Vorasidenib Approved by FDA for Grade 2 IDH-Mutant Glioma

On August 6, 2024, the FDA approved vorasidenib (Voranigo; Servier Pharmaceuticals) to treat adult and pediatric patients 12 years and older with grade 2 astrocytoma or oligodendroglioma with a susceptible isocitrate dehydrogenase-1 (IDH1) or IDH2 mutation after surgery.¹

"Today's approval of Voranigo is an enormous leap forward in cancer care, and a defining moment for people living with grade 2 IDH-mutant glioma," said Arjun H. Prasad, MPH/MBA, chief commercial officer for Servier Pharmaceuticals, in a statement.² "Voranigo, which is the first breakthrough in this specific disease area in nearly 25 years, offers patients unprecedented improvement in progression-free survival. We are proud to deliver this first-of-its-kind therapy to patients in need, and we remain committed to bringing innovative targeted therapies to people with cancer."

The recommended dose for adults is 40 mg orally once daily until disease progession or unacceptable toxicity.¹ In patients 12 years and older, the recommended dosage is 40 mg orally once daily for patients weighing 88 lb or more, and 20 mg orally once daily for patients weighing less than 88 lb.

The efficacy of vorasidenib was evaluated in the randomized, multicenter, double-blind, and placebo-controlled INDIGO trial (NCTT04164901), which included 331 patients with grade 2 astrocytoma or oligodendroglioma with susceptible IDH1 or IDH2 mutations following surgery.

Patients were randomized 1:1 to receiver either vorasidenib 40 mg orally once daily or placebo. Patients in the placebo group were able to switch to vorasidenib upon documented radiographic disease progression. Patients who had received prior anticancer treatments, including chemotherapy or radiation therapy, were excluded.

The main efficacy outcomes were progression-free survival (PFS) and time to intervention. Additionally, the researchers measured the safety of vorasidenib by assessing common adverse reactions and the presence of any grade 3 or 4 laboratory abnormalities.

The HR for PFS was 0.39 (95% CI, 0.27- 0.56; P < .0001), indicating a significant improvement for patients treated with vorasidenib, and suggesting that vorasidenib reduced the risk of disease progression by 61% compared with placebo.

The median (SD) time to next intervention was not reached for the vorasidenib arm but was 17.8 months for the placebo group. Additionally, the HR for time to next intervention was 0.26 (95% CI, 0.15-0.43; P < .0001), indicating that vorasidenib significantly delayed the time to the next treatment intervention compared with placebo.

Furthermore, vorasidenib was well tolerated, with the most frequently reported adverse reactions being fatigue, headache, COVID-19 infection, musculoskeletal pain, diarrhea, nausea, and seizures.

"Glioma is a unique cancer. Many of the patients I've met are in their 30s and 40s and in the prime of their lives. They have small children and are at the height of their careers. A glioma diagnosis is devastating. Voranigo can offer patients and their families hope for the future," said David K. Lee, MBA, CEO, Servier Pharmaceuticals, in a statement.² "As we advance more targeted therapies, identifying mutations and understanding how these mutations impact cancer and its progression are key to helping the right patients find the right treatment, at the right time. We are humbled to lead the field of IDH-mutant inhibition, and we are committed to researching its applicability in glioma and other cancers."

References

1. FDA approves vorasidenib for grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation. News release. FDA. August 6, 2024. Accessed August 7, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-vorasidenib-grade-2-astrocytoma-or-oligodendroglioma-susceptible-idh1-or-idh2-mutation

2. Servier's Voranigo (vorasidenib) tablets receives FDA approval as first targeted therapy for grade 2 IDH-mutant glioma. News release. Servier Pharmaceuticals. August 6, 2024. Accessed August 7, 2024. https://www.prnewswire.com/news-releases/serviers-voranigo-vorasidenib-tablets-receives-fda-approval-as-first-targeted-therapy-for-grade-2-idh-mutant-glioma-302215991.html