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

Abstract

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.

A New Chapter for the Journal of Parkinson’s Disease

“…The Journal of Parkinson's Disease is nimble and open to collaboration which provides many opportunities for innovative and impactful content that we will continue to nurture. We already mentioned our collaboration with Cure Parkinson's and Parkinson's research advocates to produce the Clinical Trial Pipeline series [1][2][3]. We intend to further develop and expand our collaboration with the Michael J.…”

Defining the unknowns for cell therapies in Parkinson's disease

“…For PD, there are already a range of advanced therapies specifically targeted at later stages of the disease, including deep brain stimulation, intrajejunal infusion of duodopa ( Box 1 ) and continuous subcutaneous delivery of apomorphine. We direct readers to Jankovic and Tan (2020) , McFarthing et al (2022) and Stoker and Barker (2020) for comprehensive reviews of current and future treatments for PD. The role of cell transplantation in this therapeutic landscape, how and when it will be best suited as an intervention, and the readiness of the patient population for such an intervention are currently unclear.…”

“…Looking ahead, it will be important to refine the clinical trial parameters, and collaboration between all stakeholders – patients, healthcare providers, graft tissue developers and regulators – will be needed to ensure successful implementation of cell transplantation therapies for PD. The future landscape will also depend on the success of other disease-modifying interventions that tackle some of the possible root causes of the disease, many of which are also being trialled currently ( McFarthing et al, 2022 ). Unknowns that remain unaddressed include whether patients with specific genetic forms of the disease or who carry risk loci such as LRRK2 and GBA1 mutations will make good candidates for cell therapy strategies.…”

Precision medicine for Parkinson’s disease: The subtyping challenge

“…Moreover, degeneration in other non-dopaminergic systems and emergence of non-motor or treatment-resistant motor symptoms such as cognitive impairment, dementia, autonomic dysfunction, and gait impairment, makes management of PD, especially in later stages, more challenging. Despite tests of interventions to potentially slow disease progression ( McFarthing et al, 2022 ), there are no approved therapies that modify the underlying pathophysiological causes of PD’s neurodegenerative process.…”