Another Anti-Beta-Amyloid Drug Bites It

Eli Lilly announced today that it is pulling the plug on semagacestat, a gamma secretase inhibitor in phase 3 development for Alzheimer disease. Preliminary results from 2 large, ongoing, multinational phase 3 trials* showed that AD patients taking semagacestat actually performed worse on measures on cognition and activities of daily living than placebo-treated patients. Semagacestat treatment was also associated with a relatively increased risk of skin cancer (although the company's press release did not indicate what kind of skin cancer).

Lilly says it is still moving forward with its phase 3 clinical trials of another anti-beta-amyloid compound in AD: solanezumab, a monoclonal antibody. The drug works differently than semagacestat, an inhibitor of the enzyme (gamma secretase) that produces beta amyloid. The company also assures everyone that it will publish the results of its semagacestat trials.

By my estimation, Lilly is/was the frontrunner in clinical AD trials. Late-phase study of another anti-amyloid mAb, Pfizer/JNJ's bapineuzumab, has been complicated by underwhelming efficacy results and vasogenic brain edema.

* IDENTITY and IDENTITY-2.

Photograph of atrophied brain from person with AD: National Institute on Alcohol Abuse and Alcoholism.