The full results of the one-year, phase 2 clinical trial of Type 2 diabetes drug lixisenatide have now been published. This Cure Parkinson’s co-funded trial has reported positive results, indicating that the treatment may slow the progression of motor symptoms.
Researchers have reported that the LixiPark study has met its primary endpoint – the efficacy measures that the trial set out to achieve – as results showed that the progression of motor (or movement) symptoms in those receiving the lixisenatide treatment slowed, while motor symptoms in participants receiving the placebo, or dummy drug, continued to progress. Preliminary results of the LixiPark study were initially presented at the 2023 International Parkinson and Movement Disorder Society annual congress in Copenhagen, with the full results now published in The New England Journal of Medicine.
Led by Professors Olivier Rascol and Wassilios Meissner at the University Hospitals of Toulouse and Bordeaux, the trial involved 156 people within 3 years of Parkinson’s diagnosis (early-stage) across 21 different research centres of the NS-Park network in France. The study, sponsored by the Toulouse University Hospital, was co-funded by Cure Parkinson’s with Van Andel Institute (VAI; in Michigan, US), and the French Ministry of Health, with drug and placebo support from pharmaceutical company Sanofi.
Lixisenatide was prioritised for clinical testing through Cure Parkinson’s and Van Andel Institute’s International Linked Clinical Trials (iLCT) programme.
Lixisenatide belongs to a group of Type 2 diabetes medicines called glucagon-like peptide 1 receptor agonists (or GLP-1R agonists) that function by mimicking the action of a naturally occurring gut hormone that is produced after eating food. GLP-1R agonists are clinically approved for the treatment of diabetes, and, importantly, have demonstrated beneficial actions in the brain as well, making them an area of interest for Parkinson’s research.
These results are important because they represent the second clinical trial of GLP-1R agonists in people with Parkinson’s to demonstrate a positive result at phase 2. The first GLP-1R agonist to show potential for slowing motor symptoms in Parkinson’s is exenatide, which was investigated in both a small pilot study in 2008 and a phase 2 clinical trial in 2017. The recent LixiPark study was much larger than both studies but replicates the earlier exenatide results, strengthening support for some of this class of drugs. There is now a large, multicentre phase 3 clinical trial of exenatide for Parkinson’s being run across the UK, and the top-line results are due to be reported in the second half of 2024.
This is a very encouraging result for us here at Cure Parkinson’s. Along with our funding partners at Van Andel Institute, we have been championing the repurposing of GLP-1 receptor agonists for Parkinson’s since 2010. We congratulate the investigators who conducted this study, and we are truly grateful to the participants and their families for helping to advance the research into disease modifying therapies for Parkinson’s.
Dr Simon Stott, Director of Research, Cure Parkinson’s
Next steps
While these results show promising potential, it is important to note that there are currently no GLP-1R agonists, including lixisenatide, that are approved for use in Parkinson’s and further testing is required before this drug can be reviewed by regulators for use in Parkinson’s. Cure Parkinson’s is now working closely with the principal investigators of the LixiPark study to plan the next phase in the development of this interesting drug for Parkinson’s.
Q & A’s
What is lixisenatide?
Lixisenatide is a once-daily injectable GLP-1R agonist that is used in the treatment of Type 2 diabetes (brand name ‘Lyxumia’ in the EU and ‘Adlyxin’ in the USA).
What is a GLP-1R agonist?
Glucagon-like peptide 1 receptor agonists (or GLP-1R agonists) are a class of drugs used in the treatment of Type 2 diabetes. They act by mimicking the action of a naturally-produced gut hormone called GLP-1 in the body. GLP-1 is produced by cells lining the intestines when food and drink is consumed, stimulating insulin to be released by the pancreas. Insulin helps cells absorb glucose from our food (sugar) to be used as energy.
Read more about Type 2 diabetes and the connection with Parkinson’s
What is the lixisenatide ‘LixiPark’ Phase 2 clinical trial?
The lixisenatide in Parkinson’s (LixiPark) study was a 12-month phase 2 trial of GLP-1R agonist lixisenatide or a placebo drug in 156 people with early-stage Parkinson’s (diagnosed within three years, on stable dopaminergic medication, and aged between 40 to 75 years). The study was ‘double-blind’, meaning neither the participants nor the principal investigators knew whether the actual trial drug or placebo were being administered to participants.
The LixiPark study was led by Prof Olivier Rascol (University of Toulouse) and Prof Wassilios Meissner (University of Bordeaux).
The study, sponsored by the Toulouse University Hospital, was co-funded by UK charity Cure Parkinson’s, with Van Andel Institute (VAI; in Michigan, US), and the French Ministry of Health, with drug and placebo support from pharmaceutical company Sanofi.
What are the different stages of clinical trials?
There are primarily three phases of clinical testing a drug or compound in people. Phase 1 is a small study testing the safety of a potential treatment in a group of people over a short period of time. Phase 2 is a larger study assessing the safety of a potential treatment over a larger period of time in a much larger group of people who are affected by the disease. Phase 2 studies often include measures of efficacy to get an idea of whether a treatment is doing what it is supposed to do. The LixiPark trial was a phase 2 clinical trial. Phase 3 is the last stage of clinical testing and involves a very large cohort of people affected by the disease being tested for a long period of time to determine the effectiveness of the potential treatment alongside its long-term safety.
What were the results of the LixiPark Phase 2 clinical trial?
Lixisenatide treatment appeared to slow the progression of movement symptoms associated with Parkinson’s over the 12-month long study. The group who were taking the placebo drug showed continued worsening of their movement symptoms assessment scores over the course of the study, whereas participants taking lixisenatide remained near baseline.
What will happen next?
Cure Parkinson’s are working with the investigators to plan the next phase of development of GLP-1R agonists for Parkinson’s. We are also awaiting the results of the phase 2 Stockholm study and the phase 3 UK trial of exenatide, another GLP-1R agonist, in Parkinson’s. These results are expected later this year and they will help to inform next steps for this class of drugs.
I have Parkinson’s, can I take lixisenatide?
Lixisenatide is still considered to be experimental for use in Parkinson’s and more research is required. There are currently no GLP-1R agonists, including lixisenatide, that are approved for use in Parkinson’s. GLP-1R agonists are also currently considered an experimental class of drugs for Parkinson’s.
We advise that any adjustments to your current treatment regimes should be discussed with your clinician or neurologist.
Do all GLP-1R agonists used to treat Type 2 diabetes have the same effect in Parkinson’s?
There is a wide range of subtle differences between the broader class of GLP-1R agonists and they have not all been tested in Parkinson’s. Some GLP-1R agonists significantly reduce body weight (which might add concerns of frailty for people with Parkinson’s). Some GLP-1R agonists do not cross the blood brain barrier very well, and therefore are not able to have an effect in the brains of people with Parkinson’s. It is important to note that more research is required to better understand these differences in the context of a potential treatment for Parkinson’s.
The Phase 3 exenatide trial is happening now – when are the results expected?
The study finishes in the first half of 2024, so we hope the results will be available in the second half of 2024.
