New Drugs for Parkinson's Disease: The Regulatory and Clinical Development Pathways in the United States
New Drugs for Parkinson's Disease: The Regulatory and Clinical Development Pathways in the United States
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DOI：
10.1002/mds.27220
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发表时间：
2018-06-01
影响因子：
8.6
通讯作者：
Olanow, C. Warren
中科院分区：
文献类型：
--
作者：
Kieburtz, Karl;Katz, Russell;Olanow, C. Warren
The past several years have seen an explosion in the number of candidate therapies for Parkinson’s disease (PD). These include new formulations and routes of delivery of dopaminergic agents aimed at reducing off time and dyskinesia, rescue therapies designed to provide rapid and predictable treatment of individual off episodes, therapies for the nonmotor features of PD, and novel approaches targeting factors implicated in the etiopathogenesis of PD, such as inflammation, glucocerebrosidase (GBA), leucine-rich repeat kinase 2 (LRRK2), and alpha-synuclein. While these strategies have the potential to meaningfully affect the course of the disease and the quality of life for patients with PD, none can be made commercially available to the general public until they are approved for use by regulatory authorities. Most movement disorder specialists are familiar with the laboratory studies and clinical trial methodology necessary to develop and evaluate these new compounds, but most are not familiar with the regulatory requirements for drug approval. Currently, the average cost and time of central nervous system drug development are approximately $1.3 billion and 13 years, respectively, which has limited the interest of many companies from pursuing new therapies in this space. Knowledge of the regulatory process may help to reduce these costs and timelines, and encourage biotech and big pharma companies to be willing to invest in new drugs for PD. In this review, we will describe the key elements of the regulatory process with a particular focus on the methodology applicable to the US Food and Drug Administration (FDA) in the United States. Patients in the United States as well as in Europe, Japan, and Canada are served by the FDA, the European Medicines Agency (EMA), the Pharmaceuticals and Medical Devices Agency, and Health Canada, respectively. These agencies share common principles promulgated under the International Conference for Harmonization guidelines, which are focused on ensuring a clear delineation of the safety, efficacy, and risk/benefit of proposed products. There are, however, important regional differences. For example, individual country authorities within European Union (EU) member states make independent decisions about marketing authorization and pricing, whereas the FDA regulates drugs in all 50 states, but is not involved in pricing decisions. The FDA typically demands two well-controlled and adequate (doubleblind) studies for approval. The EMA typically requires comparator studies as well, where safety and efficacy of a proposed new product is compared to an approved treatment to aid in decisions regarding approval and pricing, but such studies are not required in the United States or Canada. Japanese authorities require that new products be specifically tested in Japanese patients before approval, whereas the FDA and EMA may accept high-quality, well-controlled studies wherever they are performed. Approval in one regulatory region does not assure approval in another. A better appreciation of these regulatory pathways and requirements by scientists, clinical investigators, and the pharmaceutical industry will likely help reduce the cost and time of drug development, and speed the approval process.
