A new drug for the treatment of a type of brain tumour that strikes young people could soon receive approval by the U.S. Food and Drug Administration. The drug, vorasidenib, could greatly extend the time before further therapy – and eventual resistance – is needed.
In an editorial in the New England Journal of Medicine, David Schiff, MD, the co-director of UVA Cancer Center’s Neuro-Oncology Center, outlines the potential significance of the drug vorasidenib for patients with most low-grade gliomas. The drug was fast-tracked by the FDA in August 2023 based on the strength of the findings, and filings for regulatory approval were made in February 2024. FDA approval is anticipated in the second half of 2024, and its approval in Europe will likely soon follow.
Adult-type diffuse gliomas represent approximately 81% of primary malignant brain tumours. Of those, approximately 20% harbour an isocitrate dehydrogenase (IDH) mutation, including 100% of grade 2 and grade 3 adult-type diffuse gliomas. Approximately 2500 Americans with a median age of only 40 are diagnosed with grade 2 IDH-mutant gliomas each year. The tumours cause steadily increasing disability, eventually become resistant to treatment options and typically prove fatal.
Because of the limited treatment options available, doctors usually take a “watch and wait” approach to managing the brain tumours, holding off on treatment until after the tumour progresses.
In the randomised controlled INDIGO trial, 331 patients received either vorasidenib or placebo. The trial showed that the drug slowed tumour growth significantly and extended the average time until the tumour started growing from 11.1 months to more than 27 months. Vorasidenib also increased the time to next intervention (TTNI), the timeframe before patients need additional treatment such as radio- or chemotherapy.
Schiff, in his editorial, describes the results as “striking.” Vorasidenib’s success could “put a nail in the coffin” of the watch-and-wait approach for such brain tumours, Schiff believes.
“It used to be that we thought of all gliomas as being on a spectrum,” Schiff said. “We now understand that those with the IDH gene mutation have a markedly different biology, outcome and, as this study shows, vulnerabilities that new therapies can exploit.”
If the drug receives approval from the federal Food and Drug Administration, it would become the first targeted therapy for low-grade gliomas. But Schiff notes that there are also other recent advances that are improving our understanding of such gliomas.
“There are still many unanswered questions about how we can best utilise this new medication if and when it receives FDA approval,” Schiff said. “Nonetheless, considering that existing standard therapies for these tumours [radiation and chemotherapy] are tough on patients, with short- and long-term side effects, it will be wonderful to have a useful and very well-tolerated treatment option.”
