FDA D.I.S.C.O. Burst Edition: FDA approval of Ojemda (tovorafenib) for relapsed or refractory pediatric low-grade glioma harboring a BRAF fusion or rearrangement, or BRAF V600 mutation
Regulatory approval: On April 23, 2024, the FDA granted accelerated approval to tovorafenib (Ojemda) for patients aged ≥6 months with relapsed or refractory pediatric low-grade glioma harboring a BRAF fusion/rearrangement or BRAF V600 mutation. Approval was supported by FIREFLY-1, a multicenter, open-label, single-arm trial (n=76) reporting an overall response rate of 51% and a median duration of response of 13.8 months. Common adverse reactions included rash, hair color changes, fatigue, and viral infection.
FDA accelerated approval: tovorafenib (Ojemda) in pediatric low-grade glioma
Type: Regulatory approval (accelerated approval)
Agency/date: US FDA, 2024-04-23
The FDA granted accelerated approval to tovorafenib (Ojemda) for patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma (LGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation.
According to the FDA, this is the first FDA approval of a systemic therapy for pediatric LGG with BRAF rearrangements, including fusions.
Supporting evidence (FIREFLY-1)
Efficacy was evaluated in FIREFLY-1, a multicenter, open-label, single-arm trial enrolling 76 patients with relapsed/refractory pediatric LGG and an activating BRAF alteration detected locally, who had received ≥1 prior systemic therapy. Patients had documented radiographic progression and ≥1 measurable lesion; tumors with additional activating alterations and known/suspected NF1 were excluded. Tovorafenib was administered once weekly (BSA-based) until progression or unacceptable toxicity.
Primary outcome: overall response rate (CR/PR/minor response) by blinded independent central review using RANO LGG criteria.
Results: ORR 51%; median duration of response 13.8 months.
Safety
Most common adverse reactions (>30%): rash, hair color changes, fatigue, viral infection, vomiting, headache, hemorrhage, pyrexia, dry skin, constipation, nausea, dermatitis acneiform, upper respiratory tract infection. Common grade 3/4 lab abnormalities (>2%): decreased phosphate/hemoglobin/albumin/lymphocytes/leukocytes/potassium/sodium; increased CPK/ALT/AST.
More information is available via FDA Drugs@FDA; serious AEs can be reported to MedWatch.