ACI-7104, an investigational vaccine to treat people in the early stages of Parkinson’s disease, is showing safety and tolerability in a Phase 2 clinical trial, while also inducing the production of anti-alpha-synuclein antibodies at high levels, according to interim trial findings.
Being developed by AC Immune, ACI-7104 — also known as ACI-7104.056 — is an immunotherapy, meaning it works to prompt the immune system to produce antibodies targeting alpha-synuclein clumps, which damage and kill dopamine-producing neurons to cause Parkinson’s.
Further trial updates are expected in the first half of 2025, the company announced, including whether the two-part Phase 2 VacSYn trial (NCT06015841) will advance into its second part, testing the vaccine in a larger patient group.
“The level of immunogenicity after only 3 months of treatment as well as the continued positive safety profile, reinforces the best-in-class characteristics of our clinically validated anti-[alpha-synuclein] active immunotherapy for the treatment of Parkinson’s disease,” Andrea Pfeifer, AC Immune’s CEO, said in a company press release.
Vaccine aims to trigger an immune response against toxic alpha-synuclein
The progressive damage and death of neurons that produce dopamine, a major chemical messenger that is essential for motor control, causes Parkinson’s. Neuronal damage is thought to be driven by the production of a misfolded alpha-synuclein protein that is prone to forming toxic clumps that spread throughout the brain and cause inflammation.
During the aggregation process, single units of alpha-synuclein begin to clump together into chain-like structures called oligomers, which can spread and form long and thread-like fibers called fibrils.
ACI-7104 consists of a lab-made small protein fragment that mimics a portion of the alpha-synuclein protein, allowing it to be recognized by the immune system.
By triggering an immune response against alpha-synuclein oligomers, ACI-7104 is expected to promote the clearance of these toxic clumps, preventing further aggregation and helping to slow or halt Parkinson’s progression.
Previous Phase 1 trials evaluated the safety and tolerability of a predecessor therapy called Affitope PD01A in adults with early-stage Parkinson’s. Treatment was reported to be generally well tolerated, and to trigger the production of antibodies targeting toxic alpha-synuclein. ACI-7104 is considered an optimized version of that earlier therapy.
The VacSYn trial opened last year, evaluating the vaccine’s safety, tolerability, pharmacodynamics (effects on the body), and its immunogenicity, or ability to trigger immune responses, in adults at sites in Germany, Spain, and the U.K.
In the Phase 2 trial’s first part, over 30 patients were randomly assigned to intramuscular injections of ACI-7104 or a placebo at predefined times for 74 weeks (about 1.5 years).
Current plus upcoming trial data may support expanded testing
No clinically relevant safety issues were identified, except for transient injection site reactions (49%) and headaches (18%). After three treatment administrations, ACI-7104 induced an average increase in anti-alpha-synuclein antibodies 16 times higher than the placebo at background levels, with all treated patients developing antibodies against alpha-synuclein, the company reported.
Based on these and upcoming part one findings, AC Immune will decide to initiate the trial’s second part, enrolling nearly another 120 patients, ages 40 to 75, and randomizing them to treatment or a placebo. In addition to safety, evaluations will include measures of progression in Parkinson’s motor and nonmotor disease symptoms, as well as fluid, imaging, and digital biomarkers.
This larger trial part intends to collect proof-of-concept evidence of the vaccine’s benefit in early Parkinson’s, supporting the start of a pivotal clinical trial.
“We are delighted with these initial VacSYn data. They further support the approach of using active immunotherapies to target the hallmark pathological proteins of neurodegenerative diseases, such as [alpha]-synuclein in Parkinson’s disease, before irreversible damage occurs,” Pfeifer said.
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