Precompetitive Data Sharing as a Catalyst to Address Unmet Needs in Parkinson’s Disease 1

Abstract

Parkinson’s disease is a complex heterogeneous disorder with urgent need for disease-modifying therapies. Progress in successful therapeutic approaches for PD will require an unprecedented level of collaboration. At a workshop hosted by Parkinson’s UK and co-organized by Critical Path Institute’s (C-Path) Coalition Against Major Diseases (CAMD) Consortiums, investigators from industry, academia, government and regulatory agencies agreed on the need for sharing of data to enable future success. Government agencies included EMA, FDA, NINDS/NIH and IMI (Innovative Medicines Initiative). Emerging discoveries in new biomarkers and genetic endophenotypes are contributing to our understanding of the underlying pathophysiology of PD. In parallel there is growing recognition that early intervention will be key for successful treatments aimed at disease modification. At present, there is a lack of a comprehensive understanding of disease progression and the many factors that contribute to disease progression heterogeneity. Novel therapeutic targets and trial designs that incorporate existing and new biomarkers to evaluate drug effects independently and in combination are required. The integration of robust clinical data sets is viewed as a powerful approach to hasten medical discovery and therapies, as is being realized across diverse disease conditions employing big data analytics for healthcare. The application of lessons learned from parallel efforts is critical to identify barriers and enable a viable path forward. A roadmap is presented for a regulatory, academic, industry and advocacy driven integrated initiative that aims to facilitate and streamline new drug trials and registrations in Parkinson’s disease.

Dopamine Transporter Neuroimaging as an Enrichment Biomarker in Early Parkinson's Disease Clinical Trials: A Disease Progression Modeling Analysis

“…Currently, an ongoing CPP consortium project aims to address such issues, envisioning a disease progression model‐based clinical trial enrichment tool. With additional studies at broader stages of PD, and knowledge from previously published UPDRS longitudinal models, CPP will investigate nonlinear models of various levels of complexity to describe the time course of motor scores. The present analysis focused on early motor PD, and the linear progression of the motor scores was adequate for this population given the results of model diagnostics and performance.…”

“…Confirming reduction of DAT density by single‐photon emission computed tomography in subjects with early motor deficit is proposed as a means of enriching future clinical trials of PD therapeutic agents as this facilitates excluding patients who are unlikely to show disease progression in a PD clinical trial. This work was carried out by Critical Path Institute's Critical Path for Parkinson's (CPP) Consortium (funded by Parkinson's United Kingdom) . The CPP's focus is to create new tools and methods that can be applied during the development process of new treatments for PD.…”

Molecular Neuroimaging of the Dopamine Transporter as a Patient Enrichment Biomarker for Clinical Trials for Early Parkinson's Disease

“…There is an urgent need for novel treatments against Parkinson's disease (PD), especially intended to target the earlier stages of disease progression. Clinical trials to evaluate these drug candidates require tools that allow an optimal selection of trial participants, for instance, enrollment of homogeneous populations in terms of their expected disease progression …”

“…Clinical trials to evaluate these drug candidates require tools that allow an optimal selection of trial participants, for instance, enrollment of homogeneous populations in terms of their expected disease progression. 1 The US Food and Drug Administration has approved molecular dopamine transport (DAT) neuroimaging as an adjunct diagnostic evaluation to help differentiate essential tremor from tremor due to parkinsonian syndromes, whereas the European Medicines Agency (EMA) approved DAT imaging to detect loss of functional dopaminergic neuron terminals in the striatum. 2,3 The role of DAT imaging as a drugdevelopment tool (DDT) to optimize predictions of motor progression was recognized as having potential as an enrichment biomarker for clinical trials.…”

“…The CPP working groups developed and executed a comprehensive qualification analysis plan, following the EMA guidance document for the Qualification of Novel Methodologies in Drug Development. The results from the modeling analyses were submitted to the EMA, which led to a qualification opinion for DAT imaging as an enrichment biomarker for 1 Critical Path Institute, Tucson, Arizona, USA; 2 Pfizer, Groton, Connecticut, USA; 3 Merck, Whitehouse Station, New Jersey, USA; 4 Biogen, Cambridge, Massachusetts, USA; 5 clinical trials in early motor PD. 6 The findings were presented via Scientific Advice mechanism with the EMA's Scientific Advice Working (SAWP) Party on July 4, 2017, leading to the Qualification Opinion mechanism with EMA's Committee for Medicinal Products for Human Use (CHMP), on May 28, 2018.…”