Day One Bio Aims To Shorten The Time Gap On Cancer Treatments For Kids
By Ben Comer, Chief Editor, Life Science Leader
One of the biggest incentives for developing new therapies for rare pediatric cancers is the FDA’s rare pediatric disease Priority Review Voucher (PRV) program. If a drug in development meets the criteria for a PRV, the sponsor company, upon FDA approval, receives a PRV that can be redeemed for FDA priority review of a different pipeline product, or can be sold to another company. Over the past several years, the average going price for a PRV has hovered around $100 million, with no strings attached.
Day One Bio, a company focused on speeding up the development and approval of oncology drugs for pediatric patients, sold its PRV for $108 million in May 2024. The company received the PRV upon approval of Ojemda, a treatment indicated for patients six months of age and older with relapsed or refractory pediatric low-grade glioma (pLGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation.
Historically, there have been good economic reasons to support focusing on adult populations first in oncology: larger patient populations that make it easier to conduct trials, and a bigger commercial potential, says Bender. Traditionally, as an adult oncology clinical program progresses into later stages of development, a company will begin to consider pediatric studies. “What we do is the opposite of that … we’re trying to accomplish a phase shift,” he says.
Pediatrics First
With Ojemda, Day One in-licensed the drug from Takeda, which had already “done a lot of work in adults, including establishing a dose, doing combination work, and evaluating the drug in melanoma in a small number of patients,” which established a baseline set of clinical data that was accessible, says Bender. In parallel, researchers at Dana Farber Cancer Center had engaged Takeda in providing drug supply for investigator-sponsored studies in pediatric brain tumors.
By the time Day One in-licensed the drug from Takeda, Dana Farber had produced early data on nine pediatric patients, in addition to Takeda’s data in an adult population, which helped to de-risk Day One’s development plans. “That allowed us to go straight into what turned into a registrational trial for pLGG,” says Bender. Day One is currently conducting a Phase 3 trial with Ojemda for a second pLLG indication — frontline RAF-altered pLLG — although the PRV program stipulates that the same active ingredient is not eligible for more than one PRV.
Day One also has in-licensed an ADC therapy, currently in early clinical development, from China-based MabCare Therapeutics. That candidate targets PTK7, which is expressed in a diverse range of both adult solid tumors as well as a few pediatric solid tumors, says Bender. “The pediatric tumors are osteosarcoma, neuroblastoma, rhabdomyosarcoma, and potentially others … we’re going to do some work to determine exactly where PTK7 is expressed, and that's the basis on which we'll select patients and develop.” Because the ADC from MabCare had not been tested in patients prior to Day One’s initial clinical research, “we have to do the work in adults just to establish a baseline safety profile.”
Once the company has collected enough safety information, it will communicate with the FDA about moving to a pediatric Phase 1 dose confirmation study as soon as possible. “We’ll see where we go in the pediatric space relative to the adult space — both are high priorities for us — and that is a typical path, it’s just that pediatric studies will happen much earlier than it does at other companies.”
Could Day One’s ADC candidate targeting PTK7 in pediatric cancer eventually land the company a second PRV? “I think the tumors that express PTK7 in the pediatric setting would definitely meet those qualifications … if we pursue it and it’s approved first in one of those pediatric settings, we would be granted a PRV, assuming the legislation is reauthorized.”
Priority Review Voucher Program Status
Making assumptions about federal health policy at this moment in time is a fool’s errand, due to the unsettled status of incoming Trump administration health officials currently going through the Congressional confirmation process. The PRV program was not reauthorized amid government funding negotiations at the end of 2024, and hit its sunset date on December 20.
Legislation to reauthorize the program was initially included in the end-of-year budget bill but was stripped out prior to passage. Alexander Gaffney, executive director, regulatory policy and intelligence at Politico’s AgencyIQ unit — who publishes a free and excellent daily newsletter on FDA activities — told me that despite the expiration of the program, existing vouchers are still able to be redeemed, and that the PRV program will still be able to award vouchers to companies that already had obtained Rare Pediatric Disease designation from the FDA prior to the December 20, 2024 expiration.
Advocates are expected to continue pushing Congress for program reauthorization at the earliest opportunity, but they may have to wait until later in the year, Gaffney predicted.