This year tested us like no other, but from great challenges came innovation and creativity as we drove forward our mission to identify new therapies to prevent and treat Alzheimer’s disease.
In-person events were reimagined as virtual events that gave us new ways to unite as a community and support vital research. As researchers faced the task of keeping clinical trials, as well as biomarker and drug development programs, going, the ADDF was there to provide guidance, advice, and flexibility in our support.
In large part due to our remarkable donors, supporters and researchers, 2020 turned out to be a great year for Alzheimer’s research, with the ADDF investing $77 million to date to support over 100 active research programs.
First Alzheimer’s Blood Test Available and More Biomarkers to Come
If you asked me five or ten years ago if there would ever be a blood test for Alzheimer’s disease, I would have been skeptical. So the fact that there is now an Alzheimer’s blood test on the market is just amazing. Investments from the ADDF were instrumental in helping C2N Diagnostics launch the first ever commercially available blood test to help with early Alzheimer’s detection and diagnosis. Using just one teaspoon of blood drawn from the arm, PrecivityAD™ can correctly identify brain amyloid plaque status, a primary marker of Alzheimer’s disease, in 86% of patients. A second blood test is expected to enter the market as early as 2021, which will measure levels of p-tau217 and can accurately distinguish Alzheimer’s from other neurodegenerative disorders, as well as correlating with the stage of the disease.
The ADDF’s Diagnostics Accelerator (DxA) held a meeting in October with funded investigators sharing updates about the exciting work happening across the globe. The DxA continues its strategic investment in research aimed at developing reliable, affordable and easy to use biomarkers, particularly blood tests, as well as eye scans, and the latest frontier, digital biomarkers.
First-Ever Disease-Modifying Drug for Alzheimer's Reviewed by FDA Panel
In November, an independent FDA advisory committee signaled in several votes it does not believe the clinical study data for Biogen’s aducanumab supports the drug’s approval for patients with early-stage Alzheimer’s disease. The FDA’s final decision, which does not always follow the recommendation of the independent committee, is expected early this year.
Whatever the final decision may be, one thing is certain: the aducanumab clinical trial was a landmark trial that moved the field forward by being one of the first to use a biomarker test to enroll patients with Alzheimer’s disease. By screening participants with Amyvid™, an amyloid PET imaging test that was developed with early support from the ADDF, investigators were sure they were enrolling patients who had amyloid plaques in the brain, a hallmark of Alzheimer’s and the target of aducanumab. Importantly, the Amyvid™ test showed that aducanumab worked in removing these plaques from the brain.
As we’ve long believed, aducanumab, or any single drug, is unlikely to be a magic bullet. The goal is to develop drugs that work on many different pathways, including those beyond amyloid, that are implicated in Alzheimer’s disease. There are more than 100 drugs currently in clinical trials that address different targets, including misfolded proteins, inflammation, vascular problems, genetic mutations, and age-related changes associated with Alzheimer’s. And we saw some promising results this year.
Promising Clinical Trial Results: Repurposed Drugs Front and Center
The ADDF’s comprehensive approach to Alzheimer’s research not only focuses on innovative new drugs and targets, but also on research into repurposing existing drugs. Repurposing drugs that have already been approved by the FDA for other diseases means researchers can save time and money by proceeding directly to human clinical trials with Alzheimer’s patients because the drugs’ safety is already established.
- During our 21st International Conference on Alzheimer’s Discovery, Ana Pereira, M.D., of the Icahn School of Medicine at Mount Sinai in New York, reported study results for rilozule in patients with mild Alzheimer’s disease. Patients treated with rilozule, which is thought to modulate levels of a neurotransmitter in the brain called glutamate, had significantly less decline in cerebral metabolism, which is strongly correlated with cognitive performance.
- In a study published in July, Giacomo Koch, M.D., Ph.D., and colleagues at the Santa Lucia Foundation in Rome reported that rotigotine, which works on the brain neurotransmitter dopamine, improved cognitive function in patients with mild-to-moderate Alzheimer’s.
- In a study published in May, researchers from Georgetown University Medical Center reported that nilotinib had a modest effect on reducing two biomarkers of Alzheimer’s—beta-amyloid and tau—measured in spinal fluid or by brain PET scans. Nilotinib is thought to work by turning on the “garbage disposal” machinery inside neurons to get rid of these toxic proteins.
Rilozule has been used for more than 20 years in patients with amyotrophic lateral sclerosis (ALS; also known as Lou Gehrig’s disease) and is the only drug shown to slow its progression. Rotigotine is approved to treat symptoms of Parkinson’s disease and nilotinib is used to treat leukemia in children and adults. In each case, investigators are exploring phase 3 studies of these drugs in Alzheimer’s and related dementias.
We also eagerly await another exciting trial readout, expected in the first half of 2021. We are currently funding the PEGASUS trial, which is exploring a two-drug combination to prevent nerve cell death and degeneration in people with Alzheimer’s disease. This is the first trial to target two novel Alzheimer’s mechanisms at once. The drug used in this trial, AMX0035 from Amylyx Pharmaceuticals, has already shown clinically significant benefits in a trial of patients with ALS.
Growing Evidence for Benefit of Prevention and Brain Health
In 2020, we reported on the latest finding from the Lancet Commission, which said targeting 12 risk factors throughout life may delay or prevent up to 40% of dementia cases. The Commission added three new risk factors to its list in 2020: traumatic brain injury, air pollution and excessive alcohol consumption. Providing credible, science-based strategies to promote brain health and/or prevent Alzheimer’s disease is the focus of our dedicated website, Cognitive Vitality.
Earlier, we launched Cognitive Vitality Reports, a new resource of more than 200 reports for researchers and clinicians evaluating the effect of drugs, drugs in development, supplements, nutraceuticals, food and drink, and non-pharmacologic interventions that have potential benefit or harm for brain health. This resource can also assist healthcare professionals in making informed decisions about the safety and efficacy of each intervention available to aid cognitive health.
Half of the clinical trials in the ADDF’s portfolio are aimed at slowing the progression of mild cognitive impairment and preventing dementia. The ADDF continues to support work that translates the biology of aging, the single biggest risk factor for dementia, into new ways to treat and prevent Alzheimer’s disease.
Venture Philanthropy Scores Major Successes
The ADDF’s venture philanthropy model casts a wide net to identify and invest in a diverse portfolio of drug and biomarker targets that reflect the various biological pathways involved in neurodegenerative dementias. Our rigorous due diligence process evaluates the drug or technology, supporting data, potential clinical impact, proposed commercial path, and development teams, so it is no surprise when our investments pay off. Here are the year’s highlights:
- Cognition Therapeutics was awarded more than $75M from the National Institutes on Aging for its clinical trial program of a neuroprotective drug, currently in phase 2 trials, that has disease slowing and possibly disease preventing properties.
- Tetra Therapeutics announced a merger with Shionogi, a major research-driven pharmaceutical company, a $500M deal to develop Tetra’s portfolio of products for the treatment of brain disorders associated with cognitive and memory deficits.
- Vanderbilt University entered a $515M licensing agreement with Acadia Pharmaceuticals to advance its drug into phase 2 clinical trials. The drug has cognitive enhancing and potentially neuroprotective properties.
- Athira Pharma raised $85M in private investment, primarily for a phase 2/3 research program of its neuroprotective drug in clinical development.
Each of these companies has one thing in common—early investments from the ADDF. A key feature of our venture philanthropy approach is our high level of engagement and long-term commitment to our partners. The ADDF provides not just important capital, but also guidance on preclinical and clinical development, strategic alliances (or collaborations and partnering opportunities), and other fundraising sources. The 2020 successes are good for the portfolio programs, the ADDF, which gets a return on its investments to reinvest in promising science, and most importantly, the millions of patients living with Alzheimer’s and their families who eagerly await the treatments research will bring.
I hope after reading about the exciting progress of 2020, you share my optimism about what 2021 will bring. I wish each one of you a year of much health and happiness!