Alzheimer's treatment fails to meet primary endpoints in phase 3 trial

Gantenerumab, a treatment for mild cognitive impairment due to Alzheimer’s disease, did not meet the primary endpoint of slowing cognitive decline in a phase 3 clinical trial, Genentech announced in a released statement.

“So many of our families have been directly affected by Alzheimer’s, so this news is very disappointing to deliver,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Genentech, said in the release. “While the [study] results are not what we hoped, we are proud to have delivered a high quality, clear and comprehensive Alzheimer’s dataset to the field, and we look forward to sharing our learnings with the community as we continue to search for new treatments for this complex disease.”

According to the release, the trial was divided into two arms, with gantenerumab slowing clinical decline by –0.31 in the first arm and –0.19 in the second. However, neither was statistically significant. In addition, the level of beta-amyloid removal was lower than expected with treatment.

Genentech also reported amyloid-related imaging abnormalities, with a pooled rate of 25% in both study arms. A vast majority of abnormalities were asymptomatic, and few led to treatment discontinuation.

Howard Fillit, MD, co-founder and chief science officer at the Alzheimer’s Drug Discovery Foundation (ADDF), released a statement following Genentech’s announcement.

“While this is discouraging news for the many patients and families living with Alzheimer’s, anti-amyloid therapies are just a starting point in new therapies for Alzheimer’s patients,” Fillit said. “If you’ve seen one anti-amyloid therapy, then you’ve seen one anti-amyloid therapy. The results we’ve seen from drugs in this class point to the urgent need to bring a range of amyloid and non-amyloid therapies to market to slow the course of Alzheimer’s disease.”

In September, Biogen and Eisai announced results from an anti-amyloid therapy trial of lecanemab. Compared with those who received placebo, patients who received lecanemab showed a reduction in cognitive decline by 27% after 18 months.

According to a recent ADDF analysis of Alzheimer’s clinical trials, more than three in four drugs in clinical trials focus on non-amyloid targets.

“Successes and disappointments are an expected part of the scientific process, but we are unmistakably in a modern era of Alzheimer’s research, on the cusp of a new generation of therapies that will take a more holistic approach to treating the disease by targeting all of its underlying causes,” Fillit said. “Years of relentless work by Alzheimer’s researchers has built the foundation to conduct more rigorous trials, allowing us to measure the effectiveness of new drugs more efficiently.”