General Information

Ojemda (tovorafenib) is a kinase inhibitor.

Ojemda is specifically indicated for the treatment of patients 6 months of age and older with relapsed or refractory pediatric lowgrade glioma (LGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation.

This indication is approved under accelerated approval based on response rate and duration of response [see Clinical Studies (14)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Dosing/Administration

Confirm the presence of BRAF fusion or rearrangement, or BRAF V600 mutation prior to initiation of treatment with Ojemda. 

The recommended dosage of Ojemda is based on body surface area. Please see dosing tables in the Ojemda drug prescription label. 

• Administer Ojemda orally, once weekly, with or without food.  
• Tablets: Swallow tablets whole with water. Do not chew, cut, or crush.
• For Oral Suspension: See full prescribing information for preparation and administration instructions.

Mechanism of Action

Tovorafenib is a Type II RAF kinase inhibitor of mutant BRAF V600E, wild-type BRAF, and wild-type CRAF kinases. Tovorafenib exhibited antitumor activity in cultured cells and xenograft tumor models harboring BRAF V600E and V600D mutations, and in a xenograft model harboring a BRAF fusion.

Side Effects

Adverse effects associated with the use of Ojemda may include, but are not limited to, the following:

• rash
• hair color changes
• fatigue
• viral infection
• vomiting
• headache
• hemorrhage
•  pyrexia
• dry skin
• constipation
• nausea
• dermatitis acneiform
• upper respiratory tract infection

 Grade 3 or 4 laboratory abnormalities, including: decreased phosphate, decreased hemoglobin, increased creatinine phosphokinase, increased alanine aminotransferase, decreased albumin, decreased lymphocytes, decreased leukocytes, increased aspartate aminotransferase, decreased potassium, and decreased sodium

Clinical Trial Results

The FDA's accelerated approval was based on data from the pivotal open-label Phase 2 FIREFLY-1 trial, which enrolled a total of 137 relapsed or refractory BRAF-altered pLGG patients across two study arms. Arm 1, which accrued 77 patients, was used for the efficacy analyses. Arm 2 provided additional safety data from an incremental 60 patients and was initiated to enable access to tovorafenib once Arm 1 had fully accrued. 

The approval was based, in part, on the major efficacy outcome measure of overall response rate (ORR), defined as the proportion of patients with complete response (CR), partial response (PR), or minor response (MR) by independent review based on Response Assessment in Pediatric Neuro-Oncology Low-Grade Glioma (RAPNO LGG).

In Arm 1, data from the 76 RAPNO LGG evaluable patients include:

• A best ORR of 51%, which included 28% PRs and 11% MRs.
  • The ORR for Ojemda was 52% among the 64 patients with BRAF fusions or rearrangements and 50% for the 12 patients with a BRAF V600 mutation.
  • The ORR was 49% among the 45 patients who had received a prior MAPK-targeted therapy, and 55% among the 31 patients who had not received a prior MAPK-targeted therapy.
• As of the June 5, 2023 data cutoff, the median duration of response by RAPNO LGG was 13.8 months. In addition, 66% of patients remained on study and continue on treatment as of this date.
• The median time to response, following initiation of treatment, with Ojemda was 5.3 months.
• Based on RANO LGG criteria, the ORR was 53%.