The Research to Accelerate Cures and Equity (RACE) for Children Act went into effect on August 18, 2020 and impacts pediatric cancer drug development.
To help sponsors ensure compliance with RACE requirements, our team at the Center for Pediatric Clinical Development (CPCD) answered some FAQs that offer more insight and guidance into the RACE landscape.
What is the RACE Act?
The RACE for Children Act was incorporated as Title V of the FDA Reauthorization Act (FDARA), enacted on August 18, 2017. The RACE Act amended the Pediatric Research Equity Act (PREA) and went into effect on August 18, 2020.
PREA requires that drugs developed for adults need testing in children. PREA allows pediatric study waivers for drugs being developed for adult-related conditions if the condition rarely or never occurs in children. PREA has resulted in new safety and labeling information for some children’s diseases, but not for childhood cancer.
Why not in childhood cancers?
There are two key reasons. First, cancer can originate in different parts of the body in children and adults, even though they can have the same molecular basis. The PREA requirements are only applicable if the indication (tumor type) is the same in both adults and children. For example, a drug developed for adult lung cancer would need to be tested for pediatric lung cancer. Since lung cancer doesn’t occur in children, sponsors would receive a waiver and not be required to study their drug in children.
Second, despite being the leading disease related cause of death for children, pediatric cancer is considered rare (<200,000 patients in the USA). Rare diseases or conditions can receive orphan designation and thus be exempt from PREA requirements.
Since PREA’s enactment in 2003, there has never been an FDA required study under PREA involving a cancer drug—nearly all studies have received waivers or orphan exemption.
Under the RACE Act, new molecularly targeted compounds for adult cancers need to be evaluated for children’s cancers if the molecular target or mechanism of action (MoA) of the drug, not the tumor type or indication, is relevant to the growth or progression of pediatric cancer.
Any new drug application (NDA) or biologics license application (BLA) submitted on or after August 18, 2020 for a new active ingredient must contain reports of molecular targeted pediatric cancer investigations.
Let’s consider the lung cancer example again—the cancer cells in adult lung cancer may use the same process to grow as a cancer that originates in a different part of a child’s body. Because a cancer drug can target a single or small number of these processes (ie its MoA), a drug that can treat an adult’s lung cancer may treat an entirely different type of cancer in children, such as leukemia or brain cancer.
How can sponsors in the oncology space comply with RACE?
Sponsors should familiarize themselves with the list of relevant pediatric molecular targets that the FDA maintains and updates online. Currently, over 200 possible targets are listed and updated continuously.
If a sponsor is developing a drug for an adult cancer, they must have an agreed initial Pediatric Study Plan (iPSP) with the FDA before they can submit their NDA/BLA.
The implementation of RACE poses an additional commitment for many sponsors. They can no longer assume an automatic waiver and must consider their drug product for study in pediatric trials. Sponsors who have never performed pediatric trials will discover that there are many challenges running pediatric compared to adult clinical trials.
Sponsors need to explore different, innovative ways to conduct trials with fewer patients, while limiting costs and considering the use of real world data.
Even if a sponsor’s NDA/BLA submission is expected to occur before the August 18, 2020 cutoff date for RACE, the FDA recommends submission of an agreed iPSP. Depending on the ultimate submission date and if there’s a relevant molecular target for pediatric cancer, an iPSP may be required. Being prepared will help to ensure no additional delays.
How might trials change in the face of RACE?
The way trials are run will likely change significantly. Pediatric cancer patient numbers won’t increase, as it still remains a rare disease (in the USA defined as <200,000 patients). To access as many patients and data as possible, creativity and collaboration will be essential for upcoming trials.
In particular, master protocols, increased collaboration between industry and public partners, and more global trials will be necessary.
Sponsors worldwide will need to align their clinical development to the needs of different countries’ governing bodies, especially if they want to market their drugs overseas. Increased industry and public interaction are necessary for this to work.
What impact will the RACE Act have on bringing treatment options to children?
In the last 20 years, only four cancer treatments were developed and approved specifically for children. In contrast, more than 190 treatments were approved for adults.
The goal of RACE is to accelerate early pediatric evaluation of products and ultimately improve children’s cancer treatments. Clinical care uses the same cancer drugs approved for children from years or even decades ago—no newer therapies have been tested and approved for children. In some cases, such as DIPG (diffuse intrinsic pontine glioma), there are no cures—only minimal therapies offered to prolong life.
The mechanism of action (MoA) of cancer drugs is often “turning off” or slowing the cancer’s growth. The same molecular target can be relevant in different cancers and across different populations. This means it’s likely that the same adult treatments would work in children. But since these treatments are not yet tested or approved for children, most children don’t have access to them.
How can PRA help a sponsor navigate RACE?
The FDA encourages early discussions and will be readily available for conversation as part of the statute. However, with the multitude of changes that RACE brings to oncology trials, speaking with the FDA is only the first step.
Initiating a conversation now with an experienced CRO is paramount. If sponsors want to have an iPSP approved in order to submit an adult study, it is highly recommended that they discuss iPSPs with a CRO.
PRA’s CPCD is in an exciting position to bring innovation and smart design to clinical trials. PRA is prepared to address sponsor needs in the wake of RACE—we even created an inter-departmental team specifically focused on handling pediatric oncology trials. This team includes representatives from multiple facets of our company to ensure all-encompassing solutions.
Collaboration among industry partners is key to the successful implementation of RACE regulations. PRA has extensive experience with pediatric consortia, which will be critical. We also have more than 30 board-certified hematologists/oncologists and more than eight pediatric board-certified hematologists/oncologists.
PRA’s experts are ready to assist sponsors with their pediatric plans. We can help navigate the complexity of this new and exciting era of pediatric research and take pediatric clinical trials to the next level.
Let’s work together to ensure your oncology study complies with the RACE Act.
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RACE Act is significantly changing clinical development. Are you ready?
Our team is here to help you navigate this historic transition in our industry.