Lilly to halt development of potential Alzheimer's disease drug semagacestat

Eli Lilly and Company (NYSE: LLY) will halt development of semagacestat, a gamma secretase inhibitor being studied as a potential treatment for Alzheimer's disease, because preliminary results from two ongoing long-term Phase III studies showed it did not slow disease progression and was associated with worsening of clinical measures of cognition and the ability to perform activities of daily living.

The company's decision does not affect the ongoing clinical trials of solanezumab, Lilly's other compound in Phase III trials as a potential Alzheimer's treatment. While both drugs focus on amyloid-beta proteins, which are believed to play a critical role in Alzheimer's disease, they have different mechanisms of action. Lilly also has two other compounds in earlier stages of clinical development; those studies are not affected by today's announcement.

In two pivotal Phase III trials, semagacestat was compared with placebo in more than 2,600 patients with mild-to-moderate Alzheimer's disease. Lilly has now reviewed data from a pre-planned interim analysis of semagacestat studies. This interim analysis showed that, as expected, cognition and the ability to complete activities of daily living of placebo-treated patients worsened.  However, by these same measures, patients treated with semagacestat worsened to a statistically significantly greater degree than those treated with placebo. In addition, data showed semagacestat is associated with an increased risk of skin cancer compared with those who received placebo.

"This is disappointing news for the millions of Alzheimer's patients and their families worldwide who anxiously await a successful treatment for this devastating illness," said Jan M. Lundberg, Ph.D., Executive Vice President, Science and Technology, and President, Lilly Research Laboratories. "This is a setback, but Lilly's commitment to beating Alzheimer's will not waver."

Lilly is instructing clinical trial investigators for all semagacestat studies to contact study participants as soon as possible and tell them to immediately stop taking the study drug they have received. Study participants or caregivers should call their study physician to schedule their next appointment. Lilly has appropriately informed regulatory agencies and is providing instructions to investigators outlining the process for finalizing the studies.

Lilly's clinical team will continue to gather and evaluate data from these studies, and will publish the results for the benefit of future Alzheimer's research. Although dosing with semagacestat is being stopped, Lilly plans to continue collecting safety data, including cognitive scores, for at least six months through regularly scheduled follow-up visits with study physicians and modifications of the existing Phase III protocols.  These additional follow-up visits will help to answer a number of important questions, including whether the differences between patients who received semagacestat and those who received placebo will continue after semagacestat has been discontinued. Other smaller short-term studies will be stopped and participants will receive appropriate follow-up.

The decision to halt development of semagacestat is expected to result in a third-quarter charge to earnings of approximately $.03 to $.04 per share. The company confirmed its previous 2010 earnings per share guidance range of $4.44 to $4.59 on a reported basis, or $4.50 to $4.65 on a non-GAAP basis.

"We are clearly disappointed by the results we are announcing today. However, Lilly's innovation strategy, based on advancing a pipeline of nearly 70 molecules currently in clinical development, does not rest on the success or failure of any single compound," said John C. Lechleiter Ph.D., Lilly's chairman and chief executive officer. "Pharmaceutical research always carries risk, as these results show. But it offers as well the potential for tremendous reward for millions of patients who await new medicines. Despite this and other recent setbacks, Eli Lilly and Company remains financially strong and is even more determined to prevail in our quest to provide new treatments for Alzheimer's and other serious diseases."

SOURCE Eli Lilly and Company