First new Alzheimer’s treatment approved in 17 years, two more get breakthrough designation for FDA review
The FDA approved aducanumab (Aduhelm®), an antibody that clears amyloid plaques from the brain, in June. The jury is out on just how much aducanumab slows cognitive decline, but in the interim, this gives patients and their families the ability to decide if the drug is right for them. Importantly, the FDA also sent a clear signal by using an accelerated approval pathway for aducanumab that biomarker measures, in this case clearance of amyloid brain plaques, will be considered for Alzheimer’s drug approvals.
The FDA seems intent on getting innovative new therapies to Alzheimer’s patients as quickly as possible. More evidence of this is the breakthrough therapy designation it granted for two more amyloid clearing drugs. Lecanemab and donanemab also work by removing toxic amyloid deposits in the brain. We should know more soon because one manufacturer has already begun presenting data to the FDA and the other is expected to follow suit in 2022.
More than three in four drugs in the Alzheimer’s research pipeline take non-amyloid approaches
Amyloid deposits in the brain have long been a focus of Alzheimer’s research, so it stands to reason amyloid-focused drugs are the first to come to market. But the ADDF has long advocated the biology of aging theory, which maintains that amyloid is just one of many targets in the aging brain that lead to Alzheimer’s. The theory, now widely accepted, is reflected in an incredibly diverse drug pipeline.
The ADDF Clinical Trials Report, issued in November, shows just how far beyond amyloid today’s research pipeline goes. Our report outlines hundreds of treatments being tested for Alzheimer’s disease, including nearly 120 that hold promise not just for managing symptoms, but actually slowing and even stopping Alzheimer’s progression. These drugs target at least eight unique pathways implicated in Alzheimer’s disease, from inflammation to vascular disease, genetic changes and more.
An ADDF-funded study targeting one such unique pathway was published in Brain with a successful phase 2 read out reporting that riluzole, a drug that has been used for more than 20 years to slow the progression of ALS, was shown to slow brain metabolic decline and have a positive effect on cognitive performance versus placebo in people with mild Alzheimer’s disease.
Alzheimer’s researchers are rapidly validating new biomarkers, including the first ever blood test now available in doctor’s offices
In the words one of my colleagues, the sheer volume of talks discussing biomarkers for early detection of Alzheimer’s was “staggering” at this year’s Alzheimer’s Association International Conference (AAIC), as well as being a key theme at the ADDF’s International Conference on Alzheimer’s Drug Discovery and the Clinical Trials on Alzheimer’s Disease (CTAD) conference.
Clinical trials are incorporating biomarkers in new and innovative ways, helping researchers connect what’s happening inside the brain with clinical improvements in cognition and memory. The Amyvid® PET scan, which also benefited from ADDF funding and was instrumental in the approval of aducanumab, is being used in ongoing studies. Drugmaker Eli Lilly is using both Amyvid and Tauvid®, which measures tau levels in the brain, as biomarkers in its donanemab trial, Trailblazer-AD.
Biomarkers have even broken through to clinical practice. The PrecivityAD™ blood test, which received early funding from the ADDF, is 81% accurate in predicting amyloid levels in the brain. The test can be ordered in doctors’ offices in 49 U.S. states. The SYNTap biomarker test also launched for commercial use in the U.S. in late 2021. This test detects aggregates of alpha-synuclein protein in spinal fluid, a hallmark of Alzheimer’s and other brain diseases. Through the Diagnostics Accelerator, the ADDF provided funding to Altoida, which was awarded U.S. FDA Breakthrough Device Designation for the Neuro Motor Index, a predictive system for early diagnosis of Alzheimer’s disease.
Fascinating research reports on new ways that could lower the risk of developing Alzheimer’s
With 6 million Americans and 55 million people already living with Alzheimer’s worldwide, the search for treatments to help them is vital. But half of the trials in the ADDF investment portfolio are focused even earlier—on preventing the disease in the first place. This year we awarded the Melvin R. Goodes Prize to Dr. Miia Kivipelto for her groundbreaking work on the world’s first global initiative for prevention of dementia and Alzheimer’s disease.
In addition to our direct investments in prevention research, our Cognitive Vitality website continued its important work evaluating ways to improve brain health. In 2021 alone, ADDF scientists completed 10 ratings of prevention interventions and posted 17 blogs to help the public maintain its brain health.
We also tracked and reported on exciting, and often surprising ways we might prevent Alzheimer’s. Your morning coffee, for example, may also protect brain health. ADDF-funded researcher Dr. Cecilia Lee reported that patients who undergo cataract surgery lower their risk of dementia by 30% compared to those who do not.
A study in Nature Aging reported that taking sildenafil, a drug better known as Viagra, is associated with a nearly 70% reduced risk of developing Alzheimer’s. The results came from an analysis of a very large insurance database, so we need much more research to tell if it really is a direct relationship between the drug and dementia reduction. But there is a biological reason to believe this association is true. Sildenafil works by relaxing muscles and increasing blood flow, which could explain its potential benefit in the Alzheimer’s brain.
Venture philanthropy model with the rigor of venture capital investments continues to lead the way
Alzheimer’ disease is an emerging and growing area of interest in the biotech field. To date, the ADDF has invested more than $168 million in over 650 research programs including 110 biotech programs. We focus our investments in innovative new areas with high unmet need. That means, as with all drug development, many ideas will not advance. But those that do bring us financial returns which go right into the next great research idea, and of course give hope and new treatments to those who need them. Our investments catalyze critical inflection points for biotech and academic researchers, such as our long-term investment in Cognition Therapeutics, which completed its initial public offering this year, and Vanderbilt University, which entered a $515 million licensing agreement with Acadia Pharmaceuticals to advance its cognitive enhancing, potentially neuroprotective drug into phase 2 clinical trials.
Looking ahead
For 23 years, the Alzheimer’s Drug Discovery Foundation (ADDF) has been a major driver of innovation and change in Alzheimer’s drug discovery and development. Our leadership has helped expand the scientific understanding of the biology of aging that leads to Alzheimer’s disease and has played a key role in many of the most exciting advances of the last year.
Even as the COVID pandemic continued to test all of us in 2021, the foundational depth and strength of Alzheimer’s research worldwide fueled more good news than ever, with the promise of even more to come in the next year.
As we start off 2022, we’re more optimistic than ever that the next few years of scientific advancement will bring more diagnostics and treatment options to Alzheimer’s patients and their families. As ADDF supporter Bill Gates noted this past year, “I have never been more optimistic about the progress being made in Alzheimer’s research, and the breakthroughs that may someday soon let us substantially alter the course of the disease.”