A committee of the European Medicines Agency (EMA) has recommended the approval of Ipsen‘s tovorafenib for the treatment of pediatric low-grade glioma (pLGG).
If authorized by the European Commission, the therapy would become a new targeted option for children 6 months and older with a BRAF mutation who have not responded to prior systemic treatments.
Low-grade glioma is the most common form of pediatric brain cancer. While the European Commission is not legally bound by the recommendations from the Committee for Medicinal Products for Human Use (CHMP), it typically follows them within a few months. Tovorafenib is already available in the U.S. under the brand name Ojemda for the same patient population.
“For children diagnosed with pediatric low‑grade glioma, the journey is long and complex, with limited treatment options and no clear standard of care,” Christelle Huguet, PhD, executive vice president and head of research and development at Ipsen, said in a company press release. “Innovating in pediatric oncology is challenging, and genuine breakthroughs are rare. The evidence supporting tovorafenib, which acts on tumor 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.”
Targeting the genetic drivers of tumor growth
BRAF is a protein that helps regulate cell growth, and in many pLGG tumors, mutations in this protein contribute to the uncontrolled growth of cancer cells. The most common cancer-driving BRAF mutations include a specific change to the genetic code called V600, as well as fusions or rearrangements (when the gene that encodes the protein gets mixed up with other genes). The CHMP opinion covers the use of tovorafenib for these common mutations.
Tovorafenib is designed to block the activity of the mutant BRAF protein and other related proteins. It is already conditionally approved in the U.S. under the name Ojemda for the same indication that’s currently being sought in Europe. The oral therapy is available in liquid and tablet formulations; it is taken once weekly with or without food.
The CHMP’s positive opinion was based on data from a Phase 2 study called FIREFLY-1 (NCT04775485), which tested tovorafenib in 137 pediatric patients with BRAF-altered pLGG that had come back (relapsed) or failed to respond (refractory) after at least one prior systemic therapy. Results showed most patients responded to treatment, depending on the specific criteria used to define a response; overall response rates ranged from 53% to 71%. Median time to response was slightly less than six months, and median duration of response was about 1.5 years.
Most safety issues reported in the FIREFLY-1 study were non-serious. About one in 10 patients discontinued tovorafenib due to side effects. The most common side effects of the therapy include hair color changes, fatigue, anemia, and elevated creatine phosphokinase levels (a marker of muscle damage).
“Treatment options for relapsed/refractory pediatric 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 [mutation],” said Olaf Witt, MD, director of translational pediatric oncology at Hopp Children’s Cancer Center, Heidelberg, in Germany. “As a treating physician, I am encouraged by the prospect of introducing a new treatment option for this challenging condition in Europe.”
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