Once-Daily Pill Approved to Treat Forms of Astrocytoma and Oligodendroglioma

The Food and Drug Administration (FDA) has approved Voranigo (vorasidenib; Servier, Boston, MA) for the treatment of adults and children aged ≥12 years with Grade 2 astrocytoma or oligodendroglioma with a susceptible isocitrate dehydrogenase-1 (IDH1) or isocitrate dehydrogenase-2 (IDH2) mutation following surgery, which includes biopsy, sub-total resection, or gross total resection. Voranigo is an IDH1 and IDH2 inhibitor available as a tablet for once-daily administration. The medication functions by reducing the activity of the mutant IDH1 and IDH2 enzymes that prevent cells from differentiating properly. These mutations are associated with a variety of cancers.

The approval is based on data from the phase 3 INDIGO clinical trial (NCT04164901), which enrolled 331 participants with residual or recurrent Grade 2 glioma with IDH1 or IDH2 mutations who had undergone surgery as their only treatment. Participants were randomized to receive either Voranigo at 40 mg daily or placebo. The primary endpoint was progression-free survival (PFS) up to 30 months as assessed by a blinded independent review committee (BIRC), with a key secondary endpoint assessing time to next intervention (TTNI) up to approximately 3 years.

The study met its primary endpoint, with participants treated with Voranigo showing a clinically significant improvement in PFS compared with those receiving placebo.

• There was a median PFS of 27.7 months and 11.1 months in the Voranigo and placebo groups, respectively (Hazard Ratio [HR], 0.39; 95% CI, 0.27 to 0.56; 1-sided P<.001).
• The key secondary endpoint was also met, with the Voranigo group showing a significantly prolonged TTNI compared with the placebo group (HR, 0.26; 95% CI, 0.15 to 0.43; 1-sided P<.001).
• Median TTNI was 17.8 months for the placebo group and was not met for the Voranigo group.
• Treatment with Voranigo reduced tumor volume by a mean of 2.5% every 6 months, while placebo was associated with a 13.9% mean tumor volume increase every 6 months.

Common adverse reactions occurring in ≥15% of participants included fatigue, COVID-19, musculoskeletal pain, diarrhea, and seizure.

"Patients living with Grade 2 IDH-mutant gliomas have long faced the harsh reality of an incurable disease with very limited post-surgery treatment options," said Ralph DeVitto, President and CEO of the American Brain Tumor Association. "The FDA approval of VORANIGO marks a monumental breakthrough in glioma treatment, offering renewed hope for patients and their families living with this relentless disease."