A new drug delivery pump system aims to improve the treatment of advanced Parkinson’s disease
Parkinson’s disease (PD) is a chronic neurological disease with no cure, and many existing treatments have significant drawbacks or offer only short-term effects. This new system uses two known drugs (Foslevodopa/Foscarbidopa) in a revolutionary delivery mechanism, showing marked improvements in treating patients with advanced PD.
The basics: PD treatment and drug delivery modernised
This study looks at the individualised, continuous (24-hour/day) subcutaneous infusion of foslevodopa/foscarbidopa for patients with advanced PD. Foslevodopa and foscarbidopa are soluble prodrug formulations of levodopa and carbidopa, respectively. Prodrugs are drug precursors that convert into the active form, enhancing their absorption and effectiveness. In this case, foslevodopa converts to levodopa, the most effective medication for treating the motor symptoms seen in advanced PD. Levodopa and carbidopa are both orally administered and are considered the gold-standard pharmacological treatment for motor symptoms in PD.
Continuous Subcutaneous Infusion (CSCI) is a drug delivery method in which medication is continuously administered under the skin using a portable pump. This technique offers several advantages over traditional drug delivery methods as it helps to maintain stable blood concentrations of the medication. CSCI is particularly beneficial for managing chronic conditions such as PD, which require consistent therapeutic levels.
What they found
The study consisted of a 12-month, single arm (in which everyone enrolled in the trial received the therapy), open-label (investigators and trial participants are aware of the treatment group they are participating in), phase 3 study.
The continuous 24-hour/day infusion of foslevodopa/foscarbidopa significantly improved motor fluctuations. Specifically, “On” time without troublesome dyskinesia increased by an average of 3.8 hours, and “Off” time decreased by 3.5 hours from baseline. The treatment was generally well-tolerated, and the most common adverse events were infusion site reactions, mostly mild or moderate. The researchers also observed improvements in several quality-of-life measures, including the PD Sleep Scale-2, the 39-item PD questionnaire, and the EuroQol 5-dimension questionnaire.
Not so fast
This open-label, single-arm study has a few drawbacks. The lack of a control group makes it difficult to determine whether observed effects are due to the treatment or factors such as the placebo effect or disease progression (slightly alleviated by the previous study being a randomised, double-blind trial). A potential bias inherent to the open-label nature, the short term, and the lack of randomisation can also negatively impact the conclusion we can draw from this work.
While most adverse events were mild or moderate, notable adverse events in over one-quarter of patients indicate a need for careful monitoring. This is tied to the number of patients (107/244) who discontinued the study, which could impact the results.
Why does it matter?
The study uses a nonsurgical treatment for advanced PD. Traditional oral medication for PD is often less effective in the advanced stages due to fluctuating plasma levels of the drug levodopa; the CSCI method in this study maintains stable drug levels, reducing motor fluctuations and improving symptoms. These results not only have implications for advanced PD but also for the intravenous drug delivery system used, which can also work for several other disorders, such as chronic pain management and opioid infusion, which could make a real-world improvement in an individual’s overall quality of life.
1. Continuous 24-hour/day subcutaneous infusion of foslevodopa/foscarbidopa by a drug delivery pump significantly improved motor fluctuations in patients with advanced PD.
2. Treatment was generally well-tolerated, with the most common adverse events being infusion site reactions.
3. Improvements in non-motor symptoms, such as sleep quality and overall quality of life, were also observed.
Guest author: Conor McQuaid PhD
This article was written as part of a series of ‘journal club’ summaries for Scientific Writers Ltd and is based on the following publication.
First Author:Aldred J, et al.
Journal: Neurology and Therapy
Date online: 26 August 2023
Other references:
https://bmcpalliatcare.biomedcentral.com/articles/10.1186/s12904-020-00681-3
