STATE OF ALZHEIMER’S RESEARCH HAS ADVANCED SIGNIFICANTLY
Several years ago, at a research conference for Alzheimer’s disease and Parkinson’s disease, there was a screening of the documentary, “Turning Point.” The video describes the journey of researchers and patients who were part of Eli Lilly’s Alzheimer’s clinical trials for a drug called Solenezumab. After hundreds of millions of dollars and decades of work, the drug ultimately failed to slow cognitive decline, and halfway through the last step of testing in a phase 3 trial, to see how safe and effective the drug was in several hundred patients, everything was halted. Patients who were part of the trial were understandably devastated, but the part of the story that has stayed with me most strongly was of Dr. Reisa Sperling, a researcher who had worked on the drug for years.
When Sperling began, her father was healthy, but he was eventually diagnosed with Alzheimer’s, and he continued to decline, ultimately dying from the disease that she was actively trying to cure. Imagine how heartbreaking it was to be powerless to save her own father when it was literally her job.
Now imagine thousands of researchers and patients and hundreds of failed dementia drug trials. That had been the reality from the time that the last Alzheimer’s drug had been approved in 2003.
While Solenezumab’s failure was a mere six years ago, the state of Alzheimer’s research has changed in several remarkable ways. First, even though the drug targeted amyloid plaques — which, along with tau tangles, are the hallmark of Alzheimer’s disease — when those trials began there were no biomarkers to effectively measure how well the drug reduced plaques, or even to determine whether every participant in the trial was accurately diagnosed with Alzheimer’s in the first place.
Now, not only are we able to use positron emission tomography (PET) scans to see plaques and tangles in the brain, but there is a blood test cleared by the Food and Drug Administration to indicate the likely presence of disease.
Second, drug development for many years was dominated by drugs that target amyloid, with the expectation that reducing plaques or plaque production would change the course of disease and ultimately improve cognition. Indeed, six years ago, approximately 75 percent of disease-modifying drugs in Phase 3 were focused on amyloid; today that number is less than 30 percent, with a more diverse array of drug targets, including those addressing tau, inflammation, protection of neurons and metabolism. Likewise, the total number of drugs in trials increased from 93 to 143. The most profound developments, however, have been the FDA approval of a disease-modifying drug and more recently positive results of another phase 3 trial from Eisai and Biogen.
The increase of drugs in the pipeline and recent success has not been by accident. While the incidence of Alzheimer’s disease is greater than breast cancer and colon cancer combined, the funding has historically paled in comparison. Fortunately, National Institutes of Health (NIH) funding for Alzheimer’s and dementia research by the NIH has quadrupled over the last 10 years to $3.2 billion, an increase that is greater than any other disease area over the same period. The Alzheimer’s Association is investing more than $310 million in global research, including a significant amount in San Diego, one of the largest dementia research hubs in the U.S., and is active in advocacy to increase government funding for Alzheimer’s research.
So what’s next for Alzheimer’s research? The research community is anticipating more detailed results from the Eisai/Biogen trial at the Clinical Trials in Alzheimer’s Disease Conference in San Francisco on Nov. 29. Researchers — including me — will learn how likely the drug is to deliver on the promise of slowing cognitive decline, allowing people to keep their independence for six months or longer, and if the drug works better in specific groups of patients.
These functional differences matter to patients and their families, but it’s just a start. In the next few months and years, we’ll also hear the results of other amyloid drugs and drugs targeting different aspects of biology. Researchers continue to assess whether therapies have the potential to not just slow decline but prevent disease in the first place, and assess which drugs are more powerful in combination than alone.
Likewise, there’s significant investment in understanding other behavioral and lifestyle factors that can prevent disease, and understanding variation in the development of disease in people from different backgrounds. This disease is complex, and it’s being tackled from all possible angles.
Researchers are tenacious and personally affected. I’m extremely hopeful that the effort, investment and attention will finally deliver some big wins.