FDA grants accelerated approval to tovorafenib for patients with relapsed or refractory BRAF-altered pediatric low-grade glioma
Regulatory approval: On April 23, 2024, the FDA granted accelerated approval to tovorafenib (Ojemda) for patients aged ≥6 months with relapsed or refractory pediatric low-grade glioma harboring a BRAF fusion/rearrangement or BRAF V600 mutation. Approval was based on overall response rate and duration of response from the single-arm FIREFLY-1 trial; continued approval may depend on confirmatory evidence of clinical benefit.
FDA accelerated approval: tovorafenib for BRAF-altered pediatric LGG (2024-04-23)
Type: Regulatory approval (accelerated approval)
On April 23, 2024, the FDA granted accelerated approval to tovorafenib (Ojemda; Day One Biopharmaceuticals, Inc.) for patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma (LGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation. The agency noted this as the first FDA approval of a systemic therapy for pediatric LGG with BRAF rearrangements (including fusions).
Supporting evidence
Efficacy and safety were evaluated in FIREFLY-1 (NCT04775485), a multicenter, open-label, single-arm trial of 76 patients with relapsed/refractory pediatric LGG with an activating BRAF alteration, ≥1 prior systemic therapy, radiographic progression, and measurable disease. Key exclusions included tumors with additional activating alterations (e.g., IDH1/2, FGFR) and known/suspected NF1. Tovorafenib was administered once weekly.
Primary endpoint: ORR (CR/PR/MR) by BICR using RAPNO-LGG criteria.
- ORR: 51% (95% CI, 40–63)
- Median DoR: 13.8 months (95% CI, 11.3–not estimable)
The FDA stated accelerated approval was based on ORR and DoR; continued approval may be contingent on confirmatory trials.
Safety (selected)
Common adverse reactions (≥30%) included rash, hair color changes, fatigue, viral infection, vomiting, headache, hemorrhage, pyrexia, dry skin, constipation, nausea, dermatitis acneiform, and upper respiratory tract infection.
Regulatory notes
The application received priority review, breakthrough therapy designation, and orphan drug designation.