On October 30, 2023 Day One Biopharmaceuticals (Nasdaq: DAWN) ("Day One" or the "Company"), a clinical-stage biopharmaceutical company dedicated to developing and commercializing targeted therapies for people of all ages with life-threatening diseases, reported that the U.S. Food and Drug Administration (FDA) accepted its New Drug Application (NDA) for tovorafenib as a monotherapy in relapsed or progressive pediatric low-grade glioma (pLGG) (Press release, Day One, OCT 30, 2023, View Source [SID1234636438]). The FDA has granted priority review and assigned a Prescription Drug User Fee Act (PDUFA) target action date of April 30, 2024. The FDA is not currently planning to hold an advisory committee meeting to discuss the application.

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pLGG is the most common brain tumor diagnosed in children, with patients suffering profound tumor and treatment-associated morbidities that can impact their life trajectory. For the vast majority of patients in the relapsed setting, there is no standard of care and no approved therapy.

"We are pleased to be one step closer to achieving our mission of bringing a novel targeted therapy to children whose low-grade gliomas with BRAF alterations have relapsed or progressed," said Jeremy Bender, Ph.D., chief executive officer of Day One. "We are grateful to the patients and their caregivers who participated in the FIREFLY-1 trial and look forward to continuing to collaborate with the FDA as we prepare to make this treatment more broadly available to those who need it."

The NDA is based on results from the open-label, pivotal Phase 2 trial evaluating tovorafenib as a once-weekly monotherapy in patients aged 6 months to 25 years with relapsed or progressive pLGG. Updated data was recently disclosed when the Company announced the completion of its rolling NDA submission on September 11, 2023. New, detailed data is expected to be presented at an upcoming medical conference.

Under the FDA’s Rare Pediatric Disease Priority Review Voucher program, the Company may receive a voucher if it receives an approval for an eligible indication, which can be redeemed to obtain priority review for a subsequent marketing application for a different product candidate.

Tovorafenib is an investigational therapy that is not approved for commercial use in any country.

About Pediatric Low-Grade Glioma

Pediatric low-grade glioma (pLGG) is the most common brain tumor diagnosed in children, accounting for 30% – 50% of all central nervous systems tumors. BRAF wild-type fusions are the most common cancer-causing genomic alterations in pLGG. These genomic alterations are also found in severe adult and pediatric solid tumors.

Pediatric low-grade glioma can impact a child’s health in many ways depending on tumor size and location, including vision loss and motor dysfunction. There are no approved therapies for the vast majority of patients with pLGG, and current treatment approaches are associated with potential acute and life-long adverse effects. While most children with pLGG survive their cancer, children who do not achieve remission following surgery may face years of increasingly aggressive treatment. Due to the indolent nature of pLGG, patients generally receive multiple years of systemic therapy.

About FIREFLY-1

FIREFLY-1 is evaluating tovorafenib as once-weekly monotherapy in patients aged 6 months to 25 years with relapsed or progressive pLGG harboring a known activating BRAF alteration. The trial is being conducted in collaboration with the Pacific Pediatric Neuro-Oncology Consortium (PNOC). The primary endpoint is overall response rate (ORR), defined as the proportion of patients with confirmed response based upon Response Asessment for Neuro-Oncology High Grade Glioma (RANO-HGG) criteria. Secondary and exploratory endpoints include the overall response rate based on Response Assessment in Pediatric Neuro-Oncology Low-Grade Glioma (RAPNO-LGG) criteria, Response Assessment for Neuro-Oncology Low-Grade Glioma (RANO-LGG) criteria and volumetric analyses, progression-free survival, safety, functional outcomes, and quality of life measures. RANO-HGG, RANO-LGG and RAPNO-LGG are assessed by blinded independent central review. Additional information about FIREFLY-1 may be found at ClinicalTrials.gov, using Identifier NCT04775485.

About the Pacific Pediatric Neuro-Oncology Consortium

The Pacific Pediatric Neuro-Oncology Consortium (PNOC) 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.

About Tovorafenib

Tovorafenib is an investigational, oral, brain-penetrant, highly-selective type II RAF kinase inhibitor designed to target a key enzyme in the MAPK signaling pathway, which is being investigated in primary brain tumors or brain metastases of solid tumors. Tovorafenib has been studied in over 325 patients to date and is currently under evaluation in two pivotal clinical trials for pLGG. Tovorafenib is also being evaluated alone or as a combination therapy for adolescent and adult patient populations with recurrent or progressive solid tumors with MAPK pathway aberrations (FIRELIGHT-1).

Tovorafenib has been granted Breakthrough Therapy and Rare Pediatric Disease designations by the U.S. Food and Drug Administration (FDA) for the treatment of patients with pLGG harboring an activating RAF alteration. Tovorafenib has also received Orphan Drug designation from the FDA for the treatment of malignant glioma, and from the European Commission (EC) for the treatment of glioma.