Eli Lilly is canning further development of its pivotal-stage Alzheimer disease candidate, semagacestat. Data from two Phase III trials showed that the gamma secretase inhibitor not only fails in terms of slowing disease progression but actually had a detrimental effect on cognition and the ability of patients to perform daily activities.
The firm stressed that Phase III trials of its other late-stage Alzheimer disease candidate, solanezumab, will continue. While both these drugs act on amyloid-beta proteins, Lilly points out that they have different mechanisms of actions.
The Identity and Identity-2 trials evaluated semagacestat in some 2,600 patients with mild-to-moderate Alzheimer disease. Data from a planned interim analysis showed that semagacestat didn’t slow disase progression. All patients demonstrated a decline in terms of cognition and ability to perform everyday tasks as their disease progressed, whether treated using the Lilly drug or placebo. Moreover, both these measures of clinical outcome worsened to a greater degree in the semagacestat cohorts. The Lilly candidate was also associated with an increased risk of skin cancer, the firm admits.
Describing the news as “disappointing,” Jan M. Lundberg, Ph.D., Lilly’s evp, science and technology and president of Lilly Research Laboratories, reports that while the findings represented a setback, “Lilly’s commitment to beating Alzheimer’s will not waver.”
The firm is now contacting its trial centers so patients can be informed to stop taking semagacestat immediately. It will also continue to evaluate data from the studies and to collect safety data, including cognitive scores for at least six months. In addition to solanezumab, Lilly’s Alzheimer disease pipeline includes candidates in Phase I and Phase II development.