An investigational vaccine, ACI-7104, designed to treat individuals in the early stages of Parkinson’s disease, is exhibiting a favorable safety profile and tolerability in an ongoing Phase 2 clinical trial. Interim findings also indicate that the vaccine effectively induces the production of anti-alpha-synuclein antibodies at high levels.
Developed by AC Immune, ACI-7104 (also known as ACI-7104.056) functions as an immunotherapy. It stimulates the immune system to generate antibodies that target clumps of alpha-synuclein, which are implicated in the damage and death of dopamine-producing neurons, ultimately leading to Parkinson’s disease.
Targeting Alpha-Synuclein with Immunotherapy
Parkinson’s disease is characterized by the progressive loss of dopamine-producing neurons, crucial for motor control. This neuronal damage is believed to be caused by the misfolding of the alpha-synuclein protein, which forms toxic aggregates that spread throughout the brain, causing inflammation and further damage. ACI-7104 aims to counteract this process by prompting an immune response against alpha-synuclein oligomers, thereby promoting the clearance of these toxic clumps and slowing or halting the progression of Parkinson’s.
The vaccine consists of a lab-made protein fragment that mimics a portion of the alpha-synuclein protein, enabling it to be recognized by the immune system. By triggering an immune response, ACI-7104 is designed to clear toxic alpha-synuclein clumps, preventing further aggregation and slowing disease progression.
Phase 2 VacSYn Trial Details
The Phase 2 VacSYn trial (NCT06015841) is evaluating the vaccine’s safety, tolerability, pharmacodynamics (effects on the body), and immunogenicity (ability to trigger immune responses) in adults across sites in Germany, Spain, and the U.K. In the trial's first part, over 30 patients were randomly assigned to receive intramuscular injections of ACI-7104 or a placebo at predefined intervals over 74 weeks.
Interim Results and Next Steps
Interim data from the Phase 2 trial indicate that ACI-7104 is well-tolerated, with no clinically relevant safety concerns identified, except for transient injection site reactions (49%) and headaches (18%). After three administrations, ACI-7104 induced an average 16-fold increase in anti-alpha-synuclein antibodies compared to placebo, with all treated patients developing antibodies against alpha-synuclein.
AC Immune anticipates further trial updates in the first half of 2025, including a decision on whether to proceed to the trial's second part. This second part would involve enrolling nearly 120 additional patients, aged 40 to 75, who would be randomized to receive either ACI-7104 or a placebo. Evaluations will include assessments of safety, motor and non-motor disease symptom progression, and fluid, imaging, and digital biomarkers.
The larger second part of the trial aims to gather proof-of-concept evidence supporting the vaccine’s potential benefits in early Parkinson’s disease, which could pave the way for a pivotal clinical trial. According to AC Immune CEO Andrea Pfeifer, the initial VacSYn data supports the approach of using active immunotherapies to target pathological proteins of neurodegenerative diseases before irreversible damage occurs.
