Efficacy of OjeMDA (tovorafenib)

The U.S. Food and Drug Administration (FDA) has granted accelerated approval to OjeMDA (tovorafenib) for patients 6 months and older with relapsed or refractory pediatric low-grade glioma (LGG) harboring a BRAF fusion or rearrangement or a BRAF V600 mutation. The goal of pLGG treatment is to stabilize or shrink the tumor without further disrupting the patient's life.

OjeMDA is an oral, brain-penetrating, highly selective type II RAF kinase inhibitor designed to target a key enzyme in the MAPK signaling pathway. The approval is based on data from the open-label, Phase 2 FIREFLY-1 study (NCT04775485), which included 76 patients with relapsed or refractory pediatric LGG. n> (median age8.5 years) , these patients had active BRAF alterations and had received at least 1 line of prior systemic therapy. According to RANO 2010 standards, patients are required to have at least 1 measurable lesion.

Study participants received OjeMDA orally once weekly until disease progression or unacceptable toxicity occurred. The primary endpoint was overall response rate (ORR) according to Response Assessment in Pediatric Neuro-Oncology Low-Grade Glioma (RAPNO-LGG) criteria.

The results showedORR was 51% (95%CI, 40-63) , of which 37% of patients achieved partial response and 14% achieved mild response. Among responders (n=39), the median duration of response (DOR) was 13.8 months (95% CI, 11.3 - not estimable). 85% of patients had a response that lasted at least 6 months, and 23% had a response that lasted at least 12 months. The median time to response was 5.3 months.

Among patients with BRAF fusions or rearrangements (n=64), the ORR was 52%. In patients with BRAF V600E mutations (n=12), the ORR was 50%. The results also showed that patients who previously received MAPK-targeted therapy (n=45) had an ORR of 49%, The ORR of patients (n=31) who had not previously received MAPK-targeted therapy was 55%.