Parkinson’s Disease Drug Therapies in the Clinical Trial Pipeline: 2021 Update

Abstract

Background: Despite the COVID-19 pandemic, there has been considerable activity in the clinical development of novel and improved drug-based therapies for the neurodegenerative condition of Parkinson’s disease (PD) during 2020. The agents that were investigated can be divided into “symptomatic” (alleviating the features of the condition) and “disease modifying” (attempting to address the underlying biology of PD) treatments, ST and DMT respectively, with further categorisation possible based on mechanism of action and class of therapy. Objective: Our goal in this report was to provide an overview of the pharmacological therapies –both ST and DMT - in clinical trials for PD during 2020–2021, with the aim of creating greater awareness and involvement in the clinical trial process. We also hope to stimulate collaboration amongst commercial and academic researchers as well as between the research and patient communities. Methods: We conducted a review of clinical trials of drug therapies for PD using trial data obtained from the ClinicalTrials.gov and World Health Organisation (WHO) registries, and performed a breakdown analysis of studies that were active as of February 18th 2021. We also assessed active drug development projects that had completed one clinical phase but were yet to start the next. Results: We identified 142 trials on ClinicalTrials.gov and 14 studies on the WHO registries that met our analysis criteria. Of these 156 trials, 91 were ST and 65 were DMT, Of the 145 trials registered on ClinicalTrials.gov in our 2020 analysis, 45 fell off the list and 42 were added. Despite this change, the balance of ST to DMT; the distribution across phases; the profile of therapeutic categories; and the proportion of repurposed therapies (33.5%); all remained very similar. There are only two DMTs in phase 3, and we identified 33 in-between-phase projects. Conclusions: Despite the effects of the coronavirus pandemic, investment and effort in clinical trials for PD appears to remain strong. There has been little change in the profile of the clinical trial landscape even though, over the past year, there has been considerable change to the content of the list.

Parkinson’s Disease Drug Therapies in the Clinical Trial Pipeline: 2022 Update

“…The methods employed in this report were identical to those we have used previously [ 10 ]. Briefly, clinical trial data was downloaded from the ClinicalTrials.gov and WHO registries on the 31 st January 2022, based on the following search criteria: Condition: Parkinson; Parkinson’s Study type: Interventional Phase: Early Phase 1, Phase 1, Phase 2, Phase 3 Status parameter: “Recruiting”, “Not yet recruiting”, “Active, not recruiting”, or “Enrolling by invitation”.…”

Evidence for Oxidative Pathways in the Pathogenesis of PD: Are Antioxidants Candidate Drugs to Ameliorate Disease Progression?

“…This suggests that bioactive vitamin E analogs with antioxidative and anti-inflammatory activities may be neuroprotective and should be tested further for efficacy in PD. Tocotrienol-rich vitamin E (Tocovid) possesses potent antioxidant and anti-inflammatory properties and is currently in clinical trials for PD (NCT04491383) [129].…”

Can Innovative Trial Designs in Orphan Diseases Drive Advancement of Treatments for Common Neurological Diseases?

“…Such advances have catalyzed investments from the biotech community and led to a rich expansion of research that includes early intervention stratified by genetic status in at‐risk individuals 42 . Encouragingly, the PD pipeline has remained strong despite the global COVID‐19 pandemic 43 . The outlook for effective PD therapeutics is tempered by an extraordinarily high failure rate of PD trials, particularly for those that target disease modification 44 .…”

“… 42 Encouragingly, the PD pipeline has remained strong despite the global COVID‐19 pandemic. 43 The outlook for effective PD therapeutics is tempered by an extraordinarily high failure rate of PD trials, particularly for those that target disease modification. 44 A variety of reasons have been proposed, including lack of translational validity of preclinical models, failure of agent to reach and engage target adequately, unknown mechanisms of action for many candidates, confounding of currently approved symptomatic therapy, and absence of objective measures of true disease progression.…”