FDA Grants Accelerated Approval to Day One’s Ojemda for Relapsed or Refractory Pediatric Low-Grade Glioma

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Day One Biopharmaceuticals, Inc’s Ojemda (tovorafenib) has been granted accelerated approval by the FDA to treat patients aged 6 months and older with relapsed or refractory (R/R) pediatric low-grade glioma (pLGG) harboring a BRAF fusion or rearrangement, or a BRAF V600 mutation.¹ The regulatory action for Ojemda, which was previously granted FDA priority review,² marks the first systemic therapy to be approved for the treatment of pLGG that harbors BRAF rearrangements, including fusions.

“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, in a press release. “We are very proud that our first approved medicine addresses this serious and life-threatening disease of childhood and adolescence. We are grateful to the pLGG community, including patients and their families, study investigators, non-profit organizations, and advocacy groups, for their collaboration and support as we strive to close the innovation gap for children with cancer awaiting new treatments.”¹

pLGG, the most commonly diagnosed type of brain tumor in children, causes significant tumor- and treatment-associated morbidities that can affect the life trajectory of patients. Approximately 75% of pLGG cases involve a BRAF alteration, which previously had no approved treatments.

“pLGG is a chronic and relentless cancer that can devastate children and their families, often stealing their vision, balance and speech,” Sabine Mueller, MD, PhD, MAS, pediatric neuro-oncologist, University of California San Francisco Benioff Children’s Hospitals, said in the release. “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.”¹

The FDA based the accelerated approval of Ojemda on findings from the pivotal, multicenter, open-label, Phase II FIREFLY-1 trial (NCT04775485). Investigators enrolled patients aged 6 months to 25 years with R/R pLGG harboring an activating BRAF alteration. Enrollment criteria included at least one line of prior systemic therapy, documented evidence of radiographic progression, and at least one measurable lesion per Response Assessment in Pediatric Neuro-Oncology criteria.³

Investigators found that patients administered Ojemda (n = 76) achieved an overall response rate (ORR) of 51% (95% CI, 40%-63%) and median duration of response of 13.8 months (95% CI, 11.3–not estimable). ORR among 64 patients with BRAF fusions or rearrangements administered Ojemda was 52%, whereas ORR was 50% among 12 patients with a BRAF V600 mutation administered Ojemda. Among 45 patients previously administered MAPK-targeted therapy, ORR was 49%, and in 31 patients who did not previously receive MAPK-targeted therapy, ORR was 55%.

In terms of safety, the most common adverse effects (AEs) observed in at least 30% of patients included rash, hair color changes, fatigue, viral infection, vomiting, headache, hemorrhage, pyrexia, dry skin, constipation, nausea, dermatitis acneiform, and upper respiratory tract infection.¹

“This is an exciting moment for children and families living with pLGG who previously had few treatment options if their disease progressed,” Courtney Davies, president and CEO of the Pediatric Brain Tumor Foundation, said in the release. “The approval of Ojemda is a testament to the power of community and industry collaboration to address a critical unmet need for children whose day-to-day living and long-term health outcomes are significantly impacted by pLGG. The potential benefit that a new treatment option provides children living with this disease and their families is crucial. There is so much to celebrate here.”¹

References

1. Day One’s Ojemda (tovorafenib) receives US FDA accelerated approval for relapsed or refractory BRAF-altered pediatric low-grade glioma (pLGG), the most common form of childhood brain tumor. News release. Day One Biopharmaceuticals. April 23, 2024. Accessed April 24, 2024. https://ir.dayonebio.com/news-releases/news-release-details/day-ones-ojemdatm-tovorafenib-receives-us-fda-accelerated

2. Day One Announces FDA Acceptance of NDA and Priority Review for Tovorafenib in Relapsed or Progressive Pediatric Low-Grade Glioma (pLGG). News release. Day One Biopharmaceuticals. October 30, 2023. Accessed April 24, 2024. https://ir.dayonebio.com/news-releases/news-release-details/day-one-announces-fda-acceptance-nda-and-priority-review

3. Kilburn, L.B., Khuong-Quang, DA., Hansford, J.R. et al. The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial. Nat Med 30, 207–217 (2024). https://doi.org/10.1038/s41591-023-02668-y