Roche's Aβ Monoclonal Antibody Crenezumab Fails Again in Alzheimer’s Phase II Trial

On June 16, Roche and Banner Alzheimer's Institute jointly announced that crenezumab did not meet the primary endpoint in the Phase II clinical trial of the Alzheimer's Prevention Initiative (API) project.

This is a randomized, double-blind, placebo-controlled Phase II clinical trial aimed at evaluating the potential of crenezumab to slow or prevent Alzheimer's disease in a Colombian subgroup population with normal cognitive function but carrying autosomal dominant mutations (indicating a risk for familial Alzheimer’s disease). The study enrolled 252 participants, who were randomly assigned to receive either crenezumab or a placebo over a period of 5-8 years. Among them, 94% of the participants completed the study.

The results showed that the trial did not demonstrate a clinically significant benefit in either of the two co-primary endpoints: change in cognitive function or episodic memory performance. These endpoints were assessed through the integrated cognitive score and the Free and Cued Selective Reminding Test (FCSRT), respectively.

Small numerical differences favoring crenezumab were observed in multiple secondary and exploratory endpoints, but they were not statistically significant. No new safety issues with crenezumab were identified during the study. Further analyses of the data are currently underway. Initial data will be presented on August 2, 2022, at the Alzheimer's Association International Conference (AAIC).

Crenezumab is a specific monoclonal antibody drug targeting β-amyloid protein, suitable for patients with early (prodromal or mild) Alzheimer's disease. In 2006, Genentech and AC Immune reached a co-development agreement for crenezumab. In 2009, Roche acquired Genentech for $47 billion, obtaining the Aβ monoclonal antibody AD drug crenezumab.

In 2014, the Phase II study of crenezumab failed as it could not significantly delay cognitive and functional decline in patients with mild to moderate Alzheimer's disease compared to placebo, failing to meet the primary endpoint. In January 2019, Roche announced the termination of two Phase III CREAD1 and CREAD2 clinical studies of crenezumab for the treatment of early AD because interim analysis results from the independent data monitoring committee indicated that crenezumab might not achieve the primary endpoint of improving patients' Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores. (See: Roche halts two Phase III trials of crenezumab; AC Immune’s stock price plunges 66%)

However, Roche is still conducting clinical trials of the Aβ monoclonal antibody gantenerumab for Alzheimer's disease, with the latest Phase III study results expected to be announced in the fourth quarter of 2022.