A History Making FDA Drug Approval for the Most Common Brain Tumor in Children

The story of tovorafenib (DAY101) is not just about a drug; it's about the transformative power of collaboration, innovation, and unwavering dedication to improving the lives of patients around the world. The historic April 23, 2024, FDA approval is a very important milestone for pediatric cancer drug development. It’s also a catalyst for future innovation, and a testament to the power of multistakeholder collaboration in driving innovation and progress in pediatric cancer research. It serves as a beacon of hope for countless families affected by pediatric cancers.

Pediatric low grade glioma (pLGG) is the most common brain tumor diagnosed in children, representing approximately 30% of pediatric brain tumors. It is a chronic and relentless cancer that can devastate children and their families, often stealing their vision, balance and speech. BRAF is the most commonly altered gene in pLGG, with up to 75% of children having a BRAF alteration. Until tovorafenib, there has been no standard of care for children with pLGG driven by BRAF fusions who have relapsed. This achievement celebrates critically important research by investigators at Dana-Faber Cancer Institute in Boston, to understand the underlying biology of pLGG. This research program identified the predominance of RAS/RAF/MAPK alterations in pLGG.

During the multi-year process of conducting extensive preclinical studies of many synthesized compounds, the Dana-Faber research team discovered one compound, now known as tovorafenib, as having significant activity in an array of tumors. They approached then owner of the compound, Millennium Pharmaceuticals, to request support to launch the first-in-pediatrics study of tovorafenib - the Phase I PNOC clinical trial known as PNOC014. Shortly after this promising clinical trial was initiated, Millenium was acquired by Takeda Pharmacuticals who decided to cease development of the drug in adults. This decision threatened the continued availability of tovorafenib for pediatric studies.

A team of committed pediatric brain cancer champions at Takeda convinced company leadership to license the drug to Day One Biopharmacuticals who had seen the potential and expressed interest in moving the program forward. Less than two years after Day One licensed and renamed the molecule DAY 101, Day One in collaboration with PNOC launched the second trial - PNOC026/FIREFLY-1. A Phase II, multicenter study to evaluate safety and efficacy in pediatric patients with BRAF-altered, recurrent or progressive pLGG, it was the impressive results of PNOC026/FIREFLY-1 that led to the FDA approval.

"Tovorafenib’s development in pLGG started with early clinical trials through PNOC. We are grateful to them for their collaboration on the clinical trials and for the critical role they played in partnership with Day One, the foundation and the patient community. With tovorafenib’s approval, we have put children at the forefront of oncology drug development and pediatric oncologists will now have a new medicine to offer their pLGG patients.” said Dr. Sam Blackman, Founder and Head of Research at Day One Biopharmaceuticals.

The approval of tovorafenib is a victory for children and their families fighting pLGG. This targeted treatment option is a once-weekly oral dosing designed specifically for these kids and their families. Able to be taken at home with minimal side effects, it offers patients optimal quality of life, with children able to avoid the lengthy hospital stays pediatric brain cancer treatments often necessitate.

We are grateful for everyone who has been a part of the tovorafenib story: the patients and their families who participated in the PNOC clinical trials, as well as the multitude of investigators, nurses, research coordinators that have been instrumental in developing the trials, collecting the information, presenting it to the company and eventually to the FDA, Day One Biopharmacuticals for their commitment to pediatric cancer drug development, and of course to everyone who has contributed philanthropic support to fuel this critically needed work.

For information on current PNOC clinical trials click here. To find out if your child is eligible to enroll in a PNOC clinical trial, contact the closest participating site or contact us the PNOC Operations team info@pnoc.us.