Crenezumab Misses Primary Target in Alzheimer’s Trial

the Psychiatry Advisor take:

Crenezumab, a biologic medication for Alzheimer’s disease, missed its primary endpoints in a Phase II trial. Like many other drugs for Alzheimer’s under development, crenzumab targets and destroys beta-amyloid plaque in the brain, thought to be a cause of the disease.

Patients with mild to moderate Alzheimer’s in the ABBY trial that received crenezumab showed a 16.8% reduction in the cognitive decline rate at 28 weeks compared with placebo (P=0.19), according to Jeffrey Cummings, MD, director of the Cleveland Clinic’s Lou Ruvo Center for Brain Health. The results did not achieve statistical significance.

However, there was some positive news in the results. Speaking at the Alzheimer’s Association International Conference in Copenhagen, Cummings said that a subset of patients with a very mild form of Alzheimer’s (baseline Mini-Mental State Examination [MMSE] score 22 to 26) did have significant improvement when receiving crenezumab at a high dose.

In a post hoc analysis, the biologic was associated with a 35.4% slower decline in MMSE score compared with placebo (P=0.036).

A second study of crenezumab, BLAZE, showed a similar, though nonsignificant trend in clinical improvement in patients with mild disease, based on secondary clinical outcomes. BLAZE enrolled 91 patients and its primary endpoint was beta-amyloid plaque burden in the brain. Primary results are pending.

Crenzeumab’s results are similar to those with another monoclonal antibody-based drug, solanezumab. The latter medication is under investigation now for those with “preclinical” Alzheimer’s — patients with little cognitive impairment, but who have a lot of amyloid plaque in the brain.