News from the Memory and Aging Program at Butler Hospital
December 8, 2022
There were four major announcements made at the Clinical Trials on Alzheimer's Disease annual conference (held November 29th through December 2nd), making it an exciting and historic meeting for the field of Alzheimer's research. The announcements were related to exciting new findings and clinical trial results for the treatment and detection of Alzheimer's. All have links to Rhode Island researchers (including those at the Memory and Aging Program at Butler Hospital) highlighting the state as an innovative and collaborative hub for world-class Alzheimer's research.
Perhaps the most poignant moment of the conference came late in the day on November 29, when pharmaceutical company Eisai presented the results of the Clarity AD trial, which showed lecanemab to be the first drug to achieve substantial amyloid lowering with a clear clinical benefit. The results were presented at the very moment that the New England Journal of Medicine officially published the results, followed quickly thereafter by an article in the New York Times, all of which served to underscore the significance of the results in the fight to end Alzheimer's.
Here's a brief look at the details of the lecanemab announcement as well as each of the other three major announcements, along with their connections to The Memory and Aging Program (MAP) at Butler Hospital and other major centers of Alzheimer's research here in Rhode Island.
Pharmaceutical companies Eisai Co., Ltd. and Biogen, Inc. shared the full results of the Clarity AD clinical trial, a global, Phase three confirmatory trial of the drug lecanemab (BAN-2401) for the treatment of early Alzheimer’s disease (AD). The results showed the drug slowed cognitive decline by 27% on the global cognitive and functional scale, and slowed decline of activities of daily living by 37%. (See full study results here.)
Butler Hospital’s Memory and Aging Program (MAP) and Rhode Island Hospital’s Alzheimer’s Disease and Memory Disorders Center are among the research sites that carried out the Clarity AD study and are currently enrolling participants for another study of lecanemab, called the AHEAD Study.
“The results of the CLARITY trial represent an important step forward in the fight against Alzheimer’s disease,” said Stephen Salloway, MD, MS, founder of the Memory and Aging Program at Butler Hospital, Martin M. Zucker Professor of Psychiatry and Human Behavior, Professor of Neurology, and Associate Director of the Center for Alzheimer’s Disease Research at Brown University. “The study is the first completed pivotal trial to show amyloid-lowering and clear clinical benefits providing new hope for patients dealing with early stages of the disease. We are very proud of the role that Rhode Islanders played in making this advance possible, and we eagerly await review by the FDA and the Center for Medicare and Medicaid Services. The goal is to roll this new medication out safely and to find combination treatments that build on these positive outcomes.”
The U.S. Food and Drug Administration (FDA) is expected to announce a decision on whether to grant accelerated approval for lecanemab by January 6, with a decision on accelerated approval for donanemab (see below) expected at the same time or soon thereafter.
Eli Lilly announced the results of a six-month trial comparing donanemab to aducanumab (Aduhelm) using data from its ongoing TRAILBLAZER-ALZ 4 study, a Phase 3 trial of donanemab (a study also conducted at Butler Hospital). The results showed that donanemab reduced brain amyloid plaque levels by 65.2% at six months compared to baseline, while Aduhelm reduced levels by 17% for the same time period.
Dr. Salloway presented the findings at the conference, says he is encouraged by the findings.
“What's encouraging here is we’re comparing one drug that's already been approved and another drug that’s being considered for accelerated approval, and it looks like donanemab lowers amyloid plaque significantly more in six months than you can imagine under the current dosing regimen recommended by the FDA. And it appears to do that safely,” Dr. Salloway said.
Donanemab is being studied in a Phase 3 trial called TRAILBLAZER 2, the results of which are expected to be announced in the spring.
Pharmaceutical company Roche shared that its investigational medication, gantenerumab, failed in both of its Phase 3 clinical trials, GRADUATE I and II. As reported in coverage of the CTAD presentation by Biopharma Dive:
"After one year of treatment, gantenerumab reduced amyloid burden in patients only half as well as the trials’ designers had expected based on previous research, said researcher Randall Bateman, a neurology professor at Washington University in St. Louis who helped lead the studies. Moreover, around half as many gantenerumab patients as predicted tested negative for amyloid over the course of the trial. Almost none tested negative after one year of treatment, and only around a quarter did after more than two years, researchers revealed."
But even negative results bring some positive momentum, as researchers now study the reasons behind why lecanemab and aducanumab both produced better results than gantenerumab.
"These are disappointing top-line results from a well-run trial," Dr. Salloway said in an article by ALZFORUM. "We need to evaluate the safety and efficacy for each compound in this class and learn as much as we can from each study. There appears to be a small clinical benefit with gantenerumab that did not reach statistical significance, and a lower-than-expected amount of amyloid reduction. It will be important to determine whether those who became amyloid-negative on PET had a larger clinical response, and whether treating with a higher dose could be safely instituted to produce greater efficacy."
CTAD 2022 also included a great focus on the ongoing and future development of blood biomarkers for the detection and treatment of AD. Advancements in this space could lead to the discovery of additional or more efficient means of detecting and treating Alzheimer's, as well as an improved means of measuring response to treatment. In addition to amyloid beta plaques (the focus of current major studies in this space) other targets for study include tau proteins and neurofilament light chain.
MAP is currently conducting several studies involving biomarkers, including AHEAD, ADNI-3, LEADS, and most recently and significant, Bio-Finder Brown.
There's also a new blood test, PrecivityAD-2®, that is already FDA-approved and is just starting to come into clinical use. The test measures the presence of amyloid and phospho-tau in the blood, which is strongly predictive of the presence of amyloid in the brain. The availability of this test is especially exciting for research because it will allow for easier and more efficient pre-screening for eligibility of potential study participants without the need for as many PET scans.