Eli Lilly and AstraZeneca have announced that they will discontinue phase 3 trials of their BACE inhibitor lanabecestat for the treatment of Alzheimer's disease, according to a BioPharma Dive report. The AMARANTH study in early Alzheimer's disease, its extension study, as well as the DAYBREAK-ALZ trial in mild Alzheimer's disease dementia will all be stopped. The companies will work with clinical trial sites to discontinue the trials. The decision was made after an independent data monitoring committee determined the trials would not meet their primary endpoints. No safety concerns were raised. The companies said they will continue their alliance, which was initially inked in 2014.
The drumbeat of Alzheimer's disease drug failures marches on. This announcement is hardly the first, or the largest, disappointment in the space. The last decade has been littered with costly, late-stage trial setbacks.
This is, in part, due to a lack of understanding around the science of the brain. Researchers have long hypothesized the buildup of amyloid plaques seen in the brains of people with Alzheimer's could be the cause of the disease. By that thinking, destroying those plaques might help reverse progression of the debilitating neurological condition. Yet, failure after failure has called that hypothesis into question.
In recent years, companies still chasing the amyloid hypothesis have tried moving earlier in the disease's development in order to prevent the formation of the plaques in the first place. While a number of medications have shown success in doing that, they still have not shown improvement in cognitive function.
As of the start of 2018, there were 112 compounds in the pipeline for the treatment of Alzheimer's—26 of which were in phase 3 testing across 35 trials, according to a report written by researchers from the Cleveland Clinic. The report noted nearly two-thirds of these drugs were meant to be disease modifying.
Another reason for the high failure rate in the space has been the lack of diagnostics and biomarkers, according to the article. Currently, it's difficult to diagnose patients until they have progressed to advanced forms of the disease. Diagnosing early patients that might not yet have symptoms is the goal for many pharmaceutical companies, but continues to be elusive. Some companies are using diagnostics to test for the presence of amyloid, but again, this is reliant on the amyloid hypothesis being correct.
Lilly and AstraZeneca said they would continue their alliance. But they aren't the only big companies to face recent disappointment in the space. In May, Johnson & Johnson announced that it would discontinue the development of its BACE inhibitor atabecestat after liver safety issues were flagged, determining that the risk–benefit profile was unfavorable.
Source: BioPharma Dive; June 12, 2018.