According to a July 27 news release from biopharmaceutical company Day One Biopharmaceuticals (“Day One”), the company’s therapeutic option DAY101 received Rare Pediatric Disease designation within the United States. Altogether, the treatment is designed for patients with pediatric low-grade glioma (pLGG) with an activating RAF alteration. As no current approved treatment options for patients with pLGG exist outside of surgery, chemotherapy, or radiation, DAY101 shows the potential to fulfill an unmet need within this group.

DAY101

First, it is important to understand what DAY101 is. According to Day One, DAY101 is:

an oral and highly selective investigational pan-RF inhibitor currently in clinical development for…patients with relapsed or progressive low-grade glioma, or pLGG. This unique type II RAF-inhibitor has comparably high brain distribution and exposure in comparison to other MAPK pathway inhibitors, thus providing new hope that it may benefit patients with primary brain tumors or brain metastases of solid tumors.

Ultimately, DAY101 is designed to address the RAS-RAF-MEK-ERK signaling pathway to prevent cancer growth and progression. So far, over 250 patients have been treated with DAY101. Altogether, the treatment is relatively safe and well-tolerated. While some side effects have occurred following treatment, these include changes in hair color, as well as skin rashes. According to prior research, DAY101 also shows promise in reducing or preventing tumor growth.

The Rare Pediatric Disease designation was granted by the FDA. This status is given to drugs or biologics designed to treat rare or life-threatening conditions affecting pediatric patients (under 18). In this case, a “rare pediatric disease” is one affecting under 200,000 Americans. Beyond Rare Pediatric Disease status, DAY101 also received Orphan Drug and Breakthrough Therapy designations.

Moving forward, Day One will evaluate the safety, efficacy, and tolerability of DAY101 in the Phase 2 FIREFLY-1 clinical trial. The trial is currently enrolling. To join, patients must have pLGG with BRAF alterations. Learn more about the study here.

Pediatric Low-Grade Glioma (pLGG)

Pediatric low-grade glioma (pLGG) accounts for up to 50% of central nervous system (CNS) tumors in children. According to the Dana-Farber Cancer Institute, pLGG:

are slow-growing tumors. As they grow, they press on surrounding healthy parts of the brain, affecting their function.

pLGG is typically classified based on location in the brain and what type of cell they form from. For example, pLGG can form from astrocytes, ependymocytes, or oligodendrocytes. Although patients may have lasting effects, pLGG is survivable in many cases. Symptoms can include:

• Nausea and vomiting
• Headaches which worsen in the morning
• Changes in mood, behavior, or personality
• Premature puberty
• Unusual sleepiness
• Confusion
• Unintended weight gain or loss
• Vision, hearing, and speech difficulties
  • Note: Vision changes may include blurred or double vision.
• Increased head size (in infants)
• Difficulty walking or balancing
• Seizures