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Regulatory strategies for rare diseasesunder current global regulatory statutes: adiscussion with stakeholders

Mulberget al. Orphanet Journal of Rare Diseases - 2019

Rare or orphan diseases often are inherited and overwhelmingly affect children. Many of these diseases have notreatments, are incurable, and have a devastating impact on patients and their families. Regulatory standards fordrug approval for rare diseases must ensure that patients receive safe and efficacious treatments. However, regulatorybodies have shown flexibility in applying these standards to drug development in rare diseases, given the uniquechallenges that hinder efficient and effective traditional clinical trials, including low patient numbers, limited understandingof disease pathology and progression, variability in disease presentation, and a lack of established endpoints.To take steps toward improving rare disease clinical development strategies under current global regulatory statutes,Amicus Therapeutics, Inc. and BioNJ convened a 1-day meeting that included representatives from the Food and DrugAdministration (FDA), biopharmaceutical industry, and not-for-profit agencies. The meeting focused on orphan diseases inpediatric and adult patients and was intended to identify potential strategies to overcome regulatory hurdles throughopen collaboration.During this meeting, several strategies were identified to minimize the limitationsassociated with low patient numbers inrare diseases, including the use of natural history to generate historical control data in comparisons, simulations, andidentifying inclusion/exclusion criteria and appropriate endpoints. Novel approaches to clinical trial design were discussedto minimize patient exposure to placebo and to reduce the numbers of patients and clinical trials needed for providingsubstantial evidence. Novel statistical analysis approacheswere also discussed to address the inherent challenges of smallpatient numbers. Areas of urgent unmet need were identified, including the need to develop registries that protectpatient identities, to establish close collaboration and communication between the sponsor and regulatory bodies toaddress methodological and statistical challenges, to collaborate in pre-competitive opportunities within multiple sponsorsand in conjunction with academia and disease-specific patient advocacy groups for optimal data sharing, and to developharmonized guidelines for data extrapolation from source to target pediatric populations. Ultimately, these innovations willhelp in solving many regulatory challenges in rare disease drug development and encourage the availability of newtreatments for patients with rare diseases.