Anti-pTau Vaccine Induces Intended Immune Response in Ongoing Trial
ACI-35.030, an experimental anti-tau vaccine that AC Immune is developing for Alzheimer’s disease, was able to potently induce an immune response as intended and was generally well-tolerated, according to 10-week interim data from a Phase 1/2 clinical trial.
“These latest interim results add to the robust clinical dataset supporting plans for continued late-stage development,” Andrea Pfeifer, PhD, CEO of AC Immune, said in a press release.
Alzheimer’s is characterized by the formation of abnormal aggregates (clumps or tangles) of a protein called tau in the brain. A particular version of tau, called phosphorylated tau or pTau, is particularly prone to forming aggregates. These atypical clumps are thought to be toxic to brain cells, driving disease progression.
ACI-35.030 is a vaccine designed to promote an immune response against pTau, triggering immune cells to make antibodies that target the abnormal protein and ultimately break up disease-driving protein clumps. AC Immune is developing ACI-35.030 in collaboration with Janssen Pharmaceuticals.
The ongoing Phase 1b/2a trial (NCT04445831), sponsored by AC Immune, is testing three doses of ACI-35.030 (low, medium, or high) against a placebo in people with early-stage Alzheimer’s. The mid-dose group was recently expanded to include 24 participants, from the original eight.
In the trial, the vaccine is administered via injection into the muscle, with injections given at the study’s start, and again after eight weeks, 24 weeks, and 48 weeks (about a year).
New 10-week interim data showed that treatment with the highest tested dose of ACI-35.030 “led to the strong induction of antibodies selective for pTau and its aggregated form,” according to AC Immune. These results are consistent with earlier data from the two lower tested doses, which showed that median levels of anti-pTau antibodies increased at two weeks after the first injection.
The new data also highlight that antibodies generated in response to ACI-35.030 are selective for pTau, not the unmodified version of the protein: ratio of anti-pTau to anti-tau antibodies increased continually over the course of 10 weeks. Levels of antibodies against disease-driving tau were boosted after both the first and second injections.
“The observed antibody response also shows a preference for pathological pTau, which is present in AD [Alzheimer’s] years before Tau accumulation can be detected via brain imaging,” Pfeifer said.
Safety data from the ongoing trial have generally been positive. According to AC Immune, there have been “no clinically relevant safety concerns” observed so far.
“With these results we believe ACI-35.030 holds significant promise as a first-in-class therapeutic that could shift the AD treatment paradigm towards earlier treatment and prevention, especially when used alongside cutting-edge pTau diagnostics as part of a precision medicine approach,” Pfeifer said. “We look forward to the continued development of ACI-35.030.”