Dr. Reisa Sperling with Brigham and Women’s Hospital is one of the nation’s top experts when it comes to Alzheimer’s disease. And it is deeply personal for her as the neurodegenerative condition hit her grandfather while she was in medical school and three years ago, she lost her father to the disease. Serving as a principal investigator in a clinical trial called “A4,” she commits to stopping this disease that robs humans of memory itself.
Sponsored by Eli Lilly and the Alzheimer’s Therapeutic Research Institute, the A4 study is a clinical trial for older individuals who have evidence of amyloid plaque build-up in their brains who may be at risk for memory loss and cognitive decline due to Alzheimer’s disease. The sponsors and investigators, thanks to participants, will test an anti-amyloid investigational drug in older individuals who do not yet show symptoms of Alzheimer’s disease cognitive impairment or dementia with the aim of slowing memory and cognitive decline. The A4 study also assesses whether anti-amyloid treatment can delay the progression of Alzheimer’s disease related brain injury on imaging and other biomarkers.
As WMC 5 Action News reported, the sponsors and investigators are utilizing online tools to screen about 15,000 participants for which nearly 4,000 came in for brain scans. Half of the study participants receive the experimental study drug called Solanezumab while the other half receive a placebo. The study concludes in 2022.
Solanezumab Prospects Not Good but Sponsor doesn’t Give Up
Solanezumab, a monoclonal antibody that binds to amyloid beta, is being evaluated as a neuroprotector by Eli Lilly for Alzheimer’s disease patients. Although the drug received a lot of media attention at certain points it hasn’t evidenced promise in Phase III trials to date. For example, Lilly terminated its EXPEDITION3 clinical trial for failure to meet its endpoint.
Recent news hasn’t fared well for the drug as it failed to achieve a targeted primary endpoint. Washington University School of Medicine in the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) Study conducted the analysis and reported that the experimental drug failed to meet its endpoint targets. However, Washington University and Lilly continue to analyze secondary endpoints and biomarkers and will present results at the Advances in Alzheimer’s and Parkinson’s Therapies (AAT-AD/PD™) Focus Meeting April 2020. So at this time Lilly declined to continue to pursue a submission for solanezumab in people with dominantly inherited Alzheimer’s disease. Moreover, the outcome doesn’t impact, according to Lilly, the ongoing A4 study.
The Investigator: Failure only Fuels Her Fire
Dr. Sperling, Director, Center for Alzheimer’s Research and Treatment at Brigham and Women’s Hospital doesn’t let the recent bad news concerning Alzheimer’s disease clinical trial failures get her down. In fact, the results “have fueled her fire,” reports WMC 5 Action News as she noted, “I think our research suggests we need to go earlier and we need to not give up hope, not back down, but in fact to double down and to work harder on this disease so that it does not defeat us.”
Representing the true nature of a clinical investigator, Dr. Sperling and others will not stop the research because of some bad news. They know breakthroughs don’t come easy or often. A relentless tenacity and commitment to the process discovery will prevail—it is a long-term struggle and they commit their lives to the battle. And hence other trials continue such as the AHEAD 3-45 trials (Eisai) and the APT Web study, which will help screen for future participants.
The Fight of our Life
As TrialSite News has discussed, the battle against Alzheimer’s is one that is personal for many and relevant to all. At the end of the day, when all is said and done all we will have is our memories. When a loved one passes that memory reconnects us with the feelings and emotions that make up our bond; our connection—our channel to remain linked and related–while we still live and the very last associations as we pass. If Alzheimer’s takes this from us, we not only don’t know our loved ones anymore but we don’t know ourselves. This is a horrific way to end what has been a miracle—each and every human life.
Despite recent failures companies such as Lilly and Biogen are commended for commitment and associated enormous investment to keep this fight going. And the investigators (and their support systems) on the front line of research, such as Dr. Sperling at Brigham and Women’s Hospital, that will someday make the breakthrough that leads to effective treatments. A recently approved treatment in China should be monitored—perhaps as the drug is commercialized real-world data will offer some insight into drug performance.
Since 1998, 146 drugs targeting Alzheimer’s have been tested and rejected. Presently there are an estimated 132 Alzheimer medications being tested in approximately 670 clinical trials worldwide. These studies generally fall into one of three categories of Alzheimer’s research including 1) Disease-Modifying Biologics, 2) Disease-Modifying Small Molecules and, 3) Symptom-Reducing Small Molecules. As one patient profiled in the recent WMC 5 Action News recently, Dennis Chan, a Boston-area computer scientist with a family history of dementia, declared “Losing what has been your self is a pretty scary thing.”
Dr. Reisa Sperling, Director, Center for Alzheimer’s Research and Treatment at Brigham and Women’s Hospital. Dr. Sperling also services as principal investigator for the Massachusetts Alzheimer’s Disease Research Center.