An independent data monitoring committee has recommended that Eli Lilly and AstraZeneca discontinue development of their Alzheimer’s drug lanabecestat based on the prediction that the oral beta secretase cleaving enzyme (BACE) inhibitor was unlikely to meet its primary endpoint in late-stage trials. The companies have decided to follow this advice and, as a result, both their AMARANTH and DAYBREAK-ALZ trials will be stopped.
This is just the latest in a long line of clinical failures in the Alzheimer’s space as the neurodegenerative disease proves difficult to treat. Eli Lilly was testing their BACE inhibitor in both early Alzheimer’s and mild Alzheimer’s dementia, with both discontinued trial programs being in the all-important Phase III.
“The complexity of Alzheimer’s disease poses one of the most difficult medical challenges of our time, and we are deeply disappointed for the millions suffering from this devastating disease,” said Dr. Daniel Skovronsky, president of Lilly Research Labs. “We are grateful for the contributions of the study participants and their families and encourage them to consider other Alzheimer’s disease clinical trials. Lilly remains dedicated to Alzheimer’s disease research as we have been for the last three decades. We won’t give up on finding a solution for Alzheimer’s patients.”
In a release about the decision, Eli Lilly emphasized that concerns regarding the safety of lanabecestat were not behind the committee’s recommendation to cease development of the drug. Lilly and AstraZeneca formed their BACE Alliance to develop lanabecestat in 2014 and the companies say the partnership remains in place.
“We are saddened by this outcome as our researchers are working tirelessly to find a solution for the many people who are impacted by this devastating disease,” said Dr. Menelas Pangalos, Executive Vice President, IMED Biotech Unit, AstraZeneca. “We are committed to ensuring our findings can be used to inform further research in the Alzheimer’s community, given the importance of finding a treatment for this disease.”
Patients with early Alzheimer’s disease were enrolled in the placebo-controlled AMARANTH trial which sought to have those in the treatment arm achieve a change from baseline on the 13-item Alzheimer’s Disease Assessment Scale – Cognitive Subscale (ADAS-Cog13). Those who completed this study were offered the chance to get the active treatment in the AMARANTH extension trial, a program which will now also be discontinued.
The DAYBREAK-ALZ trial had the same endpoint as AMARANTH but enrolled patients with mild Alzheimer’s disease dementia.
The challenging field of Alzheimer’s clinical development has proven too much for some pharmaceutical companies. In January, Pfizer announced it would be cutting its neuroscience division in an effort to focus more on disease areas where the company has had proven success. But as drugmakers drop out of the Alzheimer’s drug development race, the potential payoff for an effective dementia treatment remains a real driver for those companies still in the game.