A peculiarity of the most common form of brain cancer in children is that the tumors eventually stop growing as the child gets older. The reasons for this tumor aging are not yet fully understood, but pediatric low-grade glioma (pLGG) is still wreaking havoc until then, says Sam Blackman, a pediatric oncologist and co-founder and head of research and development at Day One Biopharmaceuticals.
“Whether it is a tumor pressing on an optic nerve causing blindness, damage to the hypothalamus or pituitary gland causing serious endocrine disruption, or pressure on motor structures in the brain causing hemiparesis or loss of balance, pLGG is a Thief who robs children of the best parts of their childhood,” Blackman said during a conference call Wednesday.
Although some pLGG tumors can be removed surgically, most patients require systemic treatment. Chemotherapy and radiation treatments can give patients time for the tumor to age, but at the cost of serious complications for the body and brain. Despite these treatments, cancer recurrence often occurs. In these cases, patients had no additional treatment options. A new drug developed by Day One gives them a new choice.
The FDA approved Day One’s tovorafenib for the treatment of children 6 months of age and older with pLGG who have either relapsed or failed to respond to previous treatment. This cancer must have a specific genetic signature, either a BRAF fusion or rearrangement or a mutation called BRAF V600. Day One, based in Brisbane, California, will market its new drug under the brand name Ojemda.
There are already drugs in cancer treatment that target BRAF mutations. Like most cancer drugs, they found their first applications in the treatment of adults. One of these BRAF-inhibiting drugs is Tafinlar from Novartis. Combining Tafinlar with another Novartis drug, Mekinist, last year expanded its FDA-approved uses to include treating patients aged 1 year and older with advanced pLGG – but only if the cancer has a BRAF V600E mutation. This mutation is rarer, accounting for an estimated 10 to 20% of the pLGG patient population, according to Day One. Because Ojemda targets a broader range of BRAF alterations, including the BRAF V600E mutation covered by Novartis’ drug combination, the Day One small molecule can treat more pLGG patients. According to the FDA, Ojemda is the first approved systemic therapy to treat pLGG with BRAF rearrangements, including fusions.
Day One studied Ojemda in a Phase 2 open-label clinical trial involving 137 pediatric patients who had low-grade glioma with a BRAF alteration. The main objective was to measure the overall response rate. The study was designed with two study arms; The FDA’s decision is based on efficacy results from the 76 patients in Arm 1, which showed an overall response rate of 51%. The median duration of response was 13.8 months. Arm 2 of the study provided access to day one drug once Arm 1 was fully enrolled. Results from the second arm provided additional safety data. The most common side effects reported in both arms included rash, hair color changes, fatigue, viral infection, vomiting, headache, bleeding and fever. Detailed results were published last fall in the journal Nature Medicine.
Ojemda is available as an immediate-release tablet or oral suspension, each administered once weekly. Dosing of the Day One drug is based on body surface area, which is consistent with dosing of other pediatric medications, Blackman said. Day One has set a wholesale price of $33,816 for a 28-day supply. This means the annual cost of therapy will exceed $440,000. Ojemda’s price is the same for all packs of the drug and does not change as a child grows and requires higher doses, said Lauren Merendino, chief commercial officer.
Ojemda’s two formulations can be taken at home, minimizing disruption to the lives of patients and families, Merendino said. Day One’s goal is to establish Ojemda as the first-choice therapy for physicians at pLGG. Merendino said the drug should be available in about two weeks.
Blackman co-founded Day One in 2018 with a focus on developing medicines for childhood cancers, where he says there is an innovation gap compared to research into treating adult cancers. The company’s name comes from the “Day 1 conversation” that doctors have with patients and their families after a cancer diagnosis. Day One sources its drug candidates from other companies. Ojemda was licensed by Takeda Pharmaceutical in 2019.
The FDA’s decision for Ojemda provides accelerated approval and a faster path to market for medicines to treat diseases with significant unmet medical needs. Day One needs to generate post-marketing clinical data to confirm the safety and effectiveness of its new drug. Charles York, chief operating and financial officer, said Day One is continuing partnership discussions for Ojemda outside the U.S., but the company’s near-term focus is on commercializing the drug, its first FDA-approved product, in the U.S.
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