Day One Biopharmaceuticals this week announced that the U.S. Food and Drug Administration (FDA) has approved OJEMDA (tovorafenib), a type II RAF inhibitor, for the treatment of patients six months of age and older with relapsed or refractory pediatric low-grade glioma (pLGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation.
BRAF is the most commonly altered gene in pLGG, with up to 75 percent of children having a BRAF alteration. Until now, there had been no medicines approved for patients with pLGG driven by BRAF fusions.
The most common brain tumor diagnosed in children, pLGG causes profound tumor- and treatment-associated morbidities that can impact patients’ life-long health. An estimated 1,100 children per year are eligible for front-line systemic therapy of pLGG, which currently consists of chemotherapy or radiation.
OJEMDA is a Type II RAF kinase inhibitor of mutant BRAF V600, wild-type BRAF, and wild-type CRAF kinases. It is indicated for patients six months of age and older with relapsed or refractory pediatric low-grade glioma (LGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation. It is the only approved systemic therapy for pLGG that offers once-weekly dosing, with or without food, as a tablet or oral suspension.
The drug received accelerated approval, and Day One was also given a rare pediatric disease priority review voucher from the FDA. That program aims to incentivize rare disease drug development.
In a video conference, Samuel Blackman, co-founder and head of research and development at Day One, pointed out that the company had just been founded just a few years ago.
“OJEMDA ushers in a new day for children living with relapsed or refractory pLGG, and we are pleased that we can deliver a new medicine for these patients in desperate need of new treatment options. Moreover, OJEMDA is the first and only FDA-approved medicine for children with BRAF fusions or rearrangements, which are the most common molecular alteration in pLGG,” said Jeremy Bender, PhD, chief executive officer of Day One.
“pLGG is a chronic and relentless cancer that can devastate children and their families, often stealing their vision, balance and speech,” said Sabine Mueller, pediatric neuro-oncologist, University of California San Francisco Benioff Children’s Hospitals.
The disease can go into remission on its own by early adulthood, but by then much damage can already be done.
“The goal of pLGG treatment is to stabilize or shrink the tumor without further disrupting the child’s and family’s life. Historically, there has been no standard of care for children with pLGG who have relapsed. We are excited to welcome a new targeted treatment option with once-weekly oral dosing designed specifically for these kids and their families.”
OJEMDA accelerated approval is based on data from Day One’s pivotal open-label Phase II FIREFLY-1 trial, which enrolled a total of 137 relapsed or refractory BRAF-altered pLGG patients across two study arms. Details of this trial were presented in November 2023 at the Society for Neuro-Oncology meeting through two oral plenary presentations and in parallel through as well as in a report in Nature Medicine.
The FIREFLY trial is being conducted in collaboration with the Pacific Pediatric Neuro-Oncology Consortium (PNOC), which is an international consortium with study sites within the United States, Canada, Europe and Australia dedicated to bringing new therapies to children and young adults with brain tumors.
