Recently, at the 2024 International Conference on Alzheimer’s and Parkinson’s Disease (AD/PD), held March 5-9 in Lisbon, Portugal, AC Immune SA presented an industry symposium on the latest clinical advances in the diagnosis and treatment of alpha-synuclein pathologies. In the symposium, the company provided an update of its phase 2 VacSYn trial (NCT06015841) assessing ACI-7104.056, an anti-α-synuclein (αSyn) active immunotherapy designed to induce αSyn specific antibodies for Parkinson disease (PD).1
“The goal is to use the patient's own immune system to produce antibodies directly, specifically to the target pathological species. We believe particularly as we compare this form of therapy, active immunotherapy with monoclonal antibodies, that they are perfectly poised to tackle [the unmet need in patients],” Nuno Mendonca, MD, chief medical officer at AC Immune SA, presented in a webcast of the industry symposium.2 “The study is currently being enrolled in Spain, UK and Germany. We are close to finalizing part 1. As of the data cut off, which was February, we have 26 patients enrolled 14 in Spain, 2 in Germany, and 10 in the UK.”
Top Clinical Takeaways
- AC Immune SA's VacSYn trial, focusing on active immunotherapy, demonstrates a promising approach in addressing α-synuclein pathologies in PD.
- Safety and tolerability remain paramount concerns, but early data from the trial show mild to moderate adverse events with no severe treatment-related issues reported.
- The ongoing study highlights the potential of utilizing patients' immune responses to target specific pathological species, potentially addressing the unmet needs in PD treatment.
VacSYn is a 2-part, prospective, multicenter, placebo-controlled, double-blind, randomized study that aims to investigate the safety, tolerability, immunogenicity, and pharmacodynamic effects of ACI-7104.056 vaccination in patients with early stages of PD. The trial will comprise of a screening period of up to 8 weeks, a 74-week double-blind treatment period, and a 26-week post-treatment follow-up period. It will include up to 3 cohorts comprised of 16 participants each, with 12 under the study vaccine and 4 under placebo. In the event that one of the initial cohorts expands to reach up to 150 participants, the randomization ratio will be adjusted to achieve an active treatment/placebo ratio of 2:1.
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In early January, AC Immune SA announced the completion of enrollment for cohort 1 in the VacSYn trial (n = 16) as well as the initiation of cohort 2 enrollment and randomization. In the announcement, the company noted that there were no safety concerns reported to date andno reports of moderate or severe adverse events (AEs). AC Immune SA also announced that updates on the safety and immunogenicity from the trial will be reported in the second half of 2024.3
“[For] safety of the study so far, as the cutoff date of February, we have seen no deaths and no additional serious treatment emergent [AEs] or other [AEs] leading to discontinuation of the study. The most common [AEs] are site injection site reactions described as redness and itching. So far, all [AEs] are mild or moderate in severity, but this is still a very small sample for the study,” Mendonca said in the webcast.2
In the presentation, Mendonca also spoke about the start of work with ACI-7104.056, known as PD01A, in a phase 1 study that assessed immunizations of the therapy in patients with PD.4 “The vaccine showed to be safe and well tolerated up to the 3 and a half years it was dosage. It also induced a strong response in this population. Compared to baseline, evidence of target engagement measured as a 50% reduction in oligomeric α-synuclein in [cerebrospinal fluid]. In addition, there was other correlations between alpha synuclein oligomers and some clinical measures” Mendonca said in the webcast.2
Published in The Lancet Neurology, patients were randomly assigned 1:1 to receive 4 subcutaneous immunizations with 15 μg or 75 μg PD01A and followed up initially for 52 weeks, and then followed by a further 39 weeks' follow-up. Patients were then randomly assigned 1:1 again to receive the first booster immunization at 15 μg or 75 μg and followed up for 24 weeks. In addition, all patients received a second booster immunization of 75 μg and were followed up for an additional 52 weeks. All patients (n = 24) experienced at least 1 AEs, but most were considered unrelated to study treatment. Systemic treatment-related [AEs] reported were fatigue (n = 4), headache (n = 3), myalgia (n = 3), muscle rigidity (n = 2), and tremor (n=2).
“The vaccine study is a 2-part [trial] being conducted in early patients with PD and multiple biomarker inference to allow for faster acceleration into wider clinical stages. So far, we have shown a good safety and tolerability profile and are close to finishing randomization of part 1,” Mendonca concluded in the webcast.2
REFERENCES
1. AC Immune Announces Upcoming Presentations At AD/PD™ 2024. News Release. AC Immune. Published February 22, 2024. Accessed March 26, 2024. https://ir.acimmune.com/news-releases/news-release-details/ac-immune-announces-upcoming-presentations-adpdtm-2024
2. State-Of-The-Art Of Treatment And Diagnosis Of Alpha-Synuclein Pathologies. Webcast. AC Immune.Presented at: AD/PD; March 5-9, 2024. Industry Symposium. Accessed March 27, 2024. https://ir.acimmune.com/events/event-details/adpdtm-2024-symposium
3. AC Immune Progress Update On Phase 2 Active Immunotherapy Clinical Pipeline For Alzheimer's And Parkinson's Diseases. News Release. AC Immune. Published January 3, 2024. Accessed March 27, 2024. https://ir.acimmune.com/news-releases/news-release-details/ac-immune-progress-update-phase-2-active-immunotherapy-clinical
4. Volc D, Poewe W, Kutzelnigg A, et al. Safety and immunogenicity of the α-synuclein active immunotherapeutic PD01A in patients with Parkinson's disease: a randomised, single-blinded, phase 1 trial. Lancet Neurol. 2020;19(7):591-600. doi:10.1016/S1474-4422(20)30136-8
