Throughout 2020, the CPCD led an effort to ensure the industry prepared for the impact the Research to Accelerate Equity and Cures (RACE) for Children Act would have on oncology drug development once it went into effect on August 18th, 2020. Late last year, the CPCD hosted a webinar with Xtalks to update the industry on the impact this legislation has had thus far and how the industry has adapted to meet the requirements of the legislation.
Late last year, the CPCD hosted a webinar with Xtalks to update the industry on the impact the RACE Act legislation has had thus far. Read on for a summary of the webinar and find out how industry has adapted to meet the requirements of the legislation.
Historically, treatment options for children with oncology diagnoses have long been understudied, leaving children to be treated off-label with medications only assessed for safety and efficacy in adults. The RACE for Children Act amends the FDA’s existing Pediatric Research and Equity Act (PREA), requiring evaluation of new molecularly targeted drugs and biologics “intended for the treatments of adult cancers and directed at a molecular target substantially relevant to the growth or progression of a pediatric cancer.” It also eliminates the orphan exemption from PREA for cancer drugs directed at relevant molecular targets.
Dr. Gregory Reaman, Associate Director of Pediatric Oncology in the FDA’s Oncology Center of Excellence, explained: “The purpose here is to accelerate initial pediatric evaluations of appropriate agents in development in timeline and not necessarily increase the number of pediatric phase I studies.”
Overall, for FDA-approved cancer drugs, there has been a median lag of 6.5 years between the first clinical trial in adults (first-in-human) to the first-in-child trial. With the RACE for Children Act, development can no longer be delayed as long for certain molecular targets. Sponsors could be precluded from submitting an NDA/BLA until they have an agreed upon initial Pediatric Study Plan (iPSP).
In the first five months, Dr. Reaman and the FDA reviewed 151 agreed iPSPs and 113 full waivers—with 2 deferrals, 5 partial waivers, and 14 receiving partial waivers and deferrals. Dr. Reaman said, “There is no question that these amendments to PREA by the RACE for Children Act are finally going to bring equity to children with cancer, and hopefully globally.”
While a US regulation, the global impact of the RACE for Children Act will be driven by collaboration between stakeholders. Prof. Gilles Vassal, Head of Pediatric Research Program at Gustave Roussy/University Paris-Saclay is a vocal advocate for collaboration, chairing ACCELERATE, an international stakeholder platform driving innovation in pediatric oncology. He highlighted the long development timeline after adult approvals have been exacerbated by the previous granting of waivers based on cancer type, not the mechanism of action. Research shows that in 98% of cases, the adult medications are relevant to children.
Prof. Vassal called for strong biological databases of genome sequencing to determine if a drug is relevant to a pediatric disease: “There is a real opportunity to make it right for children, and there is a real need to work together.” He encouraged early pipeline discussions between scientists, pediatric oncologists, and pharma to ensure biological data are generated in phase I that would determine if a compound is relevant to pediatric discussions. In addition, he emphasized the need for easy access to data and high-quality clinical trial platforms, as well as international agreement on required biological and preclinical data. Working together with all stakeholders, i.e., academia, industry, parents, and regulatory bodies will help prioritize which drugs should move forward.
Dr. Anjali Sharma, Pediatric Oncology Development Lead and Early Oncology Development Lead at Amgen, spoke to the value collaboration has brought them. Engaging with investigators and regulators early has helped determine how they now evaluate their pipeline assets. She agreed with Prof. Vassal that early pipeline discussions are integral to pediatric planning: “It used to happen that a thought of a pediatric study plan really occurred at First-in-Human. Now, thanks to the RACE for Children Act, the needle has now moved backwards: we begin thinking about a pediatric plan back in discovery and screening to see what the molecule is, how the molecule acts, and how it can be translated into a pediatric tumor.”
This early consideration has helped the product teams to understand the pediatric potential early on in consideration of the adult potential, allowing for a holistic development plan. Late optimization is when Amgen really looks to understand the molecular characteristics in adult models and truly starts the pediatric assessment.
Dr. Sharma said it is a challenge to understand how to assess these molecules with primarily adult indications in pediatric specific indications. Considering early means we can engage with FDA and EMA early, driving advancements of pediatric treatment options on a global scale.
The potential for radical treatment improvement by considering mechanism of action was showcased by the personal story Dr. Beth Anne Baber, Founder & President, TigoHealth. Her son, Conor, was diagnosed at 16 months old with high-risk neuroblastoma. As scientists, Dr. Baber and her husband looked into the molecular makeup of his tumor, realizing the markers he had were negative for aggressive disease—despite the histology indicating it was aggressive. Deciding to follow what they saw, they decreased the amount of treatment to match his markers and made all future decisions for his therapy in accordance with the markers. “As scientists, it was not very easy to do for a child. But as scientists, it was what we felt the most comfortable doing,” said Dr. Baber. There was soon no evidence of disease. Now aged 16, Conor is healthy and enjoying his life. Inspired by their family’s approach to Conor’s treatment, Dr. Baber has moved into industry to work to use venture-philanthropy to drive medical advancements.
Conor’s cancer journey is unique—it was driven by qualified parents who were able to tailor a treatment option to the needs of his specific tumor. As stakeholders continue to push for the advancement of treatment options for children, legislation such as the RACE for Children Act provides important steps to safe and proven treatment options. The global impact of this legislation will require collaboration across industry, academia, regulators, and patients. We’d like to thank our speakers for making this webinar possible.Click here to hear the full webinar. Read our two-part whitepaper series to learn more about how global collaboration will assist with meeting RACE Act requirements.
Our industry is still guessing the clinical needs of children by settling for a fraction of what works in adults. We’re changing that.
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