegenerative diseases, where accurate patient profiling enables targeted therapeutic responses through precision medicine.

To open up wider access to high-quality, affordable care, Servier also offers an extensive range of generic medicines, building on well-established brands in France, Eastern Europe, and Brazil. In all its activities, and at every stage of the medicine life cycle, the Group integrates the patient's voice.

Headquartered in France, Servier operates in around 140 countries. In 2023-2024, the Group, which employs over 22,000 people worldwide, achieved revenues of €5.9 billion.

More information on the Group website: servier.com

About INDIGO Phase 3 Trial (NCT04164901)⁴INDIGO is a global, randomized, double-blind, placebo-controlled Phase 3 study that was designed to obtain registration for vorasidenib grade 2 glioma with a mutation in the gene encoding isocitrate dehydrogenase 1 or 2 (IDH1 or IDH2) where the only treatment provided was surgery.

The pivotal Phase 3 INDIGO study met its primary endpoint of progression-free survival (PFS) according to the Blinded Independent Review Committee (BIRC) and its key secondary endpoint of time to next intervention (TTNI) at the second pre-specified interim analysis. The primary endpoint, PFS per BIRC, was statistically significant and clinically meaningful in favor of the vorasidenib group. Median PFS was 27.7 months for the vorasidenib group compared with 11.1 months for the placebo group (hazard ratio [HR]: 0.39; 95% confidence interval [CI]: 0.27, 0.56; one-sided P=0.000000067. Although not detailed in the SmPC, results for the key secondary endpoint of time to next intervention (TTNI) at the second pre-specified interim analysis and an exploratory endpoint, tumor growth rate (TGR), were favorable for vorasidenib. TTNI was statistically significant (HR: 0.26; 95% CI: 0.15 to 0.43; P=0.000000019). The median TTNI was not obtained with vorasidenib and was 17.8 months with placebo. Vorasidenib also reduced tumor volume by an average of 2.5% (Tumor Growth Rate -2.5%; 95% CI -4.7% to -0.2%) every 6 months, while tumor volume increased by an average of 13.9% (TGR 13.9%; 95% CI 11.1% to 16.8%) every 6 months in patients randomized to placebo, as measured by an BIRC.

The safety profile in the INDIGO Study was consistent with the results of the Phase 1 trials. Overall, the most common adverse reactions, including laboratory abnormalities, were ALT increased, AST increased, GGT increased, fatigue and diarrhea.

About Glioma⁵Gliomas are tumors that arise from glial or precursor cells within the central nervous system (CNS). The 2021 World Health Organization (WHO) classification recognizes four general groups of gliomas, one of which is adult-type diffuse gliomas. These diffuse gliomas are the most common primary malignant brain tumors in adults. The pathogenesis and prognosis of these tumors are tightly linked to mutations (or lack thereof) in the metabolic enzyme isocitrate dehydrogenase (IDH), and molecular testing is required for proper diagnosis. As of 2021, adult-type diffuse gliomas are sub-divided into only three categories:

Astrocytoma, IDH-mutant (CNS WHO grades 2-4)  
Oligodendroglioma, IDH-mutant and1p19q-codeleted (CNS WHO grades 2-3)  
Glioblastoma, IDH-wildtype (CNS WHO grade 4)

VORANIGO IMPORTANT SAFETY INFORMATION FOR U.S. PATIENTS

What is VORANIGO?

VORANIGO (40 mg tablets) is a prescription medicine used to treat adults and children 12 years of age and older with certain types of brain tumors called astrocytoma or oligodendroglioma with an isocitrate dehydrogenase-1 (IDH1) or isocitrate dehydrogenase-2 (IDH2) mutation, following surgery. Your healthcare provider will perform a test to make sure that VORANIGO is right for you. It is not known if VORANIGO is safe and effective in children under 12 years of age.

What are the possible side effects of VORANIGO?

VORANIGO may cause serious side effects, including:

Liver problems. Changes in liver function blood tests may happen during treatment with VORANIGO and can be serious. Your healthcare provider will do blood tests to check your liver function before and during treatment with VORANIGO. Tell your healthcare provider right away if you develop any of the following signs and symptoms of liver problems:

- yellowing of your skin or the white part of your eyes (jaundice)
- dark tea-colored urine
- loss of appetite
- pain on the upper right side of your stomach area
- feeling very tired or weak

The most common side effects of VORANIGO include:

increased liver enzyme levels in the blood
lack of energy, tiredness
headache
COVID-19
muscle aches or stiffness
diarrhea
nausea
seizure

Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with VORANIGO if you have certain side effects.

VORANIGO may affect fertility in females and males, which may affect the ability to have children. Talk to your healthcare provider if this is a concern for you.
These are not all of the possible side effects of VORANIGO.

Before taking VORANIGO, tell your healthcare provider about all of your medical conditions, including if you:

have liver problems
have kidney problems or are on dialysis
smoke tobacco
are pregnant or plan to become pregnant. VORANIGO can harm your unborn baby

Females who are able to become pregnant:

Your healthcare provider will do a pregnancy test before you start treatment with VORANIGO
You should use effective nonhormonal birth control during treatment with VORANIGO and for 3 months after the last dose. VORANIGO may affect how hormonal contraceptives (birth control) work and cause them to not work well. Talk to your healthcare provider about birth control methods that may be right for you during treatment with VORANIGO
Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with VORANIGO

Males with female partners who are able to become pregnant:

You should use effective birth control during treatment with VORANIGO and for 3 months after the last dose
Tell your healthcare provider right away if your partner becomes pregnant or thinks she may be pregnant during your treatment with VORANIGO

Tell your healthcare provider if you are breastfeeding or plan to breastfeed. It is not known if VORANIGO passes into breast milk. Do not breastfeed during treatment with VORANIGO and for 2 months after the last dose.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. VORANIGO may affect the way other medicines work, and other medicines may affect how VORANIGO works.

Please click here for full prescribing information.

Disclosures
This release contains general information about the Servier Group and its entities (hereinafter "Servier and its Affiliates") and is intended for informational purposes only. The information is thought to be reliable; however, Servier and its Affiliates make no representation as to the accuracy or completeness of the information contained herein or otherwise provided and accept no responsibility or liability, in contract, in tort, in negligence, or otherwise, should the information be found to be inaccurate or incomplete in any respect.

Servier and its Affiliates are not acting as an advisor to the recipient of this information, and the ultimate decision to proceed with any transaction rests solely with the recipient of this information. Therefore, prior to entering into any proposed transaction, the recipient of this information should determine, without reliance upon Servier or its Affiliates, the economic risks and merits, as well as the legal, tax, and accounting characterizations and consequences, of the transaction and that it is able to assume these risks.

This statement also contains forward-looking statements that are subject to varying levels of uncertainty and risk. Investigational new drugs and indications are subject to further scientific and medical review and regulatory approval. They are not approved for use by the FDA.

Any reliance placed on this document is done entirely at the risk of the person placing such reliance. The information contained in this document is neither an offer to sell nor the solicitation of an offer to enter into a transaction.

The content of this document is a summary only, is not complete, and does not include all material information about Servier and its Affiliates, including potential conflicts of interest.

To the maximum extent permitted by applicable laws and regulations, Servier and its Affiliates disclaim all representations, warranties, conditions and guarantees, whether express, implied, statutory or of other kind, nor does it accept any duty to any person, in connection with this document. Without prejudice to the generality of the foregoing, Servier and its Affiliates do not warrant or represent that the information or opinions contained in this document is accurate or complete.

To the maximum extent permitted by applicable laws and regulations, Servier and its Affiliates shall not be liable for any loss, damage or expense whatsoever, whether direct or indirect, howsoever arising, whether in contract, tort (including negligence), strict liability or otherwise, for direct, indirect, incidental, consequential, punitive or special damages arising out of or in connection with this document, including (without limitation) any course of action taken on the basis of the same. The estimates, strategies, and views expressed in this document are based upon past or current data and information and are subject to change without notice.

References

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.
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.
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.
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
Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, Hawkins C, Ng HK, Pfister SM, Reifenberger G, Soffietti R, von Deimling A, Ellison DW. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021 Aug 2;23(8):1231-1251. doi: 10.1093/neuonc/noab106. PMID: 34185076; PMCID: PMC8328013.

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