Trial of Potential Alzheimer’s Vaccine Advances to Medium Dose Group

Testing of a second and higher dose of ACI-35.030, a potential Alzheimer’s vaccine, is now beginning in a Phase 1b/2a clinical trial, AC Immune announced.

Positive interim safety, tolerability, and specificity results from an initial dosing group of patients allowed the trial to advance to its medium dosing regimen, the company reported in a press release.

ACI-35.030, being developed in collaboration with Janssen Pharmaceuticals, mimics the structure of the toxic version of the tau protein — phosphorylated tau — that underlies key features of Alzheimer’s pathology, such as disrupted communication between nerve cells.

By triggering an immune reaction to phosphorylated tau, the antibodies generated by ACI-35.030 have the potential to limit the occurrence and spread of tau pathology throughout the brain.

“The fact that ACI-35.030 shows encouraging safety and immunogenicity at the lowest dose in this elderly patient population is highly meaningful and we look forward to quickly enrolling this next dosing group,” Anrea Pfeifer, AC Immune’s CEO, said in the release.

“Tau-targeted approaches may have a much broader therapeutic window to potentially disrupt, slow or prevent disease progression at both early and advanced disease stages. Pathological pTau occurs early in the disease process, years before accumulation of Tau deposits,” Pfeifer said, adding “our pTau-targeting approach holds significant promise for the treatment of [Alzheimer’s] at different disease stages.”

The placebo-controlled trial (NCT04445831) is assessing the safety, tolerability, and immunogenicity (its ability to provoke an immune response) of different doses of ACI-35.030 over 48 weeks of treatment in people with early Alzheimer’s. Secondary endpoints include clinical and cognitive changes, as well as additional immunogenicity and safety parameters.

The trial is actively recruiting at locations in Finland, the Netherlands, and the U.K. More information on locations and contacts can be found here. About 24 adults in total, ages 50 to 75, are planned to take part in this study.

ACI-35.030 had shown a positive safety profile and high specificity for toxic forms of tau in preclinical studies. The vaccine candidate triggered a strong and long-lived antibody immune response against phosphorylated tau in these studies.

AC Immune is also advancing semorinemab, a monoclonal antibody against phosphorylated tau, in collaboration with Genentech and Roche.

Semorinemab is currently in a Phase 2 clinical trial (NCT03828747), that is recruiting an estimated 260 adults with moderate Alzheimer’s at sites in the U.S., France, Poland, and Spain.