Clinical Pharmacology in Drug Development for Rare Diseases in Neurology: Contributions and Opportunities.

Clinical Pharmacology and Therapeutics
Bilal AbuasalMehul Mehta

Abstract

Several challenges are associated with rare disease drug development in neurology. In this article, we summarize the US Food and Drug Administration's experience with clinical drug development for rare neurological diseases and discuss clinical pharmacology's critical contributions to drug development for rare diseases. We used publicly available information to identify and screen drug products approved for rare neurological indications between 1983 and 2019. We highlighted cases in which clinical pharmacology contributed to the evidence of drug efficacy, dose selection for pivotal clinical trials, dose optimization based on intrinsic and extrinsic factors, pharmacokinetic bridging for formulations, and efficacy bridging across different racial groups. Fifty-one approved drug products were identified since the introduction of the Orphan Drug Act in 1983. Interestingly, the number of approvals in the last few years increased significantly, probably due to advances in genomic research and targeted drug modalities. Evaluation of dose selection in patient populations showed that in 52% of cases, the sponsors did not evaluate efficacy for more than one or two dose levels throughout the development program. Clinical pharmacology stud...Continue Reading

References

Oct 3, 2002·Nature Reviews. Drug Discovery·Marlene E HaffnerMarie Moses
Jan 12, 2008·Annual Review of Medicine·Janet Woodcock, Raymond Woosley
Nov 18, 2008·Molecular Genetics and Metabolism·Robert C GriggsUNKNOWN Rare Diseases Clinical Research Network
Nov 13, 2009·Annals of the New York Academy of Sciences·Gráinne C O'KeeffeRoger A Barker
Feb 3, 2011·The Journal of Clinical Investigation·Dinah W Y Sah, Neil Aronin
Jul 18, 2014·Journal of General Internal Medicine·Anne R Pariser, William A Gahl
Mar 15, 2016·AIDS Research and Human Retroviruses·Andrea CalcagnoStefano Bonora
Sep 10, 2016·Clinical Pharmacology and Therapeutics·B P Smith
Aug 18, 2017·American Journal of Medical Genetics. Part a·Lucas KempfRobert Temple
Sep 2, 2017·Nature Reviews. Drug Discovery·Nina L HunterRachel E Sherman
Apr 22, 2019·CPT: Pharmacometrics & Systems Pharmacology·Ayyappa ChaturvedulaNavin Goyal
Dec 1, 2019·Genes·Sandra BrasilAnd Gonçalo Valadão
Feb 18, 2020·Journal of Biopharmaceutical Statistics·Shein-Chung Chow, Zhipeng Huang
Jul 7, 2020·Frontiers in Pharmacology·Zuzanna AngehrnNiedre M Heckman
Dec 29, 2020·Archives de pédiatrie : organe officiel de la Sociéte française de pédiatrie·S Lefebvre, C Sarret

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