Type II RAF inhibitor tovorafenib for the treatment of pediatric low-grade glioma

Introduction: Pediatric low-grade glioma (pLGG) is the most common childhood brain tumor and is considered a chronic disease. On April 23, 2024, the U.S. FDA approved tovorafenib (OJEMDA™, formerly DAY101), a type II RAF inhibitor, for patients aged six months and older with relapsed or refractory (R/R) pLGG harboring a BRAF fusion, rearrangement, or BRAF V600E mutation.

Areas Covered: This article reviews the pharmacological properties, efficacy, and safety of tovorafenib in treating R/R pLGG. A systematic search of PubMed and Web of Science was conducted for English-language publications on tovorafenib, including journal articles and conference abstracts, up to August 20, 2024.

Expert Opinion: As the first and only FDA-approved therapy for children with BRAF fusions or rearrangements—the most common molecular alteration in pLGG—tovorafenib offers strong central nervous system penetration without triggering the paradoxical MAPK pathway activation observed with type I BRAF inhibitors. Phase 1 and pivotal Phase 2 trials have shown that tovorafenib monotherapy is generally well-tolerated and demonstrates promising, rapid, and sustained clinical activity in children and young adults with BRAF-altered pLGG.