AC Immune (ACIU) Study result summary

Study design and safety

• VacSYn is a randomized, double-blind, placebo-controlled Phase 2 trial in early Parkinson’s disease; Part 1 enrolled 34 participants, with 25 assigned to ACI-7104.056 and 9 to placebo.

• Part 1 assessed safety, tolerability, and immunogenicity over 18 months of treatment, followed by 6 months of safety follow-up; exploratory endpoints included biomarkers and clinical activity correlations.

• Primary safety and tolerability endpoints were met, with no significant safety concerns; common adverse events included injection-site reactions, headache, and fatigue.

• Six serious adverse events, including two deaths, were considered unrelated or unlikely related to study drug; the Data Safety Monitoring Board recommended continuing without modification.

Immunogenicity and target engagement

• 100% of active-arm participants developed antibodies against the target after three immunizations; titers increased with further doses and were at least twofold higher than with previous formulations.

• Antibodies were detected in CSF in all treated participants, with levels rising by week 24 and increasing further by week 76.

• Induced antibodies preferentially bind aggregated alpha-synuclein; testing also reported binding to Lewy bodies in post-mortem Parkinson’s disease brains.

Exploratory biomarkers and clinical signals

• CSF total alpha-synuclein and NfL trends appeared stable in the active arm, while placebo showed declines in total alpha-synuclein and an NfL increase; findings were exploratory in a small sample.

• Higher antibody titers were associated with smaller changes in MDS-UPDRS Part III scores; the correlation strengthened from weak at week 48 to moderate-to-good at week 76 and was also observed for Part II scores.

• DaTSCAN showed no signal decrease through week 48 and a decline at a later time point; investigators cautioned that the study was not powered to assess imaging differences.

• No clear correlation was observed between antibody titers and total alpha-synuclein levels; exploratory aggregated alpha-synuclein analyses suggested an effect but require caution given the low participant numbers.