FDA Approves Vorasidenib for Grade 2 Astrocytoma or Oligodendroglioma With Susceptible IDH1 or IDH2 Variants

This is the first FDA approval for a systemic therapy for patients with grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 variant.

Efficacy was evaluated in 331 patients with grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 variant following surgery enrolled in INDIGO (NCT04164901), a randomized, multicenter, double-blind, placebo-controlled trial. Patients were randomized 1:1 to receive vorasidenib 40 mg orally once daily or placebo orally once daily until they experienced disease progression or unacceptable toxicity. IDH1 or IDH2 variant status was prospectively determined by the Life Technologies Corporation Oncomine Dx Target Test. Patients randomized to placebo were allowed to cross over to vorasidenib after experiencing documented radiographic disease progression. Patients who received prior anticancer treatment, including chemotherapy or radiation therapy, were excluded.

The major efficacy outcome measure was progression-free survival (PFS) using a blinded independent review committee per modified Response Assessment in Neuro-Oncology for Low Grade Glioma criteria. An additional efficacy outcome measure was time to next intervention. The hazard ratio for PFS was 0.39 (95% CI = 0.27, 0.56; p < 0.0001). The median time to next intervention was not reached for the vorasidenib arm and was 17.8 months for the placebo arm (HR = 0.26; 95% CI = 0.15, 0.43; p < 0.0001).

The most common adverse reactions reported in at least 15% of patients during the clinical trial were fatigue, headache, COVID-19 infection, musculoskeletal pain, diarrhea, nausea, and seizure. The most common grade 3 or 4 laboratory abnormalities reported in more than 2% of patients were increased alanine aminotransferase, increased aspartate aminotransferase, GGT increased, and decreased neutrophils.

The recommended vorasidenib dose in adult patients is 40 mg orally once daily until disease progression or unacceptable toxicity. The recommended vorasidenib dose in pediatric patients 12 years and older is based on patient body weight:

• ≥ 40 kg: 40 mg orally once daily
• < 40 kg: 20 mg orally once daily

Full prescribing information for vorasidenib will be posted on Drugs@FDA (https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm). 

The review was conducted under Project Orbis (https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis), an initiative of the FDA Oncology Center of Excellence (OCE). Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For its review, the FDA collaborated with the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency, Health Canada, Switzerland’s Swissmedic, and Israel’s Ministry of Health. The application reviews are ongoing at the other regulatory agencies.

The applicant used the Assessment Aid (https://www.fda.gov/about-fda/oncology-center-excellence/assessment-aid) to facilitate the FDA’s review. The FDA granted the application priority review, fast track designation, breakthrough designation, and orphan drug designation. FDA’s expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics).

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.

For assistance with single-patient applications for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).