Tovorafenib Under Review for Relapsed or Progressive Pediatric Low-Grade Glioma

The Food and Drug Administration (FDA) has accepted for Priority Review the New Drug Application (NDA) for tovorafenib for the treatment of relapsed or progressive pediatric low-grade glioma (pLGG).

Tovorafenib is an oral, brain-penetrant, highly-selective type II RAF kinase inhibitor designed to target a key enzyme in the MAPK signaling pathway. The NDA is supported by efficacy and safety data from the open-label, phase 2 FIREFLY-1 study (ClinicalTrials.gov Identifier: NCT04775485), which included 77 patients 6 months to 25 years of age with relapsed or progressive pLGG. The primary endpoint was overall response rate (ORR), according to the Response Assessment for Neuro-Oncology High Grade Glioma criteria.

Findings showed that among the 69 evaluable patients, the ORR was 67% and the clinical benefit rate was 93%; 17% of patients achieved complete response, 49% achieved partial response, and 26% achieved stable disease. Median duration of response was 16.6 months (95% CI, 11.6, not estimable). Median duration of treatment was 15.8 months; 66% (n=51) of patients were on treatment at the time of data cutoff (June 5, 2023).

The most common adverse reactions reported with tovorafenib were change in hair color (76%), fatigue (44%), maculopapular rash (41%), dry skin (33%), and dermatitis acneiform (30%). Treatment-related lab abnormalities included creatinine phosphokinase elevation, lactate dehydrogenase elevation, anemia, hypophosphatemia, and aspartate aminotransferase elevation. Most of the adverse events were grade 1 or grade 2.

“We are pleased to be one step closer to achieving our mission of bringing a novel targeted therapy to children whose low-grade gliomas with BRAF alterations have relapsed or progressed,” said Jeremy Bender, PhD, CEO of Day One. “We are grateful to the patients and their caregivers who participated in the FIREFLY-1 trial and look forward to continuing to collaborate with the FDA as we prepare to make this treatment more broadly available to those who need it.”

A Prescription Drug User Fee Act target date of April 30, 2024 has been set for the application.

This article originally appeared on MPR