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Regulatory environment for novel therapeutic development in mitochondrial diseases
Author(s) -
Hirano Michio,
Berardo Andres,
Barca Emanuele,
Emmanuele Valentina,
Quinzii Catarina,
Simpson Camilla V.,
Engelstad Kristin,
Rosales Xiomara Q.,
Thompson John L. P.
Publication year - 2021
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1002/jimd.12353
Subject(s) - legislation , regulatory science , orphan drug , drug development , european union , regulatory affairs , clinical trial , medicine , pharmaceutical industry , flexibility (engineering) , agency (philosophy) , incentive , disease , intensive care medicine , business , drug , pharmacology , bioinformatics , political science , pathology , public administration , biology , international trade , law , management , philosophy , epistemology , economics , microeconomics
At present, there is just one approved therapy for patients with mitochondrial diseases in Europe, another in Japan, and none in the United States. These facts reveal an important and significant unmet need for approved therapies for these debilitating and often fatal disorders. To fill this need, it is critical for clinicians and drug developers to work closely with regulatory agencies. In the United States, mitochondrial disease patients and clinicians, the United Mitochondrial Disease Foundation, and pharmaceutical industry members have engaged with the Food and Drug Administration to educate each other about these complex and heterogeneous diseases and about regulatory requirements to obtain approvals for novel therapies. Clinical development of therapies for rare diseases has been facilitated by the 1983 US Orphan Drug Act (ODA) and similar legislation in Japan and the European Union. Further legislation and regulatory guidance have expanded and refined regulatory flexibility. While regulatory and financial incentives of the ODA have augmented involvement of pharmaceutical companies, clinicians, with patient advocacy groups and industry, need to conduct natural history studies, develop clinical outcome measures, and identify potential supportive surrogate endpoints predictive of clinical benefit, which together are critical foundations for clinical trials. Thus, the regulatory environment for novel therapeutic development is conducive and offers flexibility for mitochondrial diseases. Nevertheless, flexibility does not mean lower standards, as well‐controlled rigorous clinical trials of high quality are still required to establish the efficacy of potential therapies and to obtain regulatory agency approvals for their commercial use. This process is illustrated through the authors' ongoing efforts to develop therapy for thymidine kinase 2 deficiency.