The development for new treatment of Alzheimer’s disease faces another blow as Lilly and company announced that they will halt the development of semagacestat, a new agent being studied as a potential treatment for Alzheimer’s disease. The decision was based on the preliminary results from two ongoing long-term Phase III studies that showed poor effectiveness. It is noted that the drug “did not slow disease progression and was associated with worsening of clinical measures of cognition and the ability to perform activities of daily living.”
Semagacestat, known as a gamma secretase inhibitor, was designed to work by blocking an enzyme in the brain that causes the formation of a substance called amyloid. It is believed that buildups of amyloid plaque in the brain cause Alzheimer’s.
After reviewing preliminary results from 2,600 patients enrolled in two Phase III clinical trials, researchers found that patients treated with semagacestat worsened to a statistically significantly greater degree than those receiving placebo. The drug was also associated with an increased risk of skin cancer. Lilly plans to continue collecting safety data from the study, including cognitive scores, for at least six months. The company says it will publish results from the studies for the benefit of future Alzheimer’s research.
“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 has put large investment on Alzheimer’s programs including semagacestat and another candidate called solanezumab. The drugs target beta amyloid–plaque that accumulates in the brain–along different pathways. Researchers have recruited more than 1,000 patients for each of a series of late-stage trials. The company notes that its decision to axe the semagacestat program doesn’t impact ongoing clinical trials of solanezumab or two other Alzheimer’s compounds in earlier stages of development.
The decision to halt semagacestat also turns much pressure on the company’s R&D pipeline to produce new revenue sources. Lilly faces patent expirations for several top-selling drugs in the coming years, which will expose them to cheaper generic competition. The anti-psychotic Zyprexa, lilly’s blockbuster will loses patent protection next year.