The Research to Accelerate Cures and Equity Act led to an increase in required pediatric studies for recently approved cancer therapies within the first year of the act’s implementation, according to study results.
Researchers presented the findings during American Association for Cancer Research Annual Meeting.
Rationale and methods
“Significant progress has been made in cancer care and treatment, with many novel therapeutics recently approved. Many of these exciting advancements, however, have not easily translated to new treatment options and approvals for pediatric oncology patients,” Brittany Avin McKelvey, PhD, science policy analyst with Friends of Cancer Research, told Healio. “To encourage study of therapeutics to treat pediatric cancers, many legislative efforts have been made, including the 2017 passage of the Research to Accelerate Cures and Equity [RACE] Act, which was implemented in August 2020. It is important to assess the impact of the RACE Act on pediatric study requirements and pediatric oncology drug development, as well as identify whether additional policy opportunities exist to maximize its impact.”
To do so, McKelvey and colleagues evaluated all new FDA-approved oncology drug applications or biologics license applications between 2019 and 2021, stratifying qualifying drugs by applications approved 1 year before and 1 year after RACE implementation.
Key findings
Researchers identified 19 therapeutics within the study period, of which 63.2% received approval before implementation of the RACE Act and 36.8% after.
Results showed only 11.8% of therapeutics approved had indications for pediatric use at the time of initial drug application. Among them, 78.9% of approved applications received an orphan drug designation.
Before initiation of the RACE Act, 91.7% of therapies approved had a relevant mechanism of action that could have required pediatric study had the drug application been submitted after implementation of the act, according to the researchers. After implementation of the act, 71.4% of cancer therapies received an orphan drug designation, of which 60% required pediatric assessment because of the relevancy of the mechanism of action.
Before implementation of the RACE Act, pediatric clinical trials were waived or exempt for all therapies, whereas after implementation of the act, 42.9% of approved cancer therapies required pediatric research.
“We found a significant increase in required pediatric studies for new oncology therapeutics after implementation of the RACE Act, with the largest effect seen in orphan-designated therapeutics that are no longer automatically exempt,” McKelvey said. “However, many pediatric study requirements are still waived for therapeutics with a relevant mechanism of action to pediatric cancers, highlighting the need for additional opportunities to facilitate and encourage robust pediatric studies.”
Implications
Trends are emerging on the RACE Act’s effectiveness in increasing pediatric study of oncology therapeutics, which could eventually translate into new lifesaving treatment options for children with cancer, McKelvey said.
“All pediatric studies required were deferred,” she said. “Many of these studies require data completion in a long timeframe, for example in 2028. Therefore, we still have many years until we will be able to see if the required pediatric studies lead to actionable data that can support labeling modifications and inclusion of information to inform appropriate use in pediatric patients.”
The researchers plan to expand their initial analysis beyond the first year of RACE Act implementation.
“We were only able to evaluate the requirements of pediatric study, and we cannot currently assess the completion of the studies and whether they lead to improved pediatric labeling,” McKelvey said. “We hope by accruing additional data we can continue to assess the impact of current policy and assess additional opportunities to facilitate and encourage pediatric study.”
Although pediatric study of cancer drugs has increased, many requirements are still waived for therapeutics with a relevant mechanism of action, McKelvey said.
“[That is] due to studies being deemed ‘impossible or impracticable’ due to the prevalence of the mutation or cancer type in the pediatric population,” she added. “Due to the rare prevalence of pediatric cancers, and the further bucketing of patients by specific alterations, the issue of prevalence is not uncommon.”
According to McKelvey, rare target patient populations may require innovative trial designs, such as platform studies or adaptive trial designs, and collaboration to make possible the impossible or impracticable studies.
“Further, there is opportunity to leverage the data and experience from the adult clinical trials to inform and expedite pediatric drug development by extrapolating certain safety and efficacy data,” she said. “There may also be an opportunity to expand the eligibility criteria to enable enrollment of adolescents in the premarket, pivotal registrational trial, to provide important information on the safety and efficacy in this population sooner.”
Ongoing investigation is essential, according to moderator Louis M. Weiner, MD, director of Georgetown Lombardi Comprehensive Cancer Center.
“Early results show The RACE Act is having a desired impact, making it important for these drugs to be evaluated in pediatric populations, but it is a long time frame,” he said. “The assumption is that having more access early on will ultimately be beneficial, but it is important to study the actual impact.”
