The FDA has granted accelerated approval to Day One Biopharmaceuticals’ tovorafenib (Ojemda) as a once weekly monotherapy to treat patients with relapsed or refractory pediatric low-grade glioma (pLGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation, the company announced in a release.1
Tovorafenib’s approval represents the first systematic therapy to treat pLGG, the most common type of brain tumor diagnosed in children aged 6 months and older.2 Patients with pLGG may experience tumors and treatment-associated morbidities detrimental to life expectancy. Prior to the approval of tovorafenib, there was no standard of care or therapy available to treat the pediatric disease.
About FIREFLY-1
Trial Name: A Study to Evaluate DAY101 in Pediatric and Young Adult Patients With Relapsed or Progressive Low-Grade Glioma and Advance Solid Tumors (FIREFLY-1)
ClinicalTrials.gov Identifier: NCT04775485
Sponsor: Day One Biopharmaceuticals
Summary: FIREFLY-1 is an ongoing, Phase 2, multi center, open-label study to evaluate the safety and efficacy of oral pan-RAF inhibitor DAY101 in pediatric, adolescent, and young adult patients with recurrent or progressive low-grade glioma or an advanced solid tumor harboring a known RAF alteration.
“pLGG is a chronic and relentless cancer that can devastate children and their families, often stealing their vision, balance and speech,” Sabine Mueller, a pediatric neuro-oncologist at the University of California San Francisco Benioff Children’s Hospitals, said in a release.1 “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.”
The approval of tovorafenib was based on data from the phase 2 FIREFLY-1 trial (NCT04775485), in which the therapy demonstrated an overall response rate of 67% and a clinical benefit rate of 93% in 69 participants. With 136 patients treated in both arms 1 and 2 of the trial, safety data showed that the therapy was well-tolerated by participants.3
The median duration for treatment was 10.8 months. During the trials, most adverse events were grade 1 or grade 2, with a change in hair color (71%), fatigue (50%), and vomiting (43%) as the most common side effects.3
READ MORE: FDA Approves Drug Combo for Young Glioma Patients
For individuals using tovorafenib, the recommended does based on body surface area is 380 mg/m2 once a week by mouth, with the maximum dose being 600 mg weekly.2
“This is a tremendous moment not only for Day One, but also for the broader pediatric brain tumor community,” Samuel Blackman, co-founder and head of research and development at Day One, said in a release.1 “Thanks to the close collaboration between RAPNO and Response Assessment for Neuro-Oncology (RANO) working groups and the patients and families impacted by a pLGG diagnosis, the way we think about measuring response and the goals of therapy for this unique patient population truly evolved. As a pediatric neuro-oncologist, the approval of Ojemda is a dream realized.”
Day One is also currently investigating tovorafenib as a potential front-line therapy compared to chemotherapy in patients aged 6 months to 25 years with pLGG in the phase 3 FIREFLY-2/LOGGIC trial (NCT05566795). The company said it believes data from the trial will satisfy certain post-marketing requirements to the FDA.
Tovorafenib will be available through specialty pharmacy partners Biologics and Onco360.
READ MORE: Oncology Resource Center
References
3. Day One Announces New FIREFLY-1 Data for Tovorafenib (DAY101) and Initiation of Rolling NDA Submission to FDA for Relapsed or Progressive Pediatric Low-Grade Glioma. News Release. Day One Biopharmaceuticals. June 4, 2023. Accessed April 23, 2024. https://ir.dayonebio.com/news-releases/news-release-details/day-one-announces-new-firefly-1-data-tovorafenib-day101-and
