AB1601 Phase 2 Study of ABvac40, an Anti‐Aβ40 Vaccine: Safety and Immunogenicity of a Cross‐Over Extension

• Published in: Alzheimer's & dementia Vol. 19; no. S24
• Main Authors: Pascual‐Lucas, María, Lacosta, Ana María, Canudas, Jesús, Montañés, María, Allué, Jose A, Sarasa, Leticia, Molina, Elisabet, Castillo, Sergio, Sarasa, Manuel, Terencio, Jose, Boada, Mercè
• Format: Journal Article
• Language: English
• Published: 01-12-2023
• ISSN: 1552-5260; 1552-5279
• DOI: 10.1002/alz.082952

Background
Amyloid‐β (Aβ) immunotherapy is a promising strategy for treating Alzheimer’s disease (AD). Previous studies suggested that Aβ40 could have an important role in AD, especially in relation to amyloid deposition in blood vessels in AD. The AB1601 (NCT03461276) is a multicenter, randomized, double‐blind, placebo‐controlled, phase 2 study in patients with amnestic mild cognitive impairment (a‐MCI) or very mild AD (vm‐AD) which investigated the safety, tolerability and immunogenicity of repeated subcutaneous injections of ABvac40, a vaccine targeting Aβ40. The 24‐month study (Part A) showed that ABvac40 was safe, well‐tolerated and highly immunogenic. Here, an additional 18‐month cross‐over study (Part B) was conducted to evaluate safety, tolerability and immunogenicity of ABvac40 in patients randomized to placebo in Part A (Delayed start group), and to assess safety and immunogenicity of a delayed booster of ABvac40 in ABvac40‐treated patients in Part A (Booster group).
Method
A total of 124 patients with a‐MCI (N = 80) or vm‐AD (N = 44) were initially included in Part A. Seventy‐seven out of 101 patients who completed Part A transitioned to Part B. Safety assessments included the frequency of amyloid‐related imaging abnormalities (ARIA). Immune response was assessed by quantification of specific anti‐Aβ40 antibodies in plasma samples.
Result
ABvac40 continued to show a favorable safety profile. Specifically, no ARIA‐E was reported and ARIA‐H incidence was low, equally distributed in both groups, and similar to the placebo group (Part A). Delayed start group showed a strong and specific immune response, with a time course equivalent to the ABvac40 group in Part A. A delayed booster of ABvac40 elicited a large increase in anti‐Aβ40 antibody plasma levels, exceeding the concentrations observed throughout the active dosing phase of Part A.
Conclusion
The cross‐over extension of the AB1601 Phase 2 study confirmed the excellent safety and tolerability profile of ABvac40, making this vaccine a potential candidate to be combined with other disease‐modifying therapies. Results on immunogenicity supported those obtained in Part A, demonstrating that ABvac40 elicited a strong, specific, sustained and boostable immune response. This could have important implications for long‐term treatments, especially in the context of preventive approaches. Additional exploratory efficacy results of Part B are expected in Q4‐2023.