Rare Daily Staff

The U.S. Food and Drug Administration granted Rare Pediatric Disease designation to Day One Biopharmaceuticals’ lead product candidate, DAY101, for the treatment of low-grade gliomas harboring an activating RAF alteration that disproportionately affects children.

Though rare, pediatric low-grade glioma (pLGG) is the most common brain tumor diagnosed in children, accounting for 30 percent to 50 percent of all central nervous system tumors. BRAF wild-type fusions are the most common cancer-causing genomic alterations in pediatric low-grade gliomas. These genomic alterations are also found in several adult and pediatric solid tumors. Currently approved BRAF inhibitors are only active in tumors harboring BRAF V600 mutations, exhibit limited activity in brain tumors, and cannot be used in patients harboring BRAF fusions.

There are no approved therapies for pLGG and current treatment approaches are associated with significant acute and life-long adverse effects. While most children with pLGG survive their cancer, children who do not achieve a cure following surgery may face years of increasingly aggressive therapies that can have lasting effects on learning, cognition, and quality of life. Due to the indolent nature of pLGG, patients receive multiple years of systemic therapy.

“Historical approaches to treating pLGG such as surgery, radiation, and chemotherapy are associated with significant acute and life-long adverse effects and new options are urgently needed,” said Davy Chiodin, chief development officer of Day One. “DAY101 has the potential to become the first approved treatment option specifically for these patients. Receiving Rare Pediatric Disease designation from the FDA underscores the critical value of our focus on pediatric indications at Day One and represents another significant milestone for the DAY101 program as we continue to enroll patients with pLGG in our pivotal phase 2 FIREFLY-1 study.”

DAY101 is an experimental, oral, brain-penetrant, highly selective type II pan-RAF kinase inhibitor designed to target a key enzyme in the MAPK signaling pathway. In addition to FDA Rare Pediatric Disease designation, DAY101 has been granted Breakthrough Therapy designation by the FDA for the treatment of patients with pLGG harboring an activating RAF alteration who require systemic therapy and who have either progressed following prior treatment or who have no satisfactory alternative treatment options. In addition, DAY101 has received Orphan Drug designation from the FDA for the treatment of malignant glioma and orphan designation from the European Commission for the treatment of glioma.

Day One is currently enrolling patients in a pivotal phase 2 clinical trial (FIREFLY-1) of DAY101 in pediatric, adolescent, and young adult patients with recurrent or progressive low-grade glioma harboring a known BRAF alteration.

The FDA grants Rare Pediatric Disease designation for serious and life-threatening diseases that primarily affect children aged 18 years or younger and impact fewer than 200,000 people in the United States. If a New Drug Application in the United States for DAY101 is approved, Day One may be eligible to receive a Priority Review Voucher (PRV) from the FDA, which can be redeemed to obtain priority review for any subsequent marketing application or may be sold or transferred. Most recently, Rhythm Pharmaceuticals sold a priority review voucher to Alexion for $100 million.

Photo: Davy Chiodin, chief development officer of Day One

X