AC Immune (NASDAQ:ACIU) reported results from Part 1 of its VacSYn Phase II trial evaluating ACI-7104.056, an active immunotherapy designed to target aggregated alpha-synuclein in early Parkinson’s disease.
The placebo-controlled study enrolled 34 participants, with 25 receiving ACI-7104.056 and nine receiving placebo. The trial included an 18-month treatment period followed by a six-month safety follow-up. Company executives said the study met its primary safety, tolerability and immunogenicity objectives.
Vaccine Targets Aggregated Alpha-Synuclein
Parkinson’s disease is characterized by loss of dopaminergic neurons and the presence of Lewy bodies, which contain alpha-synuclein. Günther Staffler, AC Immune’s executive vice president of development, said misfolded alpha-synuclein can aggregate, spread between cells and potentially contribute to disease progression.
ACI-7104.056 was designed to stimulate antibodies that preferentially bind aggregated alpha-synuclein rather than its monomeric form. The company changed the formulation after licensing a predecessor version from AFFiRiS, using the carrier protein CRM197. Staffler said preclinical work indicated the optimized formulation retained the antibody specificity of the earlier version while producing higher antibody titers.
According to AC Immune, all treated participants developed detectable antibody responses after three vaccinations. Antibody levels increased with subsequent doses, while placebo recipients did not show a detectable response.
The company also reported that antibodies were detected in CSF in all treated participants. Staffler said this finding indicated that antibodies generated in the periphery could reach the central compartment closest to the brain, where they could potentially bind the targeted aggregated alpha-synuclein species.
Safety Profile and Exploratory Findings
The trial enrolled patients with early-stage Parkinson’s disease, with participants evenly divided between Hoehn and Yahr stages one and two. The mean participant age was 62, and the study population included 22 men and 12 women.
AC Immune said ACI-7104.056 was safe and well tolerated to date. The most frequently reported adverse events were injection-site reactions, headache and fatigue. The Data Safety Monitoring Board recommended the trial continue without modification, according to the company.
The company also presented exploratory biomarker and clinical analyses, while emphasizing that the small study was not designed or powered to establish statistically significant efficacy.
- CSF total alpha-synuclein levels appeared to stabilize in the treated group, while the placebo group showed a gradual decline over 76 weeks.
- Neurofilament light, a nonspecific marker associated with neuronal injury, also showed a stabilization trend in treated participants compared with an increase in the placebo group.
- Higher anti-alpha-synuclein antibody titers were associated with smaller changes in MDS-UPDRS Part III motor scores, the company said.
Staffler said the relationship between antibody titers and clinical scores was not observed during the first year, but became visible at week 48 and strengthened by the end of treatment at week 76. He said correlations were seen with both MDS-UPDRS Part III and Part II measures, but noted substantial variability and the limited sample size.
The company also evaluated DaTSCAN imaging. Staffler said there was no decline in signal through week 48, but a decline was observed later. He cautioned that the study was not powered to assess differences in imaging outcomes.
Next Steps Include Expanded Study and FDA Discussions
AC Immune plans to extend Part 1 with an additional cohort receiving more frequent quarterly dosing, rather than the every-six-month maintenance schedule used after the initial priming period. Staffler said the terminal duration of the active-immunization antibody response is approximately three to four months, and quarterly administration could raise trough antibody levels.
The company also plans to follow Part 1 participants for up to four years to generate additional long-term safety information, which Zügel said is important for a potential lifelong disease-modifying treatment.
For Part 2, AC Immune is planning a trial of approximately 250 patients, with a 24-month treatment period and a six-month follow-up. The proposed study would include safety, tolerability and immunogenicity assessments, as well as digital motor-function measures, functional and patient-reported outcomes, and advanced MRI sequences intended to measure iron and neuromelanin.
AC Immune said it intends to discuss the design with the Food and Drug Administration under the Fast Track designation recently granted to the ACI-7104 Parkinson’s program. Zügel said the company expects it could begin the next trial phase in the first half of the following year.
About AC Immune (NASDAQ:ACIU)
AC Immune SA (NASDAQ: ACIU) is a clinical-stage biopharmaceutical company headquartered in Lausanne, Switzerland. Founded in 2003, the company develops precision medicines and diagnostic products designed to prevent, diagnose and treat neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and other conditions associated with misfolded proteins.
AC Immune’s research is based on its SupraAntigen and Morphomer technology platforms, which are intended to identify disease-related proteins and generate therapies or diagnostic tools that target them.
