Servier Announces Positive Findings from Longer-Term Analysis of the Phase 3 INDIGO Trial Showing Continued Durable Treatment Effect of VORANIGO® (vorasidenib) Published in The Lancet Oncology

• Data from an additional six months of follow up in patients with Grade 2 mutant IDH 1/2 glioma following surgical intervention published in The Lancet Oncology
• Patients treated with VORANIGO showed reduced tumor volume and seizure frequency compared to placebo 

BOSTON, Nov. 3, 2025 /PRNewswire/ -- Servier today announced longer-term data from the Phase 3 INDIGO trial evaluating VORANIGO^® (vorasidenib) versus placebo in patients with Grade 2 mutant isocitrate dehydrogenase 1 or 2 (mIDH1/2) glioma following surgical intervention and for whom chemoradiotherapy can be delayed were published in The Lancet Oncology. The analysis reports an additional six months of placebo-controlled, double-blind data collected between the second interim analysis data cutoff on September 6, 2022, and trial unblinding on March 7, 2023. These positive results confirm and strengthen the previous findings from the INDIGO pivotal trial.

"These longer-term results from the INDIGO trial build upon VORANIGO's previously demonstrated clinical benefits and demonstrate reductions in tumor volume and seizure frequency in patients with IDH-mutated gliomas," said Becky Martin, PhD, Chief of Medical, Servier Pharmaceuticals. "One year after the FDA approval of VORANIGO, we're immensely proud to have delivered this first-of-its-kind targeted therapy to thousands of patients living with IDH-mutated glioma, offering them clinically meaningful and durable treatment benefits supported by more than a decade of research."

As of data cutoff on March 7, 2023, median follow-up was 20.1 months. Key findings from the newly published analysis include:

•  Median progression-free survival (PFS) improved with VORANIGO (not estimable [NE] [95% CI, 22.1-NE]) compared to placebo (11.4 [95% CI, 11.1-13.9] months), with the hazard ratio (HR) continuing to favor VORANIGO (HR, 0.35 [95% CI, 0.25-0.49]; p<0.0001*). PFS was the primary endpoint of the trial.
• Imaging-based disease progression per blinded independent review committee (BIRC) occurred in 32% of patients receiving VORANIGO versus 64% receiving placebo.
• Prespecified subgroup analyses continued to show that PFS per BIRC was consistent across all subgroups, favoring VORANIGO over placebo.
• Median time to next intervention (TTNI) also improved with VORANIGO versus placebo (NE versus 20.1 months, respectively; HR, 0.25 [95% CI, 0.16-0.40]; p<0.0001*), reflecting durability of disease management. TTNI was a key secondary endpoint of the trial.
• Treatment with VORANIGO reduced tumor growth rate and seizure frequency over placebo with no observed negative effects on health-related quality of life (HRQoL) or neurocognition. 
• An exploratory analysis of patients experiencing one or more seizures showed that rates of on-treatment seizures per person-year were lower in patients receiving VORANIGO (18.2 seizures per person-year [95% CI, 8.4-39.5]) than in those receiving placebo (51.2 seizures per person-year [95% CI, 22.9-114.8]; p=0.026). 
• The safety profile of VORANIGO was consistent with previously reported data. The most commonly reported Grade ≥3 or worse treatment-emergent adverse events (TEAEs) were increased alanine aminotransferase (10%), increased aspartate aminotransferase (5%), seizures (4%) and increased gamma-glutamyltransferase (3%). No new safety signals were detected and fewer than 5% of patients discontinued treatment due to an adverse event. There were no treatment-related deaths.

*The reported P-values are nominal and were not prespecified or adjusted for multiplicity; therefore, the results should be interpreted with caution. 

"For decades, patients with Grade 2 IDH-mutated gliomas had limited treatment options. While surgery was often the first line treatment option for glioma, total resection was rarely achievable because tumors continue to grow and infiltrate the brain even after surgery," said Timothy Cloughesy, M.D., David Geffen School of Medicine, Department of Neurology, University of California, Los Angeles, investigator for the INDIGO trial. "The longer-term data from the INDIGO trial demonstrate that targeted IDH inhibition can fundamentally alter the growth trajectory of certain gliomas, leading to gradual tumor shrinkage." 

These data were previously presented at the 2024 Society for Neuro-Oncology Annual Meeting (SNO). VORANIGO was approved by the U.S. Food and Drug Administration (FDA) in August 2024 after receiving Fast Track Designation and became the first and only FDA-approved targeted treatment for Grade 2 IDH-mutant glioma.

The Phase 3 INDIGO trial is ongoing. Servier plans to present longer-term follow-up results from the largest dataset to date in IDH-mutant glioma, with remarkable overall response rates and PFS outcomes not previously reported in a cohort this size.

Media Contact
Darby Malkin: [email protected]

About Servier in Oncology
Servier is a global leader in oncology, governed by a non-profit foundation. Servier approaches innovation with a long-term vision, free of influence from fiduciary responsibilities. 

Servier is the leader in IDH-mutant targeted therapies and devotes more than 65% of its research and development budget to Oncology. Servier aspires to advance more targeted therapies by identifying mutations and understanding how these mutations impact cancer and its progression. Servier believes we can serve more people by helping the right patients find the right treatment, at the right time.

Servier takes a One Innovation Engine approach to R&D and is actively seeking alliances, partnerships and acquisitions at various stages of the portfolio.

For more information about working with Servier to bring the promise of tomorrow to the patients it serves, visit Servier.us.

About the INDIGO Phase 3 Trial (NCT04164901) ¹
INDIGO, the pivotal Phase 3 clinical trial, was a registration-enabling Phase 3 global, randomized, double-blind placebo-controlled study of vorasidenib in patients with residual or recurrent Grade 2 glioma with an isocitrate dehydrogenase 1/2 (IDH1/2) mutation who have undergone surgery as their only treatment.

As of March 7, 2023, 331 patients were randomized globally to receive VORANIGO 40 mg daily (n=168) or placebo (n=163) continuously in 28-day cycles. Of the 331 patients, 172 had oligodendroglioma (88 VORANIGO; 84 placebo) and 159 patients had astrocytoma (80 VORANIGO; 79 placebo). 

About Glioma ²
Gliomas 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

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
1. 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 

2. 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. 

SOURCE Servier Pharmaceuticals