In June 2023 Vaxxinity announced positive results from Part B of the Phase I clinical trial of UB-312, an investigational vaccine for Parkinson’s disease. The results show that the vaccine was well tolerated and induced anti-alpha-synuclein (aSyn) antibody responses in participants with early Parkinson’s disease. The primary endpoints of the trial were met and support the advancement of UB-312 to Phase II trials.
Parkinson’s disease and aSyn
Parkinson’s disease (PD) affects over 10 million people across the globe. It is a “chronic and progressive neurodegenerative disorder”, affecting predominately dopamine-producing (dopaminergic) neurons in the substantia nigra part of the brain. There are no approved disease- modifying therapeutics and current treatments aim to provide symptomatic relief whilst causing “significant side effects”.
Alpha-synuclein (aSyn) is a protein that is highly expressed in neurons, mostly at presynaptic terminals. Mutations in the gene encoding aSyn are “known to cause or increase the risk of developing PD” and have been shown to alter the secondary structure of aSyn. This produces misfolded and aggregated forms of the protein. Immunotherapies that target aSyn have demonstrated an ability to “ameliorate aSyn pathology” and functional deficits in mouse models of PD.
UB-312 in trial
The investigational vaccine is a synthetic peptide vaccine targeting toxic forms of aggregated aSyn to address PD and other synucleinopathies. The Phase I trial was placebo controlled and double blind, comprising two parts. Part A tested escalating doses of UB-312 against placebo in 50 health volunteers between the ages of 40 and 85. Part B tested two doses of UB-312 versus placebo in 20 age-matched subjects with early PD. These were conducte at the Centre for Human Drug Research (CHDR) in the Netherlands.
Previous results from 2022 have suggested that the vaccine is highly immunogenic. All individuals in the target dose group showed detectable anti-aSyn antibodies in serum and cerebrospinal fluid (CSF).
A closer look at Part B
Part B comprised a 20-week treatment period before 24 weeks of observation. The study evaluated the safety, tolerability, and immunogenicity of the vaccine in patients with PD, and primary endpoints were met. 92% of patients who completed the dosing developed anti-aSyn antibodies. The vaccine was “generally safe and well-tolerated” and all serious adverse events (SAEs) were resolved.
A promising candidate
Vaxxinity’s CEO Mei Mei Hu, whom we interviewed at the Congress in Washington this year, commented that the results demonstrate “several important features necessary for an immunotherapy”.
“UB-312 was observed to safely break immune tolerance, inducing antibodies against toxic aggregated forms of alpha-synuclein. Importantly, these antibodies crossed the blood brain barrier, and the data also suggest potential target engagement in the periphery, where pathological alpha-synuclein is known to be concentrated.”
She considers the candidate “promising” and looks forward to further development. Dr Geert Jan Groeneveld is the CMO/CSO of CHDR and principal investigator of the Phase I trial. He commented that this is a “revolutionary concept” that could have “immense impact” in the treatment of diseases like Parkinson’s.