Today, US pharmaceuticals company Biogen and its Japanese partner Eisai announced they will cease clinical trials for an experimental treatment, known as aducanumab, for patients with mild cognitive impairment due to Alzheimer's disease and mild Alzheimer's disease dementia. In their announcement, the companies said they decided to discontinue the phase 3 trial after a "futility analysis" conducted by an independent data monitoring committee indicated the trials were unlikely to succeed.
Alzheimer's disease is the sixth leading cause of death among adults and affects an estimated 5.7 million Americans. Aducanumab is now the latest drug failure by large pharmaceutical companies in recent years during the late stages of testing.
I had hope for this study as it had some promising results in the earlier phases of clinical development, showing that the drug "hit its target" and was able to remove beta-amyloid from the brain of patients. It was also one of the first clinical trials to ensure that every patient participating had beta-amyloid plaques in their brains. The ADDF supported the first biomarker ever approved to diagnose Alzheimer's—the beta-amyloid PET scan—and we continue to invest in these critical tools.
While it seems obvious that you would want to make sure patients had such plaques if a treatment aims to remove them, that hasn’t been the case until recently. Researchers have instead used tests that measure "downstream" effects such as brain volumes on MRI, and cognitive outcomes like memory problems as criteria to enroll patients. Studies have indicated that up to 30 percent of those enrolled in previous clinical trials didn't in fact have plaques and possibly didn’t have Alzheimer's at all.
Despite identifying the right patients, aducanumab did not help the patients. Like many others, aducanumab targeted a compound in the brain known as beta amyloid. And so far, every drug that has been tested against it has failed. The current body of evidence indicates that targeting beta amyloid in senile plaques does not result in clinical improvement.
We need to continue to improve how we conduct clinical trials and find novel biomarkers to measure success early on in phase 2, because clinical trials are expensive and get increasingly expensive as they move from phase 1 to phase 3.
The goals are to weed out ineffective drugs earlier, sufficiently power trials to get useable data, and ensure patients in trials have the underlying pathophysiology a drug is designed to target. At the ADDF, we are working with investigators to build compelling clinical evidence of effectiveness using biomarkers in smaller phase 2 trials before proceeding to very expensive phase 3 testing, targeting novel pathways related to the neurobiology of aging.
Last July, the ADDF launched the Diagnostics Accelerator program through an initial funding commitment from philanthropists Bill Gates, ADDF Co-Founder Leonard Lauder, and others, including the Dolby family, the Charles and Helen Schwab Foundation, and the Association for Frontotemporal Degeneration. The Diagnostics Accelerator brings together philanthropic capital with a venture mindset to advance bold new ideas for easier and more accurate diagnosis of Alzheimer's disease and related dementias. The Diagnostics Accelerator was created to address the lack of biomarkers to easily and more specifically screen and diagnose patients, stage disease progression, monitor response to treatment, and improve the rigor and efficiency of clinical trials—critical to the development of effective drugs for the prevention and treatment of Alzheimer's.
Let's put today's news in perspective. Yes, there was a failure, and it is disappointing to patients, physicians, and the pharmaceutical companies involved. But in medicine and science, one clinical trial builds on another and gives us clues to help the next. Basic research on Alzheimer's started about 35 years ago. Today's breakthroughs in heart disease and cancer therapies are built on yesterday's investments in basic science. And so, will be the case with Alzheimer's disease.
Howard Fillit, MD
Founding Executive Director and Chief Science Officer
Alzheimer's Drug Discovery Foundation