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

### Background:

As the international community dealt with the ongoing COVID-19 pandemic, important progress continued to be made in the development of new drug-based therapies for the neurodegenerative condition of Parkinson’s disease (PD) in 2021. This progress included both “symptomatic treatments” (ST – improves/reduces symptoms of the condition) and “disease modifying treatments” (DMT - attempts to delay/slow progression by addressing the underlying biology of PD), which can be categorised further based on their mechanisms of action and class of drug.

### Objective:

This report continues previous efforts to provide an overview of the pharmacological therapies - both ST and DMT - in clinical trials for PD during 2021– 2022, with the aim of creating greater awareness and involvement in the clinical trial process. We also hope to stimulate collaboration amongst all stakeholders, including industry, academia, advocacy organizations, and most importantly patient community.

### 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 January 31st 2022. We also assessed active drug development projects that had completed one clinical phase but were yet to start the next.

### Results:

There was a total of 147 clinical trials registered on the ClinicalTrials.gov website as active during the period of analysis. Of these trials, 91 (62%)were investigating STs, while 56 (38%)focused on DMTs. Approximately 1/3 of the studies (34.7%; 51 trials) were in Phase 1, while over half of the trials were in Phase 2 (50.3%; 74 trials). Only 15% (22 trials) of the studies were in Phase 3, of which only 3 trials were evaluating DMTs. Novel therapeutics (42%)were the most common type of agents being tested across all phases of testing, followed by repurposed agents (34%)and reformulations (20%).

### Conclusion:

Despite significant global health constraints, the development of new drug-based therapies for PD continued in 2021. Hopefully with a shift towards a post-pandemic world in which COVID-19 is better managed, we will see an increase in the number of clinical trials focused on drug development for PD. The need for more Phase 3 studies for DMTs remains acute.

## INTRODUCTION

2021 was a remarkable year for medical research, highlighted by the global roll out of rapidly developed vaccines for COVID-19, the WHO recommendation of the first vaccine for malaria [1], clinical evidence of a genetic silencing method for Sickle cell disease [2], and a vastly improved new treatment for hepatitis C [3]. These and many other remarkable scientific milestones were achieved under the considerable constraints and limitations imposed by the ongoing global pandemic. Such successes bode well for future medical progress.

## SUMMARY

Although COVID-19 has represented a significant obstacle during 2021-2022, important progress has still been made in terms of the clinical development of STs and DMTs for PD. The total number of trials and the mix of STs and DMTs has remained similar across the timeframe. While many projects have dropped out of the list, progression to Phase 1 and from Phase 1 to 2 appears to continue. The lack of movement of DMTs from Phase 2 to Phase 3 remains a concern and is a major rate-limiting step to the provision of new therapies to those people living with PD. There are, however, a number of Phase 3 trials in the planning stages and 13 DMT Phase 2 trials due to complete by the end of 2022 (almost two-thirds of the 147 trials in our primary dataset are planned to complete in 2022). This will hopefully result in an increase in the number of DMT Phase 3 trials in the coming years. We look forward to commenting on the outcomes in our future reviews.

## ABBREVIATIONS

AMSC Autologous Mesenchymal stem cells

ASAP Aligning Science Across Parkinson’s

COVID-19 Coronavirus disease 2019

CNS Central Nervous system

CSF Cerebrospinal fluid

DMT Disease Modifying Therapies

FDA Food and Drug Administration

GBA Glucocerebrosidase

GDNF Glial cell-derived neurotrophic factor

GIT Gastrointestinal Tract

GLP-1 R Glucagon-like peptide 1 receptor

ICTRP International Clinical Trials Registry Platform

LD/CD Levodopa and carbidopa

LID Levodopa-induced dyskinesia

LRRK2 Leucine-rich repeat kinase 2

MAMS Multi-Arm Multi-Stage

MAO-B Monoamine oxidase type B

MCI Mild Cognitive Impairment

MOA Mechanisms of Action

MRI Magnetic Resonance Imaging

NIH National Institutes of Health

NINDS National Institute of Neurological Disorders and Stroke

NMDA N-methyl-D-aspartate

NMS Non-motor symptoms

PD Parkinson’s Disease

SC Sub-cutaneous

ST Symptomatic Therapy

UDCA Ursodeoxycholic acid

WHO World Health Organization

## AUTHOR CONTRIBUTION

KMcF, GR, MB, LM, RF, RKW & SRWS performed the trial categorization & helped write/edit the manuscript.

## ACKNOWLEDGMENTS

The authors would like to thank Prof Tanya Simuni of Northwestern University and Helen Matthews of Cure Parkinson’s for reading the manuscript and providing constructive feedback. The authors would also like to thank all of the trial participants and their families, and the researchers involved in the ongoing clinical research for PD.

## CONFLICT OF INTEREST

The authors declare no conflicts of interest.

## SUPPLEMENTARY MATERIAL

[1] The supplementary material is available in the electronic version of this article: https://dx.doi.org/10.3233/JPD-229002.

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