Objective: This presentation focuses on neuroimaging of the Dopamine Transporter as an enrichment biomarker in clinical trials of Parkinson’s disease (PD).

Background: The Critical Path for Parkinson’s (CPP) Consortium is a new global public private partnership focused on regulatory science. The aim of CPP is to target early stages of PD with the goal of advancing treatments that hold promises for delayed disease progression. Imaging of dopamine transporter (DAT) density represents a viable biomarker to enable identification of a target patient population for enrichment in therapeutic trials.

Methods: A defined regulatory submissions strategy was undertaken with the U. S. Food & Drug Administration (FDA) and European Medicines Agency (EMA) through the formal biomarker qualification process. The path included a comprehensive literature review, proposed analysis plan of both observational and clinical trial data and assessment of biomarker reproducibility and reliability.

Results: The literature review, preliminary data and presented analysis plan for the use of DAT imaging in PD clinical trials was reviewed by regulatory authorities through the formal biomarker qualification program. The FDA issued a publically posted formal letter of support in March 2015 that identified their support for the use of DAT neuroimaging as an exploratory prognostic biomarker for identification of patients for enrollment in PD clinical trials; (EMA plans to issue a similar letter of support in 2016).

Conclusions: It is proposed that the use of DAT neuroimaging as an enrichment biomarker will facilitate enrollment of cohorts of subjects with reduced variability into clinical trials. Application of the proposed biomarker will improve statistical power and reduce exposure of individuals unlikely to have PD to risks associated with clinical trials from which they are unlikely to benefit. Qualification for the use of DAT in PD clinical trials has applications across multiple drug candidates, independent of mechanism of action or sponsor, and will serve to improve the chance of successful clinical trials in a target population that holds most promise for treatment response. FDA letter of support: http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/UCM439715.pdf

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MDS Abstracts - https://www.mdsabstracts.org/abstract/critical-path-for-parkinsons-ii-global-regulatory-agencies-support-the-use-of-dopamine-transporter-neuroimaging-as-an-enrichment-biomarker-to-enable-clinical-trials-in-early-parkinsons-disease/