Servier Announces Promising Phase 1 Data for Vorasidenib in IDH Mutant Low-Grade Glioma Published in Clinical Cancer Research

- Servier's first clinical data manuscript in glioma demonstrates a favorable safety profile and encouraging preliminary activity for vorasidenib in patients with isocitrate dehydrogenase 1 and 2 (IDH1/2) mutant nonenhancing low-grade glioma

- Vorasidenib demonstrated anti-tumor activity and prolonged disease control, with an objective response rate of 18% and median progression-free survival of 3.1 years in a previously treated glioma cohort with recurrent nonenhancing disease

- Registration-enabling global Phase 3 INDIGO trial of vorasidenib is currently enrolling patients with IDH mutant grade 2 residual or recurrent low-grade glioma

News provided by

Servier Pharmaceuticals

Jun 16, 2021, 07:30 ET

BOSTON, June 16, 2021 /PRNewswire/ -- Servier, a growing leader in oncology committed to bringing the promise of tomorrow to the patients we serve, today announced that Clinical Cancer Research has published data from its Phase 1 study evaluating single-agent vorasidenib in isocitrate dehydrogenase (IDH) mutant advanced solid tumors, including low-grade glioma. Vorasidenib is an investigational, oral, selective, brain-penetrant dual inhibitor of mutant IDH1 and IDH2 enzymes.

In the first-in-human study (NCT02481154), vorasidenib demonstrated both a favorable safety profile at doses <100 mg once daily and preliminary clinical activity in recurrent or progressive IDH1/2 mutant low-grade glioma. The study data demonstrated a median progression-free survival of 36.8 months (3.1 years) [95% confidence interval (CI), 11.2–40.8 months] for patients with nonenhancing low-grade glioma. The protocol-defined objective response rate per Response Assessment in Neuro-Oncology criteria for LGG (RANO-LGG) in patients with nonenhancing low-grade glioma was 18% (one partial response, three minor responses). Exploratory evaluation of tumor volumes showed sustained tumor shrinkage in multiple patients with nonenhancing low-grade glioma.

"Given the toxicities associated with chemotherapy and radiation, there remains a significant unmet need to improve treatment options for patients living with IDH mutant low-grade glioma," said Tim Cloughesy, M.D., David Geffen School of Medicine, Department of Neurology, University of California, Los Angeles, an investigator for the Phase 1 study. "These early results reinforce the potential benefit of vorasidenib and the further exploration of more targeted therapies."

Mutations in the metabolic enzymes IDH1/2 occur in up to approximately 80% of patients with low-grade gliomas. Standard treatment of low-grade gliomas includes tumor resection, followed by radiation and chemotherapy as appropriate. This treatment is not curative and current therapy is associated with short- and long-term toxicity, with most patients experiencing disease recurrence and progression to a higher tumor grade. In this study, vorasidenib demonstrated a favorable safety profile. Dose-limiting toxicities of elevated transaminases occurred at doses ≥100 mg and were reversible.

"We are excited to announce the publication of our first clinical data manuscript in glioma in Clinical Cancer Research, underscoring the potential benefit of vorasidenib in IDH mutant low-grade glioma," said Susan Pandya, M.D., Vice President, Clinical Development, Head of Cancer Metabolism Global Development, Servier Pharmaceuticals. "These data provide further support for our registration-enabling Phase 3 INDIGO study evaluating the activity of vorasidenib at an early stage of the disease where delaying the need for more aggressive treatments could provide a meaningful benefit to patients."

Vorasidenib is currently being evaluated in the registration-enabling Phase 3 INDIGO study as a potential treatment for patients with residual or recurrent grade 2 low-grade glioma (NCT04164901).

---

Vorasidenib Phase 1 Dose-Escalation Study

Vorasidenib, an investigational, oral, selective, brain-penetrant dual inhibitor of mutant IDH1 and IDH2 enzymes, is being evaluated as a single agent in an ongoing Phase 1 dose-escalation trial in IDH1/2 mutant advanced solid tumors (n=93), including glioma (n=52). Vorasidenib was administered orally, once daily, in 28-day cycles until progression or unacceptable toxicity. Enrollment was completed in June 2017 (NCT02481154).

Vorasidenib INDIGO Phase 3 Study

Vorasidenib, an investigational, oral, selective, brain-penetrant dual inhibitor of mutant IDH1 and IDH2 enzymes, is currently being evaluated in the registration-enabling Phase 3 INDIGO study as a potential treatment for patients with residual or recurrent grade 2 low-grade glioma (NCT04164901).

About Glioma

Glioma presents in varying degrees of tumor aggressiveness, ranging from slower growing (low-grade glioma) to rapidly progressing (high-grade glioma-Glioblastoma Multiforme). Tumor enhancement is an imaging characteristic assessed by magnetic resonance imaging (MRI), and enhancing tumors are more likely to be high-grade.

Common symptoms of glioma include seizures, memory disturbance, sensory impairment and neurologic deficits. The long-term prognosis is poor, and regardless of treatment, the majority of patients with low-grade gliomas will have recurrent disease that will progress over time. Approximately 11,000 low-grade glioma patients are diagnosed annually in the U.S. and EU and approximately 80% have an IDH mutation.

About Servier Pharmaceuticals

Servier Pharmaceuticals LLC is a commercial-stage company with a passion for innovation and improving the lives of patients, their families and caregivers. A privately held company, Servier has the unique freedom to devote its time and energy toward putting those who require our treatment and care first, with future growth driven by innovation in areas of unmet medical need.

As a growing leader in oncology, Servier is committed to finding solutions that will address today's challenges. The company's oncology portfolio of innovative medicines is designed to bring more life-saving treatments to a greater number of patients across the entire spectrum of disease and in a variety of tumor types.

Servier believes co-creation is fundamental to driving innovation and is actively building alliances, acquisitions, licensing deals and partnerships that bring solutions and accelerate access to therapies. With our commercial expertise, global reach, scientific expertise and commitment to clinical excellence, Servier Pharmaceuticals is dedicated to bringing the promise of tomorrow to the patients that we serve.

More information: www.servier.us

About Servier

Servier is a global pharmaceutical group governed by a Foundation. With a strong international presence in 150 countries and a total revenue of 4.7 billion euros in 2020, Servier employs 22,500 people worldwide. Servier is an independent group that invests over 20% of its brand-name revenue in Research and Development every year. To accelerate therapeutic innovation for the benefit of patients, the Group is committed to open and collaborative innovation with academic partners, pharmaceutical groups, and biotech companies. It also integrates the patient's voice at the heart of its activities.

A leader in cardiology, the ambition of the Servier Group is to become a recognized and innovative player in oncology. Its growth is based on a sustained commitment to cardiovascular and metabolic diseases, oncology and immuno-inflammatory, and neurodegenerative diseases. To promote access to healthcare for all, the Servier Group also offers a range of quality generic drugs covering most pathologies.

More information: www.servier.com

Press contacts

Servier Pharmaceuticals (U.S.)
Megan Talon
[email protected]

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.

SOURCE Servier Pharmaceuticals