AC Immune SA has announced positive interim results from its Phase 2 VacSYn trial of ACI-7104.056, an active immunotherapy targeting alpha-synuclein (a-syn) for early-stage Parkinson's disease (PD). The trial demonstrated that ACI-7104.056 induced a significant antibody response in treated patients after six weeks. The company anticipates making a decision regarding Part 2 of the study, potentially involving up to 150 patients, based on additional interim data expected in the first half of 2025.
Immunogenicity and Safety Profile
The VacSYn trial is a two-part, multicenter, placebo-controlled, double-blind, randomized study designed to assess the safety, tolerability, immunogenicity, and pharmacodynamic effects of ACI-7104.056 in patients with early PD. Interim data revealed that the immunotherapy increased anti-a-syn antibody levels by an average of 16-fold compared to the placebo group after three immunizations. The treatment also demonstrated a favorable safety profile.
According to Andrea Pfeifer, CEO of AC Immune SA, the initial Phase 2 data are encouraging, reinforcing the potential of ACI-7104.056 as a best-in-class active immunotherapy for Parkinson's disease. The observed level of immunogenicity after only three months of treatment, coupled with the continued positive safety profile, supports the further development of this therapeutic approach.
Trial Design and Patient Population
The trial includes a screening period of up to eight weeks, followed by a 74-week double-blind treatment period and a 26-week post-treatment follow-up period. Part 1 of the study included over 30 patients randomized to either ACI-7104.056 or placebo in a 3:1 ratio. The primary endpoint is safety and tolerability, with secondary endpoints including immunogenicity and pharmacodynamic effects. The most common adverse events reported were transient injection site reactions (49%) and headaches (18%), with no other clinically relevant safety issues observed.
Mechanism of Action
ACI-7104.056 is an optimized formulation of AC Immune's anti-a-syn active immunotherapy, designed to generate a target-specific antibody response against pathological a-syn. This mechanism aims to inhibit the spread of a-syn and subsequent neurodegeneration in early PD. The interim results indicated that the antibody response was effectively induced against the target antigen at week 6 after two immunizations and was described as "strongly boostable" by the company.
Pfeifer emphasized the importance of active immunotherapies in targeting hallmark pathological proteins of neurodegenerative diseases, such as a-synuclein in Parkinson's disease, before irreversible damage occurs. ACI-7104.056 has previously been assessed in a Phase 1 study, demonstrating safety and tolerability for up to 3.5 years of treatment. The Phase 1 study, published in The Lancet Neurology, showed that ACI-7104.056 induced a strong response, with a 50% reduction in oligomeric a-syn in cerebrospinal fluid.
