CHICAGO – An investigational monoclonal antibody may dissolve amyloid brain plaques in patients with Alzheimer's disease, although patients receiving the vaccine did not show any signs of improved cognition during a 12-week randomized, placebo-controlled trial.
Dr. Eric Siemers, who presented the data from the trial, which was sponsored by Eli Lilly & Co., at the International Conference on Alzheimer's Disease, said the lack of cognitive improvements didn't trouble him. The phase II study was primarily intended as a safety, tolerability, and dosing trial, with cognition a secondary end point; the 12-week period was probably too short to show any cognitive changes that the antibody might induce, said Dr. Siemers, medical director of Lilly' s Alzheimer's Disease Research Team.
Importantly, the vaccine (LY2062430) was safe for the Alzheimer's patients and healthy volunteers who received it. There were no infusion reactions or drug-related adverse events, including meningoencephalitis, microhemorrhage, or edema.
The study comprised 52 patients with mild-moderate Alzheimer's (mean Mini-Mental State Exam score 20), and 16 healthy volunteers. Patients were randomized to placebo or to one of four antibody infusion dosages: 100 mg every 4 weeks, 100 mg every week, 400 mg every 4 weeks, or 400 mg every week. Volunteers got just a single 100-mg dose.
All study participants underwent magnetic resonance imaging and blood and cerebrospinal fluid (CSF) sampling to determine the level of soluble amyloid β. A subgroup of 24 patients and 13 volunteers also underwent single-photon emission computed tomography (SPECT) to determine cortical amyloid plaque load. Cognitive status was assessed by the Alzheimer's Disease Assessment Scale-Cognition (ADAS-cog).
CSF and blood samples showed that the antibody affected levels of both Aβ40 (a less-neurotoxic protein) and Aβ42 (the toxic form found in Alzheimer's brain plaques) in a dose-dependent manner. Patients taking the 400-mg/week dose had a significant decrease in Aβ40 in the CSF, but a significant increase in Aβ42, which suggests that the brain plaques were dissolving, Dr. Siemers said.
A phase III trial of the antibody is set to begin in 2009, Dr. Siemers said at the meeting sponsored by the Alzheimer's Association.