Switzerland-based AC Immune SA announced positive interim results from its ongoing Phase Ib/IIa clinical trial of ACI-35.030 for Alzheimer’s disease.
AC Immune CEO Andrea Pfeifer pictured above. Photo courtesy of AC Immune.
Switzerland-based AC Immune SA announced positive interim results from its ongoing Phase Ib/IIa clinical trial of ACI-35.030 for Alzheimer’s disease. The vaccine showed a potent antigen-specific antibody response against phosphorylated tau (pTau) in 100% of older patients with early Alzheimer’s.
AC Immune is working in collaboration with Janssen Pharmaceutical of Johnson & Johnson.
ACI-35.030 is a potent liposomal anti-pTau vaccine. It is engineered to elicit antibodies against phosphorylated pathological Tau protein, which is associated with Alzheimer’s disease. Two abnormal proteins in the brain are linked to Alzheimer’s, beta-amyloid and pTau. Generally, although not exclusively, beta-amyloid is seen earlier and pTau is seen later in the disease. ACI-35.030 is designed to decrease and help the clearance of aggregates of Tau.
“These remarkable data show that ACI-35.030 is capable of generating unprecedented antibody responses against pTau in an elderly population, with very high antigen-specific titers,” said Andrea Pfeifer, chief executive officer of AC Immune. “Importantly, it generated a much stronger antibody response compared to direct injection of exogenous antibodies. As pathological pTau is present as a precursor many years before Tau accumulation in the brain is detectable via brain imaging, such results highlight the significant promise of ACI-35.030 as an early intervention for AD, especially when combined with cutting-edge pTau diagnostics that would enable identification of people at risk of developing Tau-driven disease.”
The data demonstrated anti-tau IgG response preferentially targeted pTau in all patients, with 100% response after the first injection at both the lowest and second highest dosages. Very high anti-pTau IgG levels were observed after injection and the IgM response was also observed in all patients for both doses. The drug was safe and well tolerated with no clinically relevant safety issues. At this time, it plans to advance to the third and highest dosing levels, per study protocol.
The drug came out of the company’s proprietary SupraAntigen platform. This technology platform speeds the discovery and development of specific antibodies and vaccine candidates. Other products to come out of the platform include ACI-24, against amyloid beta, crenezumab, an anti-Abeta monoclonal antibody, and semorinemab, an anti-Tau monoclonal antibody.
In September 2020, AC Immune and Genentech reported that semorinemab failed to hit the co-primary efficacy endpoint or two secondary endpoints in the Phase II TAURIEL study in early Alzheimer’s disease. The primary endpoint was reducing decline on Clinical Dementia Rating-Sum of Boxes (CDR-SB) compared to placebo. The two secondary endpoints were Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog13) and Alzheimer’s Disease Cooperative Study Group – Activities of Daily Living Inventory (ADCS-ADL).
At the time, Pfeifer said, “Today’s news is surprising and disappointing, given what we as a field know about Tau and its strong spatiotemporal correlation with both symptoms and pathology in AD.”
The hope of the ACI-35.030 study is that by attacking pTau, it can decrease the spread and seeding of Tau pathology, a hallmark of Alzheimer’s disease. ACI-35.030 uses a new vaccine formulation intended to achieve active immunization that improves antibody responses in older patients who might have diminished immune systems. AC Immune stated, “Notably, anti-pTau vaccination generates antibody responses with pharmacokinetic characteristics and target epitopes that differ substantially from the company’s anti-Tau monoclonal antibody semorinemab, highlighting the comprehensive and complementary nature of AC Immune’s anti-Tau pipeline.”
