A one-year, phase 2 clinical trial of Type 2 diabetes drug lixisenatide has reported positive early results, which indicate that the treatment may slow the progression of motor (or movement) symptoms. Preliminary results of the LixiPark study were presented at the International Parkinson and Movement Disorder Society annual congress in Copenhagen on 28 August, with full results analysis expected to be published in early 2024.
The LixiPark study involved 156 people with Parkinson’s. The trial met its primary endpoint – the efficacy measures that the trial set out to achieve – as ‘topline’ results showed that the progression of motor symptoms in those receiving the lixisenatide treatment slowed, while motor symptoms in participants receiving the placebo, or dummy drug, continued to progress.
Led by Professors Olivier Rascol and Wassilios Meissner at the University Hospitals of Toulouse and Bordeaux, the trial involved 21 different research centres of the NS-Park network across France. The study, sponsored by the Toulouse University Hospital, was co-funded by Cure Parkinson’s, Van Andel Institute, US and the French Ministry of Health, with drug and placebo support from pharmaceutical company Sanofi.
Lixisenatide was prioritised for clinical testing through our 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, GLP-1R agonists have demonstrated beneficial actions in the brain.
These preliminary results are important because they represent the second clinical trial of GLP-1R agonists in people with Parkinson’s to have demonstrated a positive result. The results of a previous small clinical ‘pilot’ trial of another GLP-1R agonist called exenatide suggested that those people with moderate Parkinson’s treated with exenatide for 12 months showed improvement in their motor symptoms. The recent LixiPark study was much larger than the exenatide pilot study and involved 21 research centres across France; the LixiPark study results replicate the earlier exenatide results. 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.
Cure Parkinson’s is proud to have supported this study. We congratulate the investigators who conducted it, and we thank the participants and their families. The initial results are very encouraging and provide further evidence that this class of diabetes drugs is doing something interesting in 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 which is likely to be a phase 3 clinical trial of lixisenatide 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 Parkinson’s. The study was what is termed ‘double-blind’ which means neither the participants nor the principal investigators knew which of 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 was funded by Cure Parkinson’s (with support from Van Andel Institute) and the French Government, with Sanofi providing the drug and placebo.
What are the different stages of clinical trials?
There are primarily three phases of testing a drug or compound in people. They are called ‘clinical’ testing and follow different phases. 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 long-time safety and effectiveness of the potential treatment.
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.
What will happen next?
These results are the topline preliminary results that are being presented in a poster session by the LixiPark principal investigators at the Movement Disorders Society meeting in Copenhagen at the end of August. We need to wait to see the full report of the study results which will hopefully be published early 2024. We are working with the investigators to plan the next phase of development.
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 must 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). Other 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 the results will hopefully be available in the second half of 2024.
