One quirk of the most common type of pediatric brain cancer is that as a child gets older, the tumors eventually stop growing. The reasons for this tumor senescence aren’t fully understood, but pediatric low grade glioma, or pLGG, still wreaks plenty of havoc until then, says Sam Blackman, a pediatric oncologist and the co-founder and head of R&D for Day One Biopharmaceuticals.
“Whether it’s the tumor pressing on an optic nerve creating blindness, damage to the hypothalamus or pituitary gland causing profound endocrine disorders, or pressure on motor structures in the brain causing hemiparesis or loss of balance, pLGG is a thief, robbing children of the best parts of their childhood,” Blackman said during a conference call Wednesday.
Though some pLGG tumors can be surgically removed, most patients require a systemic treatment. Chemotherapies and radiation treatment can buy patients time until tumor senescence, but at the cost of severe complications to the body and the brain. Even with these treatments, recurrence of the cancer is common. In those cases, patients haven’t had any additional treatment options. A new drug developed by Day One gives them a new choice.
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The FDA has approved Day One’s tovorafenib for treating children age 6 months and older with pLGG that has either relapsed or has not responded to an earlier treatment. This cancer must have a particular genetic signature, either a BRAF fusion or rearrangement, or a mutation called BRAF V600. Brisbane, California-based Day One will commercialize its new drug under the brand name Ojemda.
Cancer care already has drugs that target BRAF mutations. Like most cancer drugs, they found their first applications in the treatment of adults. One of those BRAF-inhibiting drugs is Novartis’s Tafinlar. The combination of Tafinlar with another Novartis drug, Mekinist, last year expanded its FDA-approved uses to include the treatment of patients age 1 and older with advanced pLGG—but only if the cancer has a BRAF V600E mutation. This mutation is rarer, representing an estimated 10% to 20% of the pLGG patient population, according to Day One. Because Ojemda addresses a broader range of BRAF alterations, including the BRAF V600E mutation covered by the Novartis drug combination, the Day One small molecule can treat more pLGG patients. Ojemda is the first approved systemic therapy for treating pLGG with BRAF rearrangements, including fusions, the FDA said.
Day One studied Ojemda in an open-label Phase 2 clinical trial that enrolled 137 pediatric patients who had a low-grade glioma with a BRAF alteration. The main goal was measuring the overall response rate. The study was designed with two study arms; the FDA decision is based on efficacy results from the 76 patients in arm 1, which showed a 51% overall response rate. The median duration of response was 13.8 months. Arm 2 of the study enabled access to the Day One drug once arm 1 had fully enrolled. Results from the second arm provided additional safety data. The most common adverse reactions reported across both arms included rash, hair color changes, fatigue, viral infection, vomiting, headache, hemorrhage, and fever. Detailed results were published last fall in the journal Nature Medicine.
Ojemda is available as an immediate-release tablet or an oral suspension, both administered once weekly. Dosing of the Day One drug is according to body surface area, which is consistent with dosing for other pediatric medications, Blackman said. Day One has set a $33,816 wholesale price for a 28-day supply. That means the annual cost of the therapy will top $440,000. Ojemda’s price is the same for all packages of the drug and will not change as a child grows and needs higher doses, Chief Commercial Officer Lauren Merendino said.
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The two formulations of Ojemda can be taken at home, which minimizes disruption to the lives of patients and families, Merendino said. Day One’s goal is to establish Ojemda as the physician’s first choice of therapy for pLGG. Merendino said the drug should become available in about two weeks.
Blackman co-founded Day One in 2018 with a focus on developing drugs for pediatric cancers, which he said face an innovation gap compared to the research devoted to treating cancers in adults. The company’s name comes from “the day one talk” physicians have with patients and their families following a cancer diagnosis. Day One procures its drug candidates from other companies. Ojemda was licensed from Takeda Pharmaceutical in 2019.
The FDA decision for Ojemda is an accelerated approval, a speedier path to market for drugs addressing diseases with serious unmet medical need. Day One will need to generate post-marketing clinical data to confirm the safety and efficacy of its new drug. Chief Operating and Financial Officer Charles York said Day One is continuing partnership discussions for Ojemda outside of the U.S., but in the near term, the company’s focus is on U.S. commercialization of the medication, its first FDA-approved product. In its annual report, Day One reported a cash position of $366.3 million at the end of 2023, which the company estimates will be enough to support operations into 2026.
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