New Alzheimer's Disease Drug Produces Mixed Results in Clinical Studies

In an effort to help patients diagnosed with mild-to-moderate Alzheimer’s disease (AD), drug manufacturer Roche announced the results of a pair of clinical studies on its investigational medication, crenezumab, at the recent Alzheimer’s Association International Conference (AAIC) in Copenhagen, Denmark.

According to a statement from the company, the goal of the medication is to “delay cognitive and functional decline” in patients. However, Roche said a randomized, double-blind, parallel-group, placebo-controlled study on the drug “did not meet its co-primary endpoints in people with mild-to-moderate AD.” Nevertheless, the ABBY study did show “initial evidence of a crenezumab treatment effect in people with mild AD,” as the medication had some success in slowing the decline of cognitive abilities when measured on a 12-item cognitive subscale, according to the company.

In the study, 431 patients with a Mini-Mental State Examination (MMSE) score between 18 and 26 received a low dose of 300 mg subcutaneous crenezumab every other week or a high dose of 15 mg/kg intravenous (IV) crenezumab every 4 weeks, or placebo for 68 weeks.

Those who received the higher dose of crenezumab showed a 16.8% reduction in cognitive decline and a 3.1% reduction in global functional, according to the company. However, “there was no significant change in cognition in patients who received low-dose subcutaneous crenezumab,” and there was “no effect” on global functioning, Roche noted.

Still, “in an exploratory analysis of people with milder disease treated with intravenous crenezumab, there was a positive trend toward increasing reduction in cognitive decline in progressively milder subsets relative to placebo,” according to the statement.

A smaller study known as BLAZE showed a similar slowing of cognitive decline in those with a more mild form of the disease. In that study, 91 patients with a baseline MMSE score between 18 and 26 and a positive amyloid positron emission tomography (PET) scan received either 300 mg of subcutaneous crenezumab every other week or 15 mg/kg IV crenezumab every 4 weeks for 68 weeks. Since the patients enrolled in the BLAZE study “tested positive for an amyloid imaging biomarker,” the goal of treatment was “a change in brain amyloid load,” the company said.

The results of the study showed patients who received the higher dose saw a 10.3% reduction in cognitive decline and a 7.4% reduction in global functional decline. But, just like the ABBY study, there was no “significant cognitive change” among patients who received the lower dose.

Richard Scheller, PhD, Executive Vice President and Head of Research and Early Development at Genentech, said that although the drug did not meet some of the study endpoints, “data from these phase 2 studies provide valuable information about crenezumab’s potential clinical activity in people with AD, where there is a great need for treatment options.”

According to the company, there was no imbalance in overall adverse events, but there was a disparity in cases of serious and non-serious pneumonia diagnoses. Of the total number of participants, 3.2% developed pneumonia while taking the medication, compared to just 0.6% of those who received placebo.

There were a total of 5 deaths among those taking crenezumab, but the study investigators determined the deaths were not related to the drug. There was only one reported case of asymptomatic amyloid-related imaging abnormalities.