AC Immune SA also continues to develop an improved formulation of the investigational agent.
Data from an interim analysis of a phase 2 trial of AC Immune SA’s ACI-24 anti-amyloid-beta (Aß) vaccine for the prevention of Alzheimer disease (AD) suggest that the investigational agent is safe and well-tolerated in people with mild AD.1
The 18-month safety and tolerability analysis yielded no safety concerns. No evidence of central nervous system (CNS) inflammation or amyloid-related imaging abnormalities (ARIA) related to ACI-24 were seen in any participants. The phase 2 study will complete with a planned 24-month analysis of the currently enrolled participants.
Andrea Pfeifer, PhD, chief executive officer, AC Immune SA, said in a statement that “...the optimized ACI-24 formulation represents a potential breakthrough in Abeta vaccination, as it elicits a strong immune response against oligomeric and truncated Abeta, the suggested key culprits in the Abeta pathway driving early Alzheimer’s disease.”
“These exciting preclinical results, combined with the encouraging clinical safety and efficacy we have demonstrated to date for our optimized pTau vaccine ACI-35.030 as well as our first anti-Abeta vaccine candidate ACI-24, highlight the strength and versatility of our SupraAntigen-V platform for delivering safe and long-lasting active immunization against key proteinopathies in neurodegenerative diseases. We are planning to file an Investigational New Drug application for the optimized ACI-24 formulation by year-end, followed by an accelerated clinical development in Down syndrome-related AD, with start of Phase 2 as early as 2022/23,” she continued.
ACI-24 is one of the company’s SupraAntigen-derived liposomal vaccine candidates designed to convey long-lasting immunization against pathological forms of Aß. Other vaccines developed by AC Immune SA with this platform include the anti-pTau vaccine ACI-35, currently in a Phase 1b/2a clinical study, the anti-Aß antibody crenezumab, currently in a Phase 2 AD prevention trial, and the anti-Tau antibody semorinemab, in 2 phase 2 clinical trials for AD.2
The company is also developing an optimized ACI-24 formulation that has demonstrated increased and sustained immunogenicity in non-human primate studies, particularly against oligomeric and pyroglutamate Aß (pyroGlu-Aß), which it generated a strong, conformation-specific antibody response against. A robust boosting effect was also observed, with a substantially greater magnitude seen against pyroGlu-Aß compared to full-length Aß. The pyroGlu-Aß target was recently validated by encouraging clinical results in a phase 2 clinical study of donanemab, a monoclonal antibody developed by Eli Lilly specific for pyroGlu-Aß.3
“There is broad potential for our optimized Aß vaccine formulation across Aß-driven diseases, including Down syndrome-related (DS-related), genetic, and sporadic AD. We plan to complete the current Phase 2 study in mild AD and, in line with our proven business strategy, seek a strategic partner for further development for AD in the general population. This allows us to focus our in-house efforts on advancing our vaccine into later-stage clinical development to address genetically defined AD in people with DS. We look forward to initiating a follow-on clinical trial in DS as soon as the threat to this vulnerable patient population from COVID-19 subsides,” Pfeifer said in a previous statement.4
“In the interim, we are in discussions with the FDA on a potentially accelerated development pathway for the optimized vaccine formulation and expect to file an investigational new drug application for the new formulation in Q4 2021. In parallel, we are encouraged by the recent data from Aß therapeutic antibodies in AD and expect our optimized vaccine formulation data showing strong responses against pathological oligomeric and pyroglutamate Aß to further support ongoing clinical development in large and NeuroOrphan indications,” she continued.