3 key tips to set your pediatric program up for success with the RACE for Children Act
by Lynne Georgopoulos, RN, MSHS, RAC, Vice President, Regulatory Strategy at Certara
On August 18, 2020, the Research to Accelerate Cures and Equity (RACE), which amends the Pediatric Research and Equity Act (PREA) comes into effect. With the RACE for Children Act, the FDA is now authorized to require sponsors to submit an agreed initial Pediatric Study Plan (iPSP) with an original NDA or BLA oncology product that may target the growth or progression of a pediatric cancer. New cancer therapies with orphan-designated indications will no longer be exempt from PREA.
The iPSP must include an outline of the planned pediatric investigation(s) and any planned request for deferral or waiver with supporting documentation. According to the guidance by the FDA, a sponsor must submit the iPSP no later than 60 calendar days after the date of the end-of-phase 2 meeting.
What are the important things you need to know about the RACE Act? How can you set up your pediatric program for success?
Learn about the background of the RACE Act and key tips to help guide your strategy and plan.
The pediatric oncology landscape
Cancer is the leading cause of death from disease among children in the United States (US).[1] Each year, approximately 15,000[2] parents will hear the words – “your child has cancer.” Although childhood cancers are rare, the incidence has been steadily increasing from 14.4% in 1980 to 19.2% in 2015 [3]
Leukemias (28%), brain and central nervous system (CNS) tumors (26%), and lymphomas (8%) comprise the majority of pediatric cancers. Surgery, chemotherapy, radiation therapy, and stem cell transplantation are the front-line therapies used to treat these cancers. While these therapies have dramatically improved the overall 5-year survival rate to around 80%, survivorship can come with some significant long-term effects (late effects) in the form of heart and lung damage, infertility, cognitive impairment, growth deficits, hearing loss, and possible development of a secondary cancers later in life.[4]
Significant progress has been made in understanding the genomic landscapes of pediatric cancers.[5] Malignancies occurring in children and adolescents can harbor the same molecular abnormalities as those seen in adults. Therefore, targeted therapies either approved or under development for the treatment of adult cancers, may be effective therapies with less toxic effects, for the treatment of childhood cancers.
Paving the road to foster pediatric drug development
To foster the development and availability of safe and effective medicines for children, two key pieces of legislation in the US were enacted and made permanent in 2012; the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA). BPCA, a voluntary program, provides 6 months of additional marketing exclusivity to sponsors to conduct pediatric studies for medicines that the FDA deems a high priority.[6] PREA, a mandatory program, requires sponsors to conduct pediatric studies under certain circumstances but does not offer incentives.[7] Together, BPCA and PREA have resulted in over 800 products with specific pediatric use information in their label.[8]
Under PREA, the safety and effectiveness (assessment) of a product, for the claimed indication(s) in all relevant pediatric subpopulations (birth up to <17 years of age), must be submitted at the time an application (New Drug Application [NDA], Biologics License Application [BLA] or supplement), for a new active ingredient, new indication, new dosage form, new dosing regimen, or new route of administration is submitted to the Food and Drug Administration (FDA), unless the assessment has been deferred or waived.
PREA requirements rarely apply to cancer drugs because 1) PREA does not apply to orphan-designated indications and 2) if the claimed indication does not occur or rarely occurs in children (eg, lung cancer), the sponsor may request a waiver.
The RACE Act begins on August 18, 2020.
The RACE for Children Act creates a platform to accelerate pediatric cancer therapies by ensuring that new cancer therapies with orphan-designated indications will no longer be exempt from PREA. Furthermore, it gives the FDA authority to require such therapies to be studied in pediatric cancers if the molecular target (mode of action), intended for the treatment of an adult cancer is substantially relevant to the growth or progression of a pediatric cancer.[9]
A sponsor planning to submit an original NDA or BLA on or after August 18, 2020 that is intended for the treatment of an adult cancer, will be subject to PREA as revised under the RACE Act. A sponsor will be required to submit an initial Pediatric Study Plan (iPSP) that will contain an outline of the planned pediatric investigation(s) and any request for deferral or waiver with supporting documentation.
Below are three tips to get ready for the RACE Act
1.Be informed about the RACE Act
- Review relevant FDA guidance on implementing studies of molecularly targeted oncology drugs[10] and FDA guidance on content and process for submitting an iPSP.[11]
- Consult the Relevant Molecular Target list as well as the Non-relevant Molecular Target list. Although these lists will provide some guidance to sponsors to limit regulatory uncertainty, the target list are nonbinding, so each product must be evaluated individually.
- Plan adequately to avoid delays in NDA/BLA filing. It will take 210 days from the time the iPSP is submitted to the FDA to reach agreement on the iPSP or receive a non-agreed letter.
2. Be proactive and be early
- Take advantage of an early advice meeting with the Oncology Center of Excellence Pediatric Oncology Program and select members of the Oncology Subcommittee of the Pediatric Review Committee (PeRC) to seek advice on the development of the iPSP. Meetings will occur within 30 days of receipt of the request. The meeting package should be submitted with the meeting request. The cover letter for these meeting request should clearly state “REQUEST FOR FDARA iPSP MEETING”.[12]
- Avoid unnecessary duplication of studies in children and consider requesting a formal parallel scientific advice with FDA and EMA.[13] Due to the rarity of childhood cancers, international collaboration is essential.
3. Be innovative
- Leverage knowledge from the literature and adults studies to bridge the gap. Model‐informed drug development (MIDD), formally recognized in Prescription Drug User Fee Act (PDUFA) VI, utilizes a wide range of quantitative models to support dose optimization, provide supportive evidence for efficacy, and aid in clinical trial design.[14][15]
- Consider use of real-world data as a means to optimize pediatric drug development in rare disease populations.[16]
- Consider enrollment of adolescents along with adults in Phase 3 trials, if appropriate. In 2019, FDA issued a draft guidance stating that sponsors could enroll adolescents in adult clinical trials after they have obtained pharmacokinetic and toxicity data and if those patients have recurrent cancers or no other treatment option.[17]
Preparing a sound pediatric plan takes a multidisciplinary approach, a clear understanding of the RACE Act, and how best to navigate it to reach your objectives. Certara has extensive experience supporting pediatric programs, providing integrated drug development with regulatory strategy, development of PIPs and PSPs, modeling and simulation with physiologically-based pharmacokinetic (PBPK) modeling, population PK analyses, and more.
Please contact us for a free consultation to see how we can help to accelerate your pediatric program.
To Learn more register for our upcoming webinar: Fostering Pediatric Oncology Drug Development
[1] American Childhood Cancer Organization. US Childhood Cancer Statistics. ASCO website https://www.acco.org/us-childhood-cancer-statistics/, accessed 10 July 2020.
[2] American Childhood Cancer Organization. US Childhood Cancer Statistics. ASCO website https://www.acco.org/us-childhood-cancer-statistics/, accessed 10 July 2020.
[3] Surveillance, Epidemiology, and End Results (SEER) Program. Table 28.2 Age-Adjusted SEER Cancer Incidence Rates, 1975-2015, Ages 0-19. SEER website https://seer.cancer.gov/archive/csr/1975_2015/browse_csr.php?sectionSEL=28&pageSEL=sect_28_table.02#table2, accessed 10 July 2020.
[4] Cancer.net. Late Effects of Childhood Cancer. Approved June 2019. Cancer.net website https://www.cancer.net/navigating-cancer-care/children/late-effects-childhood-cancer, accessed 12 July 2020.
[5] Office of Cancer Genomics. National Cancer Institute. TARGET: Therapeutically Applicable Research to Generate Effective Treatments. Last upated 05 July 2019. Office of Cancer Genomics website https://ocg.cancer.gov/programs/target, accessed 12 July 2020.
[6] FDARA Implementation Guidance for Pediatric Studies of Molecularly Targeted Oncology Drugs: Amendments to Sec. 505B of the FD&C Act, Draft Guidance for Industry, December 2019.
[7] Alyson Karesh, MD, Pediatric and Maternal Health Staff
Office of New Drugs, CDER, FDA website, Pediatric Drug Development: Regulatory Expectations, Office of New Drugs, CDER, FDA, accessed 15 July 2020
[8] Food and Drug Administration. New Pediatric Labeling Information Database. Changes as of March 2019. FDA website https://www.accessdata.fda.gov/scripts/sda/sdNavigation.cfm?sd=labelingdatabase, accessed 12 July 2020.
[9] Food and Drug Administration draft guidance “FDARA Implementation Guidance for Pediatric Studies of Molecularly Targeted Oncology Drugs: Amendments to Sec. 505B of the FD&C Act Guidance for Industry” (December 2019). FDA website https://www.fda.gov/media/133440/download, accessed 10 July 2020.
[10] Food and Drug Administration. FDARA Implementation Guidance for Pediatric Studies of Molecularly Targeted Oncology Drugs: Amendments to Sec. 505B of the FD&C Act Guidance for Industry (December 2019). FDA website https://www.fda.gov/media/133440/download, accessed 13 July 2020.
[11] Food and Drug Administration. Pediatric Study Plans: Content of and Process for Submitting Initial Pediatric Study Plans and Amended Pediatric Study Plans. March 2016. FDA website https://www.fda.gov/media/86340/download, accessed 13 July 2020.
[12] FDA Oncology Center of Excellence, FDA website, June 4, 2020, Pediatric Oncology Product Development Early Advice Meeting (Type F)1, accessed 15 July 2020.
[13] Food and Drug Administration. General Principles EMA_FDA Parallel Scientific Advice (Human Medicinal Products). April 2017. FDA website https://www.fda.gov/media/105211/download, accessed 13 July 2020.
[14] Wang Y, Zhu H, Madbushi R, et al. Model-Informed Drug Development : Current US Regulatory Practice and Future Considerations. Clin Pharmacol Ther. 2019.105;(4):899-911.
[15] Youwei B, LIuJ, Li L, et al. Role of Model-Informed Drug Development in Pediatric Drug Development, Regulatory Evaluation, and Labeling. J Clin Pharmacol. 2019;59(S1):S104-S111.
[16] Food and Drug Administration. Framework for FDA’s Real World Evidence Program. December 2018. FDA website https://www.fda.gov/media/120060/download, accessed 13 July 2020.
[17] Food and Drug Administration. Considerations for the Inclusion of Adolescent Patients in Adult Oncology Clinical Trials Guidance for Industry. March 2019. FDA website, https://www.fda.gov/media/113499/download, accessed 15 July 2020.