On June 7, 2021 Servier, a growing leader in oncology committed to bringing the promise of tomorrow to the patients we serve, reported updated data from an ongoing perioperative study confirming robust biomarker suppression and reduced tumor cell proliferation with treatment of single-agent vorasidenib and TIBSOVO (ivosidenib tablets) in low-grade glioma with an IDH1 mutation (Press release, Servier, JUN 7, 2021, View Source [SID1234583685]). The data were featured in an oral presentation at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, which is being held virtually.

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IDH mutations occur in approximately 80% of low-grade gliomas, promoting tumorigenesis through increased levels of the oncometabolite D-2-hydroxyglutarate (2-HG). Data from the ongoing perioperative study found that treatment with vorasidenib 50 mg and TIBSOVO 500 mg resulted in mean percent reduction in 2-HG (95% CI) of 92.6% (76.1, 97.6) and 91.1% (72.0, 97.0), respectively, relative to untreated samples in patients with low-grade glioma.

"The updated data demonstrate that robust 2-HG suppression by vorasidenib and TIBSOVO resulted in positive changes in both the tumor cells and the tumor immune microenvironment," said Ingo Mellinghoff, M.D., Memorial Sloan Kettering Cancer Center, an investigator for the study. "These findings underscore that the mutant IDH enzyme plays an active role in the growth of low-grade gliomas and that IDH inhibition may play a significant role in the future treatment of these tumors."

The study data demonstrated that short-term treatment with vorasidenib and TIBSOVO reduced tumor cell proliferation, altered the epigenetic state, and promoted the expression of genes associated with cellular differentiation. Additionally, the data showed that treatment with vorasidenib and TIBSOVO activated interferon signaling and increased T-cell infiltration.

"These early results further support the role of IDH inhibition in treating patients with hard-to-treat cancers, including IDH mutant low-grade glioma," said Susan Pandya, M.D., Vice President, Clinical Development, Head of Cancer Metabolism Global Development, Servier Pharmaceuticals. "These data build on evidence that vorasidenib demonstrates anti-tumor activity through 2-HG suppression and we look forward to confirming the clinical benefit of vorasidenib in patients with IDH mutant low-grade gliomas in the global Phase 3 INDIGO study."

TIBSOVO (ivosidenib tablets) is currently approved in the U.S. as monotherapy for the treatment of adults with IDH1-mutant relapsed or refractory acute myeloid leukemia (AML) and for adults with newly diagnosed IDH1-mutant AML who are ≥75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy.

Vorasidenib, an investigational, oral, 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 glioma.

Perioperative Study of Vorasidenib and TIBSOVO

Vorasidenib and TIBSOVO are being evaluated as a single agent in an ongoing perioperative study in IDH1-mutant Grade 2/3 glioma. The primary endpoint is 2-hydroxyglutarate (2-HG) concentration in tumors resected following presurgical treatment with vorasidenib and TIBSOVO compared with untreated control tumors. Patients were randomized to 500 mg TIBSOVO once daily, 50 mg vorasidenib once daily or the control arm in cohort 1; and 250 mg TIBSOVO twice daily or 10 mg vorasidenib once daily in cohort 2. Patients were treated for four weeks prior to surgery and had the option to continue postoperative treatment until disease progression.

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 somatic mutations in IDH1 and IDH2 occur in approximately 80% of low-grade gliomas.