Failed Alzheimer's trials must not be forgotten
By: Olga Uspenskaya-Cadoz, MD, PhD | March 08, 2016
Lessons learned from previous trials are supporting the next generation of Alzheimer's research.
Last fall's Clinical Trials on Alzheimer ’s Disease (CTAD) event in Barcelona, featured no groundbreaking revelations or long awaited trial results. Instead, participants focused their presentations and discussions on promising trials currently underway, lessons learned from previous efforts, and how failures from the past will drive our success in the future.
Many conversations centered on Aducanumab, Biogen’s AD drug currently tested in an ongoing large-scale phase 3 program. In March, Biogen announced that data from the Phase 1B trial showed an acceptable safety profile and positive results on neuroimaging and clinical measurements in patients with prodromal Alzheimer’s disease (AD), which is a promising development. Similarly, Eli Lilly released results from its Solanezumab trials in July that suggest the treatment effect of the drug was preserved within a pre-specified amount in patients with mild Alzheimer's disease who received solanezumab earlier in the disease. While many participants were disappointed that no further trial results were released at CTAD, there are high hopes for these drugs. If the trials continue to show positive results in patients with prodromal and mild AD, it could be a tremendous breakthrough for the industry and hope for the patients
Lessons from the past
But these trial results represented only one aspect of the event. Over three days, participants heard presentations and viewed scientific posters on broad range of research currently underway in the AD space. In one of the more thought provoking sessions was led by Eric Siemers, M.D. a Distinguished Medical Fellow of the Alzheimer’s Disease Global Development Team at Eli Lilly, who talked about the overall drug development process for AD from the point of view of the industry. Dr. Siemers touched on the many negative results in AD trials beginning as far back as 2002, and how those results shouldn’t be viewed as mere failures, but rather as opportunities that helped shape today’s research.
He argued that much of the work we are accomplishing today is built on the backs of those early trials. The results helped us better understand how to approach AD research, including the need to address the presence of both tau protein and beta-amyloid in patients’ brains, and to focus more effort on identifying diagnostics tools and preventive treatments. That knowledge lead to better imaging techniques, and the recent discoveries of new biomarkers that indicate AD far earlier in the disease’s progression. These discoveries are critical to AD trials because they enable researchers to identify patients before they are symptomatic, which allows for faster and more specific recruiting for trials. These discoveries have also reduced the probability of safety concerns, and helped researchers design targeted protocols based on the patients most likely to respond to a drug.
Registries speed research
Another important outcome of these trials is the deployment of multiple AD patient registries around the world to support trial recruiting, and to give researchers a forum to gather real world data. Some registries highlighted at CTAD include Biogen’s AHEAD registry, which plans to recruit 14,000 participants to explore changes in memory and thinking among people 50 to 85 years of age; The Alzheimer’s Prevention Registry, led by Banner Alzheimer’s Institute, to link patients with researchers working on Alzheimer’s studies; and the Brain Health registry led by researchers at UC San Francisco, in which participants complete online neuropsychological tests to help scientists study brains as they age, and to identify a pool of pre-qualified clinical trial participants for future studies. All of these registries will help accelerate AD trial recruiting, which is one of the biggest challenges with this research, and help hone the inclusion/exclusion criteria for trials based on the data these registries collect.
Several presenters also discussed the potential impact of lifestyle changes in slowing AD progression, including a session lead by Laura D Baker, PhD, from the Wake Forest School of Medicine, who discussed research showing aerobic exercise could reduce phosphorylated tau protein (a biomarker of neurodegeneration) in cerebrospinal fluid in older adults with mild cognitive impairment.
While AD research has been an often frustrating journey, it is important to acknowledge how far we’ve come and to remember that it could not have been achieved without those early failures. We still have many lessons to learn before we defeat this devastating disease, but we are much further along now thanks to those lessons learned.