European Commission (EC) has granted conditional marketing authorisation for tovorafenib as monotherapy for the treatment of patients 6 months of age and older with paediatric low-grade‑glioma harbouring a BRAF fusion or rearrangement, or BRAF V600 mutation, who have progressed after one or more prior systemic therapies. This EC decision applies across all 27 EU Member States, as well as Iceland, Liechtenstein, and Norway.

More than 800 children are diagnosed with BRAF altered paediatric low-grade glioma (pLGG) each year in the EU. This brain tumour, while classified as low-grade (slow progression) carries a profound lifelong burden, frequently leading to significant physical and neurological impairments including loss of vision, speech difficulties and motor dysfunction, which can significantly impact a child’s education, independence and long-term quality of life. 

Until now, many children living with pLGG have had to go through invasive surgeries, multiple lines of chemotherapy, and radiotherapy, often resulting in health complications.

“For children diagnosed with low‑grade glioma, the journey is often long and challenging with limited available treatment options,” said Sandra Silvestri, M.D., PhD, Executive Vice President and Chief Medical Officer, Ipsen.

“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.”

The EC approval is based on data from the pivotal phase II FIREFLY-1 study which evaluated tovorafenib in 137 children and young adults with relapsed or refractory BRAF-altered pLGG who had received at least one prior systemic therapy. The study demonstrated:

• Clinically meaningful tumour response: An overall response rate of 71% per the Response Assessment in Neuro-Oncology criteria for High-Grade Gliomas (RANO-HGG) criteria and 53% per Response Assessment in Pediatric Neuro-Oncology for Low-Grade Glioma (RAPNO-LGG) criteria, with a clinical benefit rate of 77% per RANO-HGG criteria and 58% per RAPNO-LGG criteria.
• Rapid and durable responses: Based on RAPNO-LGG criteria, among responders, the median time to response was 5.4 months with a median duration of response of 18.0 months.
• Manageable safety profile: Tovorafenib was generally well-tolerated, with predominantly Grade 1 or 2 treatment-related adverse events (TRAEs) and a low discontinuation rate (9.5% patients discontinued treatment due to events considered by the investigator to be related to tovorafenib).vii The most common TRAEs were hair colour changes, blood creatine phosphokinase increased, fatigue, anaemia, vomiting, hypophosphataemia, headache, rash maculo-papular, pyrexia, growth retardation, dry skin.
• Convenient Dosing: Once-weekly oral administration, with or without food, in liquid or tablet formulation, minimising disruption to daily family routine.

“Families affected by low-grade glioma often endure years of uncertainty, difficult treatment decisions, and the fear of long-term consequences,” said Professor François Doz, Professor of Pediatrics at Paris Descartes University, Deputy Director of Clinical Research, Innovation and Teaching in the SIREDO Oncology Centre of the Curie Institute (Care, Innovation and research in Cancer of the child, adolescent and young adult) and Director of Teaching of the Hospital Ensemble of the Institut Curie. “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.”

The EU Health Technology Assessment (HTA) Regulation, which began phasing in from January 2025, introduced a new Joint Clinical Assessment (JCA) process to streamline and harmonise the comparative clinical evidence review across EU Member States. Tovorafenib is the first medicine to undergo a JCA evaluation.

Source: Ipsen