Day One Biopharmaceuticals announces updated FIREFLY-1 data

Day One Biopharmaceuticals announced the recently completed submission of the rolling New Drug Application, NDA, to the U.S. Food and Drug Administration, FDA, for tovorafenib as a monotherapy in relapsed or progressive pediatric low-grade glioma, pLGG. The Company anticipates the FDA will file the rolling NDA by mid-November 2023. The Company initiated the rolling submission of the NDA in May 2023 based on data from the FIREFLY-1 trial with a data cutoff as of December 22, 2022. An updated Clinical Study Report was submitted to the FDA with an additional six months of safety and efficacy data through June 5, 2023. FIREFLY-1 is an open-label, pivotal Phase 2 trial, which treated a total of 137 patients across two study arms. The primary endpoint of the trial is ORR by Response Assessment for Neuro-Oncology High-Grade Glioma criteria. Secondary endpoints include ORR by Response Assessment in Pediatric Neuro-Oncology Low-Grade Glioma, progression-free survival, duration of response, time to response, clinical benefit rate and safety. Updated FIREFLY-1 Data Demonstrate Consistent and Durable Response: RANO-HGG data, the primary endpoint of the trial: 67% ORR; 93% clinical benefit rate; 17% CR; 49% PR; 26% SD; At the time of data cutoff, the median duration of response based on RANO-HGG criteria was 16.6 months. Among a total of 77 treated patients: The median duration of tovorafenib treatment was 15.8 months, with 66% of patients on treatment at the time of data cutoff. Safety data, based on the 137 patients treated in both Arm 1 and Arm 2 of FIREFLY-1, indicated monotherapy tovorafenib to be generally well-tolerated. The vast majority of adverse events were Grade 1 or Grade 2, with most common side effects reported related to tovorafenib being change in hair color, fatigue, maculopapular rash, dry skin, and dermatitis acneiform. The most commonly reported treatment-related lab abnormalities were CPK elevation, LDH elevation, anemia, hypophosphatemia and AST elevation. The NDA submission also included the evaluation of responses by RAPNO-LGG and RANO-LGG. Those results include: RAPNO-LGG data, a key secondary endpoint of the trial: 51% ORR; 82% CBR ; 37% PR; 14% MR; 30% SD. At the time of data cutoff, the median DOR based on RAPNO-LGG criteria was 13.8 months. RANO-LGG data, an exploratory analysis of the trial: 53% ORR ; 83% CBR; 26% PR; 26% MR; 30% SD. At the time of data cutoff, the median DOR based on RANO-LGG criteria was 14.4 months