Lessons learned in Alzheimer's drug trial move research forward
An Alzheimer’s drug that showed promising results in studies conducted in animals has not had the same outcomes in clinical trials. A group of researchers led by Baylor College of Medicine have shown that the drug Solanezumab did not improve cognition or functional ability in those with mild to moderate Alzheimer’s disease, but there may be a silver lining.
The findings are published in the current edition of the New England Journal of Medicine.
“While the results did not show a significant improvement, these findings help the field to move forward with more targeted studies,” said lead author Dr. Rachelle Doody, professor of neurology at BCM and director of the Alzheimer’s Disease and Memory Disorders Center. “The results help us to pinpoint at what stage of the disease this type of drug will be most beneficial.”
One characteristic of Alzheimer’s disease is the presence of amyloid-beta plaques, abnormal clusters of protein fragments between nerve cells which start to accumulate decades before a person develops any symptoms. One hypothesis is that if you prevent or remove these plaques, symptoms might be improved. In past lab studies using mice that also accumulate amyloid, Solanezumab, a monoclonal antibody that binds soluble amyloid-beta, was shown to reduce amyloid accumulation in the brain.
In the current studies, more than 2,000 participants with mild to moderate Alzheimer’s disease received either a placebo or solanezumab for 18 months. Using the Alzheimer’s Disease Assessment Scale, a test used to measure cognitive dysfunction, and a measure of activities of daily living researchers found there was not a significant improvement for those taking the drug compared to those given placebo. Although this primary analysis was negative, additional analyses published in the online supplement support the possibility of an effect in the milder patients.
Others who contributed to the research include: Ronald G. Thomas, Rema Raman, Xiaoying Sun, and Paul S. Aisen with the University of California at San Diego; Eric Siemers, Hong Liu-Seifert and Richard Mohs with Eli Lilly and Company; Martin Farlow at Indiana University; Takeshi Iwatsubo with the University of Tokyo; Bruno Vellas with Centre Hospitalier Universitaire Toulouse; Steven Joffe with the University of Pennsylvania; Karl Kieburtz with the University of Rochester Medical Center.
Doody, who is also the Effie Marie Cain Chair in Alzheimer's Disease Research at Baylor, along with Thomas, Farlow, Iwatsubo, Vellas, Joffe, Kieburtz, Raman, Sun and Aisen are with the Alzheimer’s Disease Cooperative Study. Siemers, Liu-Seifert and Mohs are part of the Solanezumab Study Group at Eli Lilly.
The Alzheimer’s Disease Cooperative Study Data and Publications Committee was formed as a joint partnership with Eli Lilly to facilitate, encourage and coordinate complete and accurate dissemination of the results of the Expedition I and II clinical trials as well as the medical and scientific knowledge derived therefrom. The Expedition I and II trials of Solanezumab were sponsored by Eli Lilly.