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07 February 2025

Daily Newsletter

07 February 2025

AstraZeneca’s diabetes drug fails to slow Parkinson’s progression in UCL trial

Researchers concluded that the GLP-1RA showed no ability to slow disease progression in people living with Parkinson’s disease.

Joshua Silverwood February 06 2025

AstraZeneca’s diabetes drug Bydureon (exenatide) has failed to slow the progression of Parkinson’s disease motor symptoms in a Phase III trial.

The University College London (UCL) in the UK led the Exenatide-PD3 trial (NCT04232969), which sought to examine how the glucagon-like peptide 1 receptor agonist (GLP-1RA) could impact a Parkinson’s disease progression. However, results published in The Lancet detail that the trial failed to meet the primary and secondary endpoints.

The trial compared two arms, one was dosed weekly with 2mg of Bydureon and the other treated with a placebo.

The primary endpoint was measured using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) whilst off Parkinson’s medication. At 96 weeks, MDS-UPDRS III scores had increased, meaning disease progression had worsened, by a mean of 5.7 points in the Bydureon group, and by 4.5 points in the placebo group.

Additionally, of the 192 patients enrolled on the trial, 9% of participants in the Bydureon group had at least one serious adverse event compared with 11% in the placebo group.

Presenting initial findings at the Cure Parkinson’s Autumn research update meeting, trial lead Tom Foltynie said: “I am trying to be absolutely definitive about this and leave nobody in any doubt that in this population of patients, the drug did not work. It is clear, it is definitive that the drug did not change the rate of progression in this population.

“So, what does this mean? This has to be in the context of a lot of work that led to us doing this work in the first place. In the laboratory, the rats and the mice, exposed to toxins or alpha-synuclein-preformed fibrils, in all of those poor rats and mice exenatide is brilliant. It works really, really well.

“If you have diabetes and are at increased risk of Parkinson’s’ and you get given Bydureon, your risk of Parkinson’s diminishes. Why can all of that be true but when we give it to patients with Parkinson’s it doesn’t seem to make any difference?”

The trial follows on from the Phase II LixiPark trial (NCT03439943) that saw Parkinson’s patients dosed with Sanofi’s GLP-1RA Lyxumia (lixisenatide), which appeared to slow disease progression when compared to placebo in a 12-month-study. Both trials were in part funded by the UK-based charity Cure Parkinson’s.

GLP-1RAs are being investigated in several indications beyond metabolic disorders. Research by the Clinical Trials Arena found that in 2024, after metabolic disorders, gastrointestinal, cardiovascular and central nervous systems were indications where GLP-1RAs had the most research ongoing.

Elsewhere in the field of Parkinson’s disease, Mitsubishi Tanabe Pharma America has announced that a Phase III trial of its candidate, ND0612, has met its primary endpoint. Meanwhile, AbbVie and Cerevel Therapeutics have reported positive top-line results from the Phase III TEMPO-3 clinical trial evaluating a once-a-day dose of tavapadon.

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