- The Relevant Molecular Target List and The Non-Relevant Molecular Target Leading to Waiver List
- Common Commentary for EMA and FDA Scientific Review of Pediatric Cancer Drug Development Plans
The mission of the Oncology Center of Excellence Pediatric Oncology Program is to promote the development of safe and effective new drugs and biologics to treat cancer in children. To do this, we attempt to maximize the authority available through the Best Pharmaceuticals for Children Act (BPCA) to increase the number of Written Requests for pediatric studies of appropriate new drugs developed for adult cancers much earlier in the development timeline.
Recent amendments (FDARA 2017) to the Pediatric Research Equity Act (PREA) provide enhanced opportunities to extend the promise of precision medicine to children with cancer. The FDA, with input from the National Cancer Institute and the pediatric cancer research community, developed a Pediatric Molecular Target List to comply with the amended provisions of PREA to provide some guidance to industry in planning for new drug and biologic submissions.
The Pediatric Oncology Program holds Pediatric Oncology Product Development Early Advice Meetings with sponsors to discuss pediatric development plans. We also hold various meetings with stakeholders, including the Pediatric Subcommittee of the Oncologic Drugs Advisory Committee, the Oncology Subcommittee of the Pediatric Review Committee (PeRC), as well as other public outreach meetings.
These lists include 1) molecular targets for which there is evidence and/or biologic rationale (gene expression data, genetic alterations, non-clinical or clinical data obtained from publicly available databases and/or peer-reviewed publications) to suggest their potential relevance to the growth or progression of one or more pediatric cancers and 2) molecular targets for which there is evidence as noted above that indicates that they are not associated with the growth or progression of pediatric tumors, and for which requirement for early pediatric assessment of drugs and biologics directed at these targets could be waived. Since their original establishment and publication in 2018, the lists were converted into a spreadsheet format to facilitate computability and reduce duplication. The use of accepted gene nomenclature or simplified descriptors was adopted to describe targets of interest. Also, additional molecular targets were included in the Relevant Molecular Target and in the Non-Relevant Molecular Target Leading to Waiver Lists. These lists will be regularly updated as new information becomes available.
These lists fulfill the statutory requirements imposed by FDARA and are expected to provide some guidance to industry in planning for initial Pediatric Study Plan submissions for new drug and/or biologic products in development for cancer in accordance with the amended provisions of the Pediatric Research Equity Act. The absence of a molecular target to which a specific drug is directed from the Relevant Molecular Target List does not mean a clinical evaluation of the drug in the pediatric population will not be required. As well, the presence of a target on the Relevant Molecular Target List in itself does not automatically constitute a requirement for a clinical study (FDARA Implementation Guidance for Industry on Pediatric Studies of Molecularly Targeted Oncology Drugs).
- The Relevant Molecular Target List (XLSX, 68KB)
- The Non-Relevant Molecular Target Leading to Waiver List (XLSX, 16KB)
The evolving regulatory landscape surrounding pediatric cancer drug development in the U.S. and EU has more closely aligned the timelines for required submission of plans for pediatric development of appropriate new cancer drugs and biologics developed for adults with cancer. This has created an opportunity for sponsors to seek preliminary scientific advice from both the EMA and the FDA on Pediatric Investigation Plans (PIPs) and initial Pediatric Study Plans (iPSPs) through the Pediatric Cluster Calls coordinated by the FDA’s Office of Pediatric Therapeutics.
Given the global nature of cancer drug development and the relative rarity of childhood cancer, which impacts study populations for clinical trials, the demand for international collaboration in study design and conduct has intensified. We have recommended that new PIPs and iPSPs for new cancer products be submitted to their respective agencies simultaneously to promote global coordination and international research collaboration (Reaman et al. J Clin Oncology, 2020).
This Common Commentary template is provided to demonstrate to sponsors the structure of our scientific discussions and review in the context of regulatory agency positions on selected aspects of pediatric drug development.