AC Immune’s ACI-7104 met all primary endpoints in a Phase 2 Parkinson’s disease trial, with 100% antibody response and CSF penetration.
Written By: Mayuri Vaja, PharmD
Reviewed By: Pharmacally Editorial Team
AC Immune reported that ACI-7104 met all primary safety, tolerability, and immunogenicity endpoints through week 100 in Part 1 of the VacSYn Phase 2 trial in patients with early-stage Parkinson’s disease. The immunotherapy generated antibodies in all treated patients after three immunizations, with robust antibody penetration into cerebrospinal fluid (CSF) and exploratory biomarker findings consistent with target engagement.
Strong Immunogenicity and Favorable Safety Through Week 100
Part 1 enrolled 34 patients, with 25 randomized to ACI-7104 and nine to placebo in a 3:1 allocation. The primary endpoints were safety, tolerability, and immunogenicity.
All three endpoints were met. ACI-7104 was generally safe and well tolerated through week 100, with no new safety concern highlighted in the company’s reported findings. The announcement did not provide detailed comparative adverse-event rates between the ACI-7104 and placebo groups.
All patients who received three immunizations developed antibodies against PD01, the alpha-synuclein target antigen used for immunization. The treatment also generated antibody reactivity against aggregated forms of alpha-synuclein, which are implicated in Parkinson’s disease pathology.
Robust antibody penetration into the CSF was observed in all treated patients, indicating that the induced immune response reached the central nervous system.
Exploratory Findings Provide Evidence of Target Engagement
Part 1 was not powered or structured to establish clinical efficacy or definitive biomarker effects. However, AC Immune conducted exploratory analyses of CSF biomarkers, including total alpha-synuclein and neurofilament light chain, alongside clinical measures of disease activity.
The analysis identified a signal involving total alpha-synuclein in CSF that was consistent with preliminary target engagement. Additional exploratory correlation analyses showed trends linking antibody levels with measures of disease activity.
Because these analyses involved a limited patient population and were not primary efficacy assessments, the findings require confirmation in the planned expansion of the study.
Week-100 Assessment Completed as Part 1 Extension Continues
VacSYn is an adaptive, randomized, double-blind, placebo-controlled Phase 2 trial evaluating ACI-7104 in patients with early-stage Parkinson’s disease. The study comprises two parts.
Part 1 focuses on safety, tolerability, and immunogenicity, while Part 2 will expand the clinical evaluation to generate evidence of clinical activity that could inform a subsequent Phase 3 program.
The week-100 dataset represents the reported primary assessment of Part 1, while participants continue in a two-year extension. In parallel, AC Immune is finalizing the design of Part 2 and plans to discuss the proposed expansion with the FDA in early 2027.
ACI-7104 Targets Pathological Alpha-Synuclein
ACI-7104.056 is an optimized formulation of AC Immune’s anti-alpha-synuclein active immunotherapy approach. The program is intended to generate antibodies that preferentially recognize pathological oligomeric and aggregated alpha-synuclein species.
Alpha-synuclein aggregation is a central feature of Parkinson’s disease and has been linked to neuronal dysfunction, inflammatory stress, and progressive neurodegeneration. Targeting pathological alpha-synuclein represents an approach under investigation for modifying disease biology rather than treating symptoms alone.
The week-100 findings demonstrate sustained immune responsiveness and CNS antibody exposure, while the exploratory biomarker observations provide an early basis for further assessment of target engagement.
FDA Discussions Expected in Early 2027
AC Immune plans to use the Part 1 findings to refine the development strategy for ACI-7104 before advancing into Part 2. ACI-7104 recently received FDA Fast Track designation for early-stage Parkinson’s disease, providing a regulatory framework for more frequent interactions with the agency during development. The company expects to submit the proposed Part 2 expansion to the FDA and hold regulatory discussions in early 2027.
Martin Zügel, interim CEO of AC Immune, said the week-100 dataset supports further development based on the safety profile, antibody response, and preferential binding to aggregated alpha-synuclein.
The next major milestone will be regulatory alignment on the Part 2 design and its subsequent initiation. The expanded study is expected to provide the clinical activity data needed to determine whether ACI-7104 can progress toward Phase 3.
Reference
AC Immune Reports Positive Safety & Immunogenicity at week-100 in Part 1 of VacSYn Phase 2 Trial of ACI-7104, AC Immune, 23 September 2026
A Study to Evaluate the Effects of ACI-7104.056 in Patients With Early Stages of Parkinson’s Disease (VacSYn), ClinicalTrials.gov ID NCT06015841
About the Writer
Mayuri Vaja (Linkedin) is a Pharm.D professional with a strong interest in clinical research, pharmacovigilance, and medical writing, supported by certifications in pharmacovigilance and academic projects exploring AI in healthcare and drug safety.
With a growing focus on evidence-based healthcare and scientific communication, she is developing expertise in clinical research and translating healthcare evidence into clear, meaningful content.
As a Pharmacally healthcare writer, Mayuri is committed to creating accurate, research-driven, and clinically relevant healthcare content while continuously strengthening her professional skills.