A busy year ahead for Parkinson’s disease

As several big pharma companies drop Parkinson’s projects, attention turns to gene therapies and repurposing diabetes drugs.

Parkinson’s disease research has ended in numerous dead ends despite substantial efforts over many years. Recently, Biogen and Sanofi scrapped their Parkinson’s candidates, cipanemab and venglustat respectively, owing to lack of efficacy, and a disease-modifying therapy has yet to materialise.

But the push to find drugs that help beyond reducing symptoms continues, and Evaluate Vantage has delved into the pipeline of projects in active late-stage clinical trials. This year is shaping up to be crucial for the field, with 10 studies expected to yield data or to complete in 2021.

One target that crops up multiple times is GLP-1; this approach, traditionally employed in type 2 diabetes, is also being tested in Alzheimer’s. Among other avenues of research, it is hoped that gene therapy could offer a one-time cure for Parkinson’s.


Research has suggested that GLP-1 agonists have neuroprotective benefits, and several trials of marketed diabetes drugs, as well as new GLP-1-targeting projects, are under way in Parkinson’s. Some of these studies are investigator sponsored, including the most advanced, a UCL-run phase III trial of Astrazeneca’s Bydureon called Exenatide-PD3.

This study aims to build on an earlier trial by the same research group that showed that, at 60 weeks, off-medication scores on the rating scale MDS-UPDRS had improved by 1.0 points in the exenatide group and worsened by 2.1 points in the placebo cohort. Results are some way off, with the clinicaltrials.gov primary completion date of Exenatide-PD3 in 2023.

In the meantime, data are expected from several phase II studies of GLP-1 agonists, including a trial of Novo Nordisk's Victoza, being run by Cedars-Sinai Medical in collaboration with the Danish company and The Cure Parkinson's Trust. That study is set to complete in September.

September will also see the completion of a mid-stage trial of Peptron's sustained-release exenatide formulation PT320.

Neuraly is also evaluating a new formulation of exenatide, this time a pegylated version; peglylation is said to increase permeability through the blood-brain barrier. That project is further behind Peptron’s, with its phase II trial set to complete next year.

Gene therapies

While gene therapies could offer a longer-term solution, this approach has suffered its fair share of setbacks recently, and Parkinson’s disease has been no exception: Voyager’s VY-AADC was put on clinical hold in December after abnormalities were seen on patients' MRI scans. Voyager’s partner Neurocrine subsequently dropped the project.

Other groups hoping for a better outcome include Sio Gene Therapies with AXO-Lenti-PD, a lentiviral vector project designed to restore levels of dopamine via the delivery of three genes needed for dopamine synthesis. The hope is that this will stabilise disease and reduce L-dopa medication; still, the asset is an updated version of Oxford Biomedica's Prosavin, which generated weak efficacy and was ultimately abandoned. 

In the first two cohorts of the phase II Sunrise-PD study, AXO-Lenti-PD led to promising improvements in the UPDRS Part III “off” score, albeit in a very small number of patients.

The project has been hit by manufacturing delays, however, and the processes to provide clinical trial material for larger studies have yet to be finalised. 

Big pharma groups are also getting involved in gene therapy, most recently Lilly, which bought Prevail last December for $880m up front, gaining the Parkinson’s candidate PR001. The AAV-based project aims to transfer the GBA1 gene that encodes the enzyme beta-glucocerebrosidase, which is required for the disposal and recycling of glycolipids. It is estimated that as many as 7-10% percent of Parkinson’s patients worldwide carry at least one GBA1 mutation.

The phase I/II Propel trial of PR001 is ongoing, and before Prevail’s acquisition the company said it would provide biomarker and safety analysis on a subset of patients by mid-2021.

Other early-stage deals, such as Abbvie's move to corner the preclinical researcher Mitokinin yesterday, show that big companies are also interested in exploring other novel technologies.

With a respectable roll call of late-stage trials gearing up to read out, the coming years will hopefully yield bigger steps forward in this disease. 

Selected active disease-modifying projects in Parkinson's disease (Ph2 and 3)
Project Description Company Trial, primary completion
GLP-1 receptor agonist Astrazeneca Ph3 Exenatide-PD3, Jun 2023, sponsored by UCL
Anti-α-synuclein MAb Roche/Prothena Ph2b due to start Q2 2021 (ph2 Pasadena failed) 
AAV-GAD AAV GAD gene therapy Meiragtx Completed ph1 and ph2, IND expected H1 to start new trial
Amyloid precursor protein, alpha-synuclein & tau inhibitor Annovis Bio/Horizon Therapeutics Ph2, initial data due early 2021, dose-response data due late summer
C-C chemokine receptor type 3 antagonist Alkahest Ph2 Teal, Mar 2021
CNM-Au8 Gold nanoparticles Clene Nanomedicine Ph2 Repair-PD, Apr 2021
SAGE-718 NMDA modulator Sage Therapeutics Ph2 open-label Paradigm, Jun 2021, topline early 2021
NYX-458 NMDA modulator Aptinyx Ph2, Jun 2021
SR-Exenatide (PT320) GLP-1 receptor agonist Peptron Ph2, Sep 2021
Liraglutide (Victoza/Saxenda) GLP-1 receptor agonist Novo Nordisk Ph2, Sep 2021, sponsored by Cedars-Sinai Medical Center
GLP-1 receptor agonist Sanofi Ph2 Lixipark, Sept 2021, sponsored by University Hospital, Toulouse
Muscarinic & sigma-1 receptor agonist Anavex Life Sciences Improvements in cognitive tests in ph2OLE ongoing, Oct 2021
AXO-Lenti-PD Dopamine gene therapy Sio Gene Therapies/Oxford Biomedica Promising results from first two cohorts in ph2 Sunrise-PD; ph2 Explore-PD to start 2021
NLY01 (pegylated exenatide) GLP-1 receptor agonist D&D Pharmatech/Neuraly Ph2, Jul 2022
CDNF Parkinson’s Project Cerebral dopaminergic neurotrophic factor Herantis Pharma Ph1/2 showed serious adverse events related to the surgery and drug administration process; ph1/2 long-term safety study, Sep 2022
GLP-1 receptor agonist Astrazeneca Ph2, Oct 2022, sponsored by Center for Neurology Stockholm and Karonlinska Institutet
(K0706, SCC-138, vodobatinib)
BCR-ABL tyrosine kinase inhibitor Sun Pharma Advanced Research Ph2 Proseek, Mar 2023
UCB0599 Alpha-synuclein aggregation inhibitor UCB Ph2, Oct 2023
PR001 AAV GBA1 gene therapy Lilly/Prevail Therapeutics Ph2 Propel, biomarker data mid 2021, completes Jun 2027
Sources: EvaluatePharma, clinicaltrials.gov & company releases.

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