The FDA has granted Breakthrough Therapy Designation to plixorafenib (FORE8394) for adults with BRAF V600E–mutated high-grade glioma, aiming to speed up its development and review.
Plixorafenib is an oral, next-generation BRAF inhibitor designed to work on multiple BRAF mutations while reducing side effects compared with earlier drugs. Early trials show a 67% overall response rate and clinical benefit in over 75% of patients with BRAF-mutated CNS tumors. Responses have lasted a median of 17.8 months, and the drug was generally well tolerated, with fewer than 2% of patients stopping treatment due to side effects.
Ongoing global trials are evaluating plixorafenib in recurrent CNS tumors and other rare BRAF-mutated cancers, with topline results expected by the end of 2026. If results remain positive, the manufacturer plans to seek accelerated FDA approval. This therapy could offer a more effective and safer option for patients with aggressive brain cancers that currently have limited treatment choices.