AC Immune SA has reported positive interim results from its Phase 2 VacSYn trial of the active immunotherapy ACI-7104.056 in early Parkinson’s disease (PD), providing the first signals that targeting alpha-synuclein (a-syn) pathology could slow disease progression.

The data, from an adaptive, placebo-controlled, biomarker-based study, showed stabilization of key disease-related markers, including cerebrospinal fluid (CSF) a-syn levels and neurofilament light (NfL), while clinical assessments suggested a trend toward stabilization of motor symptoms. Additional biomarkers, such as plasma glial fibrillary acidic protein (GFAP) and dopamine transporter (DaT) SPECT imaging, also showed trends consistent with potential disease modification.

Dr Andrea Pfeifer, CEO of AC Immune, said: “The interim Phase 2 data shows the potential of our ACI-7104.056 active immunotherapy to slow the progression of Parkinson’s disease and hold the promise of a tremendous step forward for millions of patients. The consistent signs of efficacy, combined with the continuing strong safety record, underline ACI-7104.056’s potential to transform PD treatment and are a strong basis for accelerating development. We will discuss ACI-7104.056 with the regulators to establish a clinical development plan towards registration.”

Werner Poewe, MD, emeritus Professor of Neurology at Innsbruck Medical University, added: “The remarkable consistency of the trends observed across multiple disease-related biomarkers and on clinical assessments in the treatment arm are very promising. Importantly, clinical and biomarker outcomes provide signals that the immunological response elicited by ACI-7104 may be associated with beneficial effects on PD progression. Overall, these findings are highly encouraging and fully support further development of the program. For the first time, we are seeing signals that targeting the underlying pathology of Parkinson’s with active immunotherapy could slow disease progression.”

VacSYn includes 34 patients randomized 3:1 to ACI-7104.056 or placebo. All participants in this interim analysis have received at least 12 months of treatment, with 20 participants treated for up to 18 months.

All predefined immunogenicity targets were met. Serum antibody titers were over 500-fold higher than placebo at week 76, and CSF antibody levels also increased, showing that antibodies cross the blood-brain barrier. Changes in CSF and serum antibody concentrations were strongly correlated.

Biomarkers of PD pathology in the central nervous system indicated potential disease modification. Total CSF a-syn levels stabilized in the treatment arm while declining in the placebo group (post-hoc analysis p=0.018). NfL levels remained stable in the active arm but increased in placebo. Plasma GFAP and DaT SPECT imaging also suggested stabilized pathology.

Clinical assessments reflected these findings. At week 74, minimal progression in MDS-UPDRS Part III scores was observed in the active arm, compared with expected progression in the placebo group. Stratification by L-DOPA ON/OFF state further emphasised differences between groups.

ACI-7104.056 was generally safe and well tolerated, with no clinically relevant or serious drug-related adverse events. Most common adverse events were transient injection site reactions (56%), headaches (15%) and fatigue (12%).

AC Immune plans to seek regulatory feedback on a clinical development plan to potentially accelerate registration. Final Part 1 data from VacSYn are expected in mid-2026.