Objective: We tested biweekly infusions of IV immunoglobulin (IVIg) as a possible treatment for mild to moderate Alzheimer disease (AD) dementia.
Methods: In a phase 3, double-blind, placebo-controlled trial, we randomly assigned 390 participants with mild to moderate AD to receive placebo (low-dose albumin) or IVIg (Gammagard Liquid; Baxalta, Bannockburn, IL) administered IV at doses of 0.2 or 0.4 g/kg every 2 weeks for 18 months. The primary cognitive outcome was change from baseline to 18 months on the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale; the primary functional outcome was 18-month change on the Alzheimer's Disease Cooperative Study–Activities of Daily Living Inventory. Safety and tolerability data, as well as serial MRIs and plasma samples, were collected throughout the study from all enrolled participants.
Results: No beneficial effects were observed in the dual primary outcome measures for the 2 IVIg doses tested. Significant decreases in plasma Aβ42 (but not Aβ40) levels were observed in IVIg-treated participants. Analysis of safety data showed no difference between IVIg and placebo in terms of the rate of occurrence of amyloid-related imaging abnormalities (brain edema or microhemorrhage). IVIg-treated participants had more systemic reactions (chills, rashes) but fewer respiratory infections than participants receiving placebo.
Conclusions: Participants with mild to moderate AD showed good tolerability of treatment with low-dose human IVIg for 18 months but did not show beneficial effects on cognition or function relative to participants who received placebo.
Merck & Co Inc said on Tuesday it will halt a late-stage trial of an Alzheimer's drug after it was determined that it had no chance of working, marking the latest in a long line of crushing disappointments in efforts to find an effective treatment for the mind-wasting disease.
The company was testing its drug, verubecestat, in patients with mild to moderate Alzheimer's disease. But an independent data monitoring committee determined that there was "virtually no chance of finding a positive clinical effect" and recommended the trial be stopped for futility.
The news sent Merck shares down nearly 2 percent in after hours trading.
Verubecestat belongs to a class of experimental Alzheimer's drugs called BACE1 inhibitors that target an enzyme involved in the formation of the toxic amyloid protein that turns into plaques in the brains of Alzheimer’s patients.
Several companies are pinning hopes on Alzheimer's treatments using the BASE inhibitor mechanism, including Eli Lilly and Co, Biogen and Novartis in collaboration with Amgen Inc.
Lilly previously endured multiple failures with its solanezumab, which also targets beta amyloid, but in a different way. In the most recent setback, Lilly said that drug failed to slow declines in mental capacity of patients with even mild symptoms.
Researchers are increasingly focusing on attacking the disease earlier as it appears likely that once symptoms have taken hold current approaches fail to work.
Merck said another study of its drug in patients with prodromal, or very early, Alzheimer's disease would continue with results expected by February 2019.
Patients with prodromal Alzheimer's disease have objective memory problems but relatively normal functioning in activities of daily living.
Blinded clinical trials use independent monitors to watch for any unexpected safety problems that may crop up. They can also recommend stopping a study early if it becomes clear that a drug is going to fail or if the data looks so compelling that it believes the treatment should be offered to those getting a placebo or other standard treatments.
Merck shares fell to $64.48 in extended trading from a close at $65.66.