Parkinson Immunotherapy ACI-7104.056 Demonstrates Positive Antibody Responses in Phase 2 Trial Update

Andrea Pfeifer

AC Immune SA announced a positive update to its phase 2 VacSYn trial (NCT06015841) with results showing that treatment with investigational ACI-7104.056, an anti-alpha-synuclein (a-syn) active immunotherapy, resulted in positive antibody responses in treated patients with Parkinson disease (PD) after 6 weeks. The company may choose to begin Part 2 of the study with up to 150 patients, based on additional interim results, including pharmacodynamic data, expected in H1 2025.¹

VacSYn is a 2-part, prospective, multicenter, placebo-controlled, double-blind, randomized study that tests safety, tolerability, immunogenicity, and pharmacodynamic effects of ACI-7104.056 vaccination in patients with early stages of PD. In the interim update, the data revealed that treatment with the immunotherapy induced an increase in anti-a-syn antibodies on average 16-fold higher than the placebo background level after 3 immunizations.

"We are encouraged by these initial Phase 2 safety and immunogenicity data on our ACI-7104.056 active immunotherapy being studied in early Parkinson disease," Andrea Pfeifer, chief executive officer at AC Immune SA, said in a statement.¹ "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-a-syn active immunotherapy for the treatment of Parkinson’s disease. We look forward to sharing further updates in H1 2025 including the decision to expand into Part 2 of the VacSYn study."

The trial comprises a screening period lasting up to 8 weeks, a 74-week double-blind treatment period, and a 26-week post-treatment follow-up period. It includes up to 3 cohorts comprised of 16 participants each, with 12 under the study vaccine and 3 under placebo. Part 1 of the study, which included analyses from over 30 patients randomized to either ACI-7104.56 or placebo in a 3:1 ratio, showed no clinically relevant safety issues other than transient injection site reactions (49%) and headaches (18%).

READ MORE: CAP-003 Demonstrates Disease-Modifying Properties in Preclinical Study of GBA-Related Parkinson Disease

ACI-7104.056 is an optimized formulation of its clinically validated anti-a-syn predecessor active immunotherapy which generated a target-specific antibody response against pathological a-syn to inhibit spreading and downstream neurodegeneration in early PD. In the interim update, results showed a positive antibody response that was effectively induced against the target antigen at week 6 after 2 immunizations. Notably, the antibody responses were “strongly boostable” according to the company.

"As a leader in active immunotherapies for neurodegenerative diseases with two FDA Fast Track designated candidates, an important recognition of their promise, we are delighted with these initial VacSYn data," Pfeifer added, "They further support the approach of using active immunotherapies to target the hallmark pathological proteins of neurodegenerative diseases, such as a-synuclein in Parkinson’s disease, before irreversible damage occurs."¹

ACI-7104.056 was previously assessed in a phase 1 study and was found to be safe and well tolerated for up to 3 and a half years of treatment. Published in The Lancet Neurology, patients were randomly assigned 1:1 to receive 4 subcutaneous immunizations with 15 μg or 75 μg of ACI-7104.056 and followed up initially for 52 weeks, and then followed by a further 39 weeks’ follow-up. All told, treatment with the agent induced a strong response, with a 50% reduction in oligomeric a-syn in cerebrospinal fluid.²

In the study, all patients (n = 24) experienced at least 1 adverse event, but most were considered unrelated to study treatment. Systemic treatment-related AEs reported were fatigue (n = 4), headache (n = 3), myalgia (n = 3), muscle rigidity (n = 2), and tremor (n = 2).

REFERENCES
1. AC Immune Reports Positive Interim Results from Phase 2 Trial of ACI-7104.056 Active Immunotherapy in Early Parkinson’s Disease. News release. AC Immune SA. November 14, 2024. Accessed November 14, 2024. https://www.globenewswire.com/news-release/2024/11/14/2981035/0/en/AC-Immune-Reports-Positive-Interim-Results-from-Phase-2-Trial-of-ACI-7104-056-Active-Immunotherapy-in-Early-Parkinson-s-Disease.html
2. State-Of-The-Art Of Treatment And Diagnosis Of Alpha-Synuclein Pathologies. Webcast. AC Immune.Presented at: AD/PD; March 5-9, 2024. Industry Symposium. Accessed November 14, 2024. https://ir.acimmune.com/events/event-details/adpdtm-2024-symposium