お知らせ • Apr 24
Ipsen Receives European Union Approval for Ojemda as Targeted Therapy in Relapsed or Refractory Pediatric Low-Grade Glioma
Ipsen announced that the European Commission (EC) has granted conditional marketing authorization for Ojemda (tovorafenib) as monotherapy for the treatment of patients 6 months of age and older with pediatric low-grade-glioma harboring 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 pediatric low-grade glioma (pLGG) each year in the EU. This brain tumor, 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. 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 tumor 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). The most common TRAEs were hair color changes, blood creatine phosphokinase increased, fatigue, anemia, 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, minimizing disruption to daily family routine. 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 harmonize the comparative clinical evidence review across EU Member States. Ojemda is the first medicine to undergo a JCA evaluation. Tovorafenib (known as Ojemda) is a Type II RAF kinase inhibitor of mutant BRAF V600, wild-type BRAF, and wild-type CRAF kinases. It targets the signaling pathways regulating cell growth and division, which can slow, stop, or shrink cancerous tumors. Tovorafenib is indicated for the treatment of patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma harboring a BRAF fusion or rearrangement, or BRAF V600 mutation. It was approved by the U.S. FDA under accelerated approval based, in part, on response rate and duration of response according to multiple response assessment criteria: Response Assessment in Neuro-Oncology High-Grade Glioma (RANO-HGG) criteria, Response Assessment in Pediatric Neuro-Oncology Low-Grade Glioma (RAPNO-LGG) criteria, and Response Assessment for Neuro-Oncology Low-Grade Glioma (RANO-LGG) criteria. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Tovorafenib is under evaluation as a therapy for patients aged less than 25 years with pLGG harboring BRAF fusion or rearrangement, or BRAF V600 mutation requiring front-line treatment (Phase III FIREFLY-2/LOGGIC). Additional information about FIREFLY-2 may be found at ClinicalTrials.gov, using Identifier NCT05566795 and at CTIS under EUCT number 2024-510742-13-00. The medicine was granted Breakthrough Therapy and Rare Pediatric Disease designations by the FDA for the treatment of patients with pLGG harboring an activating RAF alteration, and it was evaluated by the FDA under priority review. Tovorafenib has also received Orphan Drug designation from the FDA for the treatment of malignant glioma and from the European Commission for the treatment of glioma. Tovorafenib has also been approved in EAU and has been granted Orphan Drug Designation in Russia, Switzerland, Taiwan, Japan South Korea and Australia. Ipsen licensed the ex-U.S. rights to tovorafenib from Day One Biopharmaceuticals Inc. in 2024. FIREFLY-1 is evaluating tovorafenib as once-weekly monotherapy in patients aged 6 months to 25 years with relapsed or progressive pLGG harboring a known activating BRAF alteration. The pivotal and ongoing Phase II FIREFLY-1 study evaluated the safety and efficacy of tovorafenib in 137 relapsed or refractory BRAF-altered pLGG patients, who had received at least one line of prior therapy, across two study arms. Arm 1 (n=77) was used for the efficacy analyses and Arm 2 provided safety data for an additional 60 patients, initiated to enable access to tovorafenib once Arm 1 had fully recruited. Additional information about FIREFLY-1 may be found at ClinicalTrials.gov, using Identifier NCT04775485 and at CTIS under EUCT number 2024-510691-20-00. Pediatric low-grade glioma (pLGG) is a rare childhood brain tumor. More than 800 new cases of BRAF altered pLGG are identified in the European Union each year. BRAF is the gene most commonly altered in pLGG, which include two primary types of BRAF alterations – a BRAF gene fusion and BRAF V600E mutation. These BRAF alterations account for more than 50% of pLGG cases worldwide and until recently there were no approved treatments for patients with pLGG driven by BRAF fusions. pLGG can be chronic and relentless, with patients suffering profound side effects from both the tumor and the treatment, which may include chemotherapy and radiation. These side effects can impact their life over the long term, and may include muscle weakness, loss of vision, and difficulty speaking. This type of tumor has a high risk of progression, and many children with pLGG require long-term treatment. While most children with pLGG survive their cancer, children who do not achieve a complete resection following surgery may face years of increasingly aggressive treatment.
