Ipsen, a global biopharmaceutical company with a focus on bringing transformative medicines to patients in three therapeutic areas: oncology, rare disease and neuroscience, has announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending the conditional marketing authorization of Ojemda (tovorafenib) as monotherapy for the treatment of patients 6 months of age and older with paediatric low-grade glioma (pLGG) harbouring a BRAF fusion or rearrangement or BRAF V600 mutation, who have progressed after one or more prior systemic therapies.
More than 800 new cases of BRAF altered pLGG are identified in the European Union each year, causing multiple disabilities including sight, speech, and other neurological problems that profoundly impact the lives of children and their families. The treatment journey for these patients is also complex, often involving invasive surgeries, multiple lines of intensive chemotherapy and radiotherapy over many years, leading to lifelong health issues and developmental complications.
“For children diagnosed with paediatric low-grade glioma, the journey is long and complex, with limited treatment options and no clear standard of care,” said Christelle Huguet, EVP and head of research & development, Ipsen. “Innovating in paediatric oncology is challenging, and genuine breakthroughs are rare. The evidence supporting tovorafenib, which acts on tumour growth driven by an abnormal BRAF gene, is an important development. The positive CHMP opinion moves us closer to delivering a meaningful targeted therapy for these patients and their families.”
If approved, Ojemda (tovorafenib) is expected to be the first and only targeted medicine in European Union for children with relapsed or refractory BRAF-altered paediatric low-grade glioma, irrespective of the type of BRAF alteration.
The decision is based on data from the pivotal phase II FIREFLY-1 study which demonstrated clinically meaningful and durable tumour responses with a positive impact on children’s lives.
Today, there is no global uniform consensus on standard of care for most children as they progress with this rare brain tumour, and there is a considerable need for approved therapies that can minimize long-term morbidities and maintain or improve overall quality of life.
“Treatment options for relapsed/refractory paediatric low-grade glioma have remained limited for decades, which is why a targeted therapy like tovorafenib has the potential to transform how we manage this disease in particular the most common subtype carrying the BRAF-Fusion oncogene,” said Professor Olaf Witt, Director, Translational Paediatric Oncology, Hopp Children's Cancer Center Heidelberg. “As a treating physician, I am encouraged by the prospect of introducing a new treatment option for this challenging condition in Europe.”
The CHMP’s positive opinion 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.
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 Paediatric 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). Common TRAEs included hair colour changes, elevated creatine phosphokinase, fatigue and anaemia.
Convenient Dosing: Once-weekly oral administration, with or without food, in liquid or tablet formulation, minimizing disruption to daily family routine.
Following this positive opinion, the European Commission will review the CHMP’s recommendation, with a final decision on marketing authorization expected in the coming months.
Tovorafenib is a Type II RAF kinase inhibitor of mutant BRAF V600, wild-type BRAF, and wild-type CRAF kinases. It targets the signalling pathways regulating cell growth and division, which can slow, stop, or shrink cancerous tumours.
In the US, tovorafenib is indicated for the treatment of people 6 months of age and older with relapsed or refractory paediatric low-grade glioma harbouring a BRAF fusion or rearrangement, or BRAF V600 mutation. It was approved by the US 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 Paediatric 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 harbouring BRAF fusion or rearrangement, or BRAF V600 mutation requiring front-line treatment (phase III FIREFLY-2/LOGGIC).
The medicine was granted Breakthrough Therapy and Rare Paediatric Disease designations by the FDA for the treatment of patients with pLGG harbouring 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 granted Orphan Drug Designation in South Korea. |