Immunotherapeutic vaccine developer Vaxxinity has announced positive results from Part B of its Phase 1 clinical trial for UB-312, an investigational vaccine for Parkinson’s disease. The trial demonstrated that UB-312 was well-tolerated and induced anti-alpha-synuclein (aSyn) antibody responses in participants with early PD, meeting the primary objectives of the trial.
The end-of-study results from Part B showed that 92% of patients who completed dosing with UB-312 developed anti-alpha-synuclein antibodies. The vaccine was generally safe and well-tolerated, with an adverse event profile similar to the placebo group. Antibodies were also detectable in the cerebrospinal fluid (CSF), indicating their ability to cross the blood-brain barrier.
“These positive Phase 1 results demonstrate several important features necessary for an immunotherapy against Parkinson’s disease and other synucleinopathies to be successful, and represent a further proof-of-principle for Vaxxinity’s platform in chronic disease,” said Mei Mei Hu, CEO of Vaxxinity.
“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. Together these results support the further development of UB-312 in a Phase 2 clinical trial.”
UB-312 is an investigational synthetic peptide vaccine designed to target toxic forms of aggregated alpha-synuclein, a protein implicated in the development and progression of PD. The Phase 1 trial consisted of two parts: Part A involved testing escalating doses of UB-312 versus placebo in healthy volunteers, while Part B tested two doses of UB-312 versus placebo in subjects with early PD. Both parts were conducted at the Centre for Human Drug Research (CHDR) in the Netherlands.
“A vaccine against alpha-synuclein is a revolutionary concept that can be of immense impact in treating neurodegenerative diseases such as Parkinson’s disease and synucleinopathies,” sais Geert Jan Groeneveld, MD, PhD, Professor of Clinical Neuropharmacology at Leiden University Medical Center and principal investigator of the Phase 1 trial.
While the Phase 1 trial primarily focused on safety, tolerability, and immunogenicity, exploratory measures of Parkinson’s disease progression were also assessed. However, the trial was not designed or powered to detect differences between UB-312 and placebo on these measures. The Michael J Fox Foundation is funding a 2-year collaborative project between Vaxxinity, the Mayo Clinic and the University of Texas Houston to evaluate target engagement and characterize the anti-alpha-synuclein antibodies after treatment with UB-312.
