In a significant setback for Parkinson's disease research, AstraZeneca's diabetes medication Bydureon (exenatide) has failed to demonstrate efficacy in slowing disease progression in a Phase III clinical trial. The study, conducted by University College London (UCL), delivers disappointing results despite earlier promising preclinical data.
The Exenatide-PD3 trial enrolled 192 participants to evaluate the potential of the glucagon-like peptide 1 receptor agonist (GLP-1RA) in modifying Parkinson's disease progression. Participants received either weekly doses of 2mg Bydureon or placebo over the study period.
Clinical Trial Results
The trial's primary endpoint, measured using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) while patients were off their regular Parkinson's medication, showed discouraging results at the 96-week mark. The Bydureon group experienced a mean increase of 5.7 points in MDS-UPDRS III scores, indicating worse disease progression compared to the placebo group's 4.5-point increase.
Safety data revealed comparable profiles between the treatment arms, with 9% of Bydureon-treated patients experiencing at least one serious adverse event, compared to 11% in the placebo group.
Expert Commentary
Trial lead Tom Foltynie addressed the results at the Cure Parkinson's Autumn research update meeting with stark clarity: "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."
Scientific Context
The disappointing outcome presents a puzzling contrast to extensive preclinical research. Foltynie noted the drug's impressive performance in laboratory studies, where exenatide showed significant benefits in animal models exposed to toxins or alpha-synuclein-preformed fibrils. Additionally, diabetic patients taking Bydureon have shown reduced risk of developing Parkinson's disease.
Broader Implications
This trial follows the Phase II LixiPark trial, which tested Sanofi's GLP-1RA Lyxumia (lixisenatide) in Parkinson's patients and showed more promising results over a 12-month period. The contrasting outcomes highlight the complexity of translating preclinical success to clinical benefit in neurodegenerative diseases.
The research community continues to explore GLP-1RAs across various therapeutic areas. Beyond metabolic disorders, these agents are being investigated in gastrointestinal, cardiovascular, and central nervous system conditions, reflecting their potential versatility despite this setback in Parkinson's disease.
