European Commission Approves Tovorafenib in BRAF+ Pediatric Low-Grade Glioma

The European Commission has granted conditional marketing authorization to tovorafenib (Ojemda) as a monotherapy for the treatment of pediatric patients aged 6 months or older with pediatric low-grade glioma harboring a BRAF fusion or rearrangement, or a BRAF V600 mutation, who progressed after at least 1 prior systemic therapy.¹

According to the news release, this decision marks the first time a targeted therapy has been approved in the European Union specifically for this patient population regardless of BRAF alteration. Tovorafenib is an oral, selective, type II RAF kinase inhibitor designed to target BRAF V600, wild-type BRAF, and wild-type CRAF kinases.

This regulatory milestone followed the April 2024 accelerated approval of the agent by the FDA for the same indication.²

“Families affected by low-grade glioma often endure years of uncertainty, difficult treatment decisions, and the fear of long-term consequences,” François Doz, MD, MSc, professor of pediatrics at Paris Descartes University, deputy director of Clinical Research, Innovation and Teaching in the SIREDO Oncology Centre of the Curie Institute, and director of Teaching of the Hospital Ensemble of the Institut Curie, stated in the press release.¹ “The approval of a targeted therapy like tovorafenib represents a major step forward, offering families not only a new treatment option, but a renewed optimism.”

Both the FDA and European Commission’s decisions were made based on supporting results from pivotal phase 2 FIREFLY-1 trial (NCT04775485), which evaluated the efficacy of tovorafenib in patients with heavily pretreated pediatric low-grade glioma.

What were the efficacy findings from FIREFLY-1?

In the primary efficacy population of 137 children and young adults with BRAF-altered disease, the overall response rate (ORR) and disease control rate (DCR) were 53% and 58% according to the Response Assessment in Neuro-Oncology Pediatric Low-Grade Glioma (RAPNO-LGG) criteria, and 71% and 77%, respectively, per Response Assessment in Neuro-Oncology criteria for High-Grade Gliomas (RANO-HGG) criteria. Utilizing RAPNO-LGG criteria, the median time to response was 5.4 months and the median duration of response was 18.0 months.

At the 30th Annual Meeting & Education Dar of the Society for Neuro-Oncology, updated results from arm 1 of FIREFLY-1 trial were shared.³ The median progression-free survival was 16.6 months (95% CI, 10.9-22.0). Exploratory analyses also revealed that the time-to-next-treatment was 42.6 months (95% CI, 36.7-not evaluable).

How was the phase 2 FIREFLY-1 trial designed?

The FIREFLY-1 study was an open-label, multicenter trial designed to assess tovorafenib in pediatric and young adult patients with RAF-altered, recurrent or progressive low-grade glioma and advanced solid tumors.⁴ To be eligible for enrollment, patients had to be between 6 months and 25 years of age and have a documented BRAF-altered low-grade glioma that had progressed after at least 1 prior line of systemic therapy. Those with a known diagnosis of neurofibromatosis type 1 were excluded from trial participation.

The treatment regimen consisted of tovorafenib administered orally at a dose of 420 mg/m² weekly according to dose rounding guidelines. Notably, tovorafenib was given with or without food, in liquid or tablet formulation. Arm 1 included patients utilized in the efficacy analyses, and arm 2 enrolled an additional 60 patients to provide safety data.

What safety data were observed with tovorafenib treatment?

The safety profile of tovorafenib in the FIREFLY-1 trial was consistent with previously reported data and was generally considered manageable by investigators. The most frequently reported adverse events of any grade included hair color changes, blood creatine phosphokinase increased, fatigue, anemia, vomiting, and hypophosphataemia were among the most common treatment-related adverse events. Most TRAEs were grade 1 or 2, and the rate of discontinuation due to tovorafenib was 9.5%.

“For children diagnosed with low-grade glioma, the journey is often long and challenging with limited available treatment options,” added Sandra Silvestri, MD, PhD, executive vice president and chief medical officer at Ipsen.¹ “Today’s approval is a meaningful step forward for these children, and their families, while reinforcing our commitment to addressing high unmet need. Now, our focus is on ensuring that eligible children across Europe can access this therapy as quickly as possible.”

References

1. Ojemda approved in the European Union as the first targeted therapy in relapsed or refractory pediatric low-grade glioma regardless of BRAF alteration. News release. Ipsen. April 23, 2026. Accessed April 23, 2026. https://tinyurl.com/yjmy74yw
2. FDA grants accelerated approval to tovorafenib for patient with relapsed or refractory BRAF-altered pediatric low-grade glioma. News release. FDA. April 23, 2024. Accessed April 23, 2025. https://shorturl.at/nHOPW
3. Day One announces three year follow-up data from OJEMDA™ (tovorafenib) phase 2 FIREFLY-1 trial at the 2025 Society for Neuro-Oncology (SNO) Annual Meeting. News release. Day One Biopharmaceuticals. November 24, 2025. Accessed April 23, 2026. https://tinyurl.com/57emhyua
4. A study to evaluate tovorafenib (DAY101) in pediatric and young adult patients with relapsed or progressive low-grade glioma (FIREFLY-1). ClinicalTrials.gov. Updated April 10, 2025. Accessed April 23, 2026. https://tinyurl.com/582wycf8