FDA Approves Vorasidenib for Certain Gliomas

The US Food and Drug Administration (FDA) has approved vorasidenib (Voranigo, Servier) for the treatment of certain isocitrate dehydrogenase (IDH)–mutant diffuse gliomas, marking the first approval of a targeted therapy for these types of brain tumors.

Specifically, the oral targeted inhibitor of IDH1 and IDH2 was approved for use after surgery in adults and children aged 12 years or older who have grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation. According to the FDA, surgery includes biopsy, subtotal resection, or gross total resection. 

Mutations in IDH1 are present in around 80% of grade 2 gliomas, whereas IDH2 mutations are more infrequent, occurring in about 4%. 

Prior to the approval, which was based on progression-free survival (PFS) and safety findings from the pivotal phase 3 INDIGO trial, patients with this type of glioma had limited treatment options, said a Servier spokesperson.

The approval of vorasidenib marks “one of the biggest advances in low-grade glioma in more than two decades” and “will empower patients to take active control of their disease with a once-daily pill,” according to the spokesperson.

In the INDIGO trial, 331 patients were randomly assigned to receive 40 mg of vorasidenib once daily (n = 168) or placebo (n = 163). At a median follow-up of 14.2 months, the median PFS was more than twice as long among those who received vorasidenib vs placebo: 27.7 months vs 11.1 months, respectively (hazard ratio [HR] for disease progression or death, 0.39). The time to next intervention was also significantly longer with vorasidenib vs placebo (median not reached vs 17.8 months, respectively; HR, 0.26).

The 61% reduction in the risk for tumor progression or death observed in the trial represents “a significant sign of efficacy that has the potential to change the landscape in this disease,” first author, Ingo K. Mellinghoff, MD, of Memorial Sloan Kettering Cancer Center, New York City, told Medscape Medical News last year, when presenting the findings at the 2023 American Society of Clinical Oncology conference. These findings were simultaneously published in The New England Journal of Medicine.

Glenn Lesser, MD, a discussant at the 2023 meeting, commented on the “striking” findings. The results are “statistically highly significant, and more importantly, they’re clinically very, very significant,” said Lesser, from Wake Forest Baptist Health in Winston-Salem, North Carolina.

Vorasidenib can also potentially delay the use of toxic chemotherapies and radiation for many years in patients with these tumors, Lesser added.

Adverse events of grade 3 or higher occurred in 22.8% of those who received vorasidenib and in 13.5% of those in the placebo group. Increased alanine aminotransferase levels of grade 3 or higher occurred in 9.6 vs 0% of patients in the groups, respectively.

The most common adverse reactions with vorasidenib, affecting at least 15% of treated patients, include fatigue, headache, COVID-19, musculoskeletal pain, diarrhea, nausea, and seizure. The most common grade 3 or 4 laboratory abnormalities were increased alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase as well as decreased neutrophils. 

The recommended dose of vorasidenib for adults is 40 mg given orally once daily until disease progression or unacceptable toxicity. In children aged 12 or older, the recommended dose is 40 mg given orally once daily for those weighing ≥ 40 kg, and 20 mg given orally once daily for those weighing < 40 kg.

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at sworcester@mdedge.com or on Twitter: @SW_MedReporter.