FDA Approves IDH1/2+ Companion Diagnostic for Vorasidenib in Grade 2 Astrocytoma or Oligodendroglioma

FDA

The FDA has approved the Ion Torrent Oncomine Dx Target Test as a companion diagnostic to identify patients who are eligible for treatment with vorasidenib (Voranigo) tablets.¹

The approval of Thermo Fisher’s companion diagnostic follows the August 6, 2024, FDA approval of Servier Pharmaceuticals’ vorasidenib for the treatment of adult and pediatric patients 12 years and older with grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation following surgery including biopsy, sub-total resection, or gross total resection.²

“[Vorasidenib] is the first and only targeted therapy for patients living with grade 2 IDH-mutant glioma, a relentless and incurable type of brain cancer that hasn’t seen treatment advances in nearly 25 years,” David K. Lee, chief executive officer of Servier Pharmaceuticals, said in a news release.1 “As more targeted therapies become available to patients, identifying key driver mutations is essential to help the right patients find the right treatment, at the right time.”

Approximately 20% of gliomas harbor an IDH mutation, and the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology recommend IDH mutation testing in all patients with glioma. The inclusion of IDH testing has become even more critical with the approval of vorasidenib.1

The approval of vorasidenib was based on findings from the phase 3 INDIGO trial (NCT04164901), which showed that vorasidenib led to a 61% reduction in the risk of disease progression or death vs placebo (HR, 0.39; 95% CI, 0.27-0.56; P < .001). At a median follow-up of 14.0 months (IQR, 10.1-17.9) in the vorasidenib arm and 14.3 months (IQR, 10.0-18.1) in the placebo arm, the median progression-free survival (PFS) was 27.7 months (95% CI, 17.0-not estimated) with vorasidenib (n = 168) vs 11.1 months (95% CI, 11.0-13.7) with placebo (n = 163).^2,3

INDIGO was an international, double-blind, randomized, placebo-controlled trial that enrolled patients at least 12 years of age with residual or recurrent, histologically confirmed grade 2 oligodendroglioma or astrocytoma per WHO 2016 criteria with centrally confirmed IDH1/2 mutations. Mutation variants included were IDH1 R132H, R132C, R132G, R132S, or R132L, and IDH2 R172K, R172M, R172W, R172S, or R172G.³

To be eligible for enrollment patients also needed to have a Karnofsky performance status of at least 80; at least 1 prior surgery, with the most recent occurring between 1 and 5 years prior to random assignment; no other anticancer treatment for glioma; no treatment with glucocorticoids for signs or symptoms of glioma; consideration for a watch-and-wait approach; and adequate hepatic and renal function.

Patients were randomly assigned to receive 40 mg of vorasidenib or matching placebo once daily in 28-day cycles. Treatment continued until disease progression or unacceptable toxicity, or until another anticancer therapy was indicated according to the investigator.

The primary end point was blinded independent review–assessed PFS per RANO-LGG criteria. Secondary end points included time to next therapy, objective response rate, safety, tumor growth rate, health-related quality of life, and overall survival.

“As the health care system works to realize the impact of precision medicine, patients must have access to the proper testing that helps unlock targeted treatment options based on their unique genomic profiles. This access is the driving motivation behind the extensive work we do with pharma partners to help connect the right patients to new therapies as soon as they are approved,” Kathy Davy, president, clinical next-generation sequencing at Thermo Fisher Scientific, stated.¹ “The work we do every day reflects our Mission, and combining our CDx technology with Servier’s breakthrough therapy will help dramatically impact care for patients with aggressive brain tumors.”

The Oncomine Dx Target Test is also approved to identify patients for targeted therapy in non–small cell lung cancer, cholangiocarcinoma, medullary thyroid cancer, and thyroid cancer.¹ 

Thermo Fisher and Servier Pharmaceuticals will continue to develop additional companion diagnostics with the Ion Torrent Oncomine Dx Express Test, which can provide results in as little as a day.¹

References

1. FDA approves NGS-based companion diagnostic for first targeted therapy for patients with grade 2 IDH-mutant glioma. News release. Thermo Fisher Scientific. October 21, 2024. Accessed October 21, 2024. https://newsroom.thermofisher.com/newsroom/press-releases/press-release-details/2024/FDA-Approves-NGS-Based-Companion-Diagnostic-for-First-Targeted-Therapy-for-Patients-with-Grade-2-IDH-Mutant-Glioma/default.aspx
2. FDA approves vorasidenib for grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation. FDA. August 6, 2024. Accessed August 6, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-vorasidenib-grade-2-astrocytoma-or-oligodendroglioma-susceptible-idh1-or-idh2-mutation
3. Mellinghoff IK, van den Bent MJ, Blumenthal DT, et al. Vorasidenib in IDH1- or IDH2-mutant low-grade glioma. N Engl J Med. 2023;389(7):589-601. doi:10.1056/NEJMoa2304194