Trial of experimental Parkinson’s vaccine shows positive initial results
ACI-7104 was generally safe, triggered an immune response against its target
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- The experimental vaccine ACI-7104 targets early Parkinson’s disease by aiming to reduce toxic alpha-synuclein clumps in the brain.
- Initial Phase 2 trial results showed the vaccine was safe and successfully triggered a strong immune response.
- The study will advance into Part 2 to gather further clinical proof-of-concept data and monitor symptom progression.
ACI-7104, AC Immune’s experimental vaccine for early Parkinson’s disease, was generally safe and triggered an immune response against aggregated alpha-synuclein, according to results from the first part of a Phase 2 trial.
The findings from the VacSYn study (NCT06015841) included 34 participants, 25 who received ACI-7104 and nine who received a placebo. The company said the first part of the study met all primary goals, including those related to safety, tolerability, and immunogenicity, or the ability to generate an antibody response to the vaccine’s target.
“The results from the complete data set at week-100 in Part 1 are encouraging, with all primary endpoints met, strong immunogenicity demonstrated, and a 100% response rate,” Martin ZĂĽgel, MD, AC Immune’s interim CEO, said in a company press release. Â
The VacSYn trial continues in Part 1 and is advancing toward the initiation of Part 2. The final design of the second part of the study will be submitted to the U.S. Food and Drug Administration for review, with meetings expected early in 2027. The second part aims to generate clinical proof-of-concept data and to monitor the progression of Parkinson’s symptoms, as well as digital, imaging, and fluid biomarkers.
“We will now refine our approach to the next development steps in the program and discuss our plans with regulators before embarking on an expanded Phase 2 trial designed to provide evidence of clinical activity as the basis for entry into Phase 3,” Zügel added.
ACI-7104 an optimized version of another experimental vaccine
Parkinson’s is marked by the loss of nerve cells that produce dopamine, a chemical messenger involved in controlling movement. Dopamine depletion contributes to the disease’s motor symptoms, such as tremor, slowness of movement, and stiffness.
A hallmark of Parkinson’s is the accumulation of misfolded alpha-synuclein into toxic clumps inside nerve cells. Single alpha-synuclein molecules can assemble into smaller structures called oligomers, which can then develop into larger fibrils. Alpha-synuclein oligomers are thought to be the main drivers of nerve damage and inflammation in Parkinson’s.
ACI-7104 is an optimized version of Affitope PD01A, an experimental vaccine originally developed by Affiris and acquired by AC Immune in 2021. The company is developing ACI-7104 as an active immunotherapy, meaning it is designed to train a person’s own immune system to produce antibodies against a disease-related target.
The vaccine contains a lab-made small protein that mimics part of alpha-synuclein. Its modified design is intended to stimulate the production of antibodies that preferentially recognize aggregated forms of alpha-synuclein, particularly toxic oligomers, while sparing normal single molecules. By binding these abnormal forms, the antibodies may help promote their clearance and potentially limit further aggregation.
The approach builds on earlier studies of Affitope PD01A. In the Phase 1 program, the vaccine was generally well tolerated and generated antibodies against alpha-synuclein that were detectable in blood and cerebrospinal fluid (CSF, the fluid that surrounds the brain and spinal cord). At the higher dose, treatment reduced CSF alpha-synuclein oligomers by 51%, indicating that the antibodies were engaging the intended target.
Safety data demonstrated favorable benefit-risk profile
In preclinical studies using post-mortem brain tissue from people with Parkinson’s, ACI-7104 selectively reacted with aggregated alpha-synuclein but not with single molecules.
The ongoing VacSYn Phase 2 trial is evaluating ACI-7104 in adults with early-stage Parkinson’s. The first part enrolled 34 participants (mean age 62.1 years, 65% men), who were randomly assigned to receive ACI-7104 or placebo, administered as intramuscular injections at predefined intervals (immunizations) over 74 weeks (about 1.5 years).
The safety data demonstrated an overall favorable benefit-risk profile, and most side effects were transient and generally mild. They mainly included injection site reactions (55.9%), followed by fatigue, headache, and common cold.
We are pleased to have observed strong and boostable immune responses, with significant antibody penetration into the CSF and signals for target engagement.
At week 100 (about two years), all participants who received ACI-7104 had developed antibodies against the vaccine’s alpha-synuclein target after three immunizations. The company also reported that the antibodies were detected in the CSF, with levels increasing after additional doses.
Preliminary analysis indicated that the antibodies engaged aggregated alpha-synuclein in the CSF, while levels of neurofilament light chain, a biomarker of nerve damage, remained stable. Exploratory analyses also suggested associations between antibody levels and measures of disease activity.
“We are pleased to have observed strong and boostable immune responses, with significant antibody penetration into the CSF and signals for target engagement,” said Günther Staffler, PhD, AC Immune’s executive vice president of development. “Together with the favorable safety profile … and exploratory correlations between antibody titers and disease activity measures, we are confident that these results provide a strong foundation for the continued development of ACI-7104 into Part 2.”
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