By Wendy Diller
2023 was a historic year for battling Alzheimer’s disease. After decades of dismal progress, treatment now has a plethora of firsts: Eisai / Biogen’s Leqembi, the first fully FDA-approved drug that slows disease progression; the first Medicare policies covering the costs of that drug and withdrawal of a restrictive Medicare policy covering PET imaging for Alzheimer’s, and the first proposed Medicare pilot project, called the GUIDE Model, aimed at improving quality of care for people living with dementia and reducing strain on caregivers.
An army of people—patients, caregivers, and experts—are responsible for these wins. Among their most influential leaders is the attorney and philanthropist George Vradenburg, who with his late wife Trish, co-founded UsAgainstAlzheimer’s in 2010. Led by Vradenburg, the organization has raised public awareness of brain health and preventive behaviors that can reduce risk of dementia and pushed for policy and reimbursement changes affecting nearly every corner of the Alzheimer’s world. His passionate sense of urgency and holistic, team-oriented approach to identification of roadblocks and finding pragmatic solutions seems to be paying off, if not quite in the 2020 timeframe he set for finding a cure when the organization started out on this journey.
His reasons for involvement were personal. The disease had already affected three generations of his family and “will hit my children and grandchildren if we don’t make more progress in the next 20 years,” Vradenburg says. “We run to the problem, rather than follow it. I would like to have this disease cured and get out of this job.”
Alzheimer’s disease is the sixth leading cause of death in the United States, affecting 6.7 million people over 65 years old, of whom two thirds are women.
That number is projected to increase to 12.7 million by 2050 as the population ages. Further, as advocates point out, the Alzheimer’s population isn’t just patients—some 85 million Americans have families or friends with the disease. Despite the large numbers, when Vradenburg started on this crusade, the disease was by all accounts neglected, due largely to years of disappointing failures in drug development and the lack of adequate tools for tackling it. The National Institutes of Health (NIH) budget for Alzheimer’s R&D was $448 million annually, clinical trials of new drugs took a decade or longer, with dismal results, and awareness among the public of different kinds of dementia was minimal. Patients and families had little to look forward to, Alzheimer’s disease was the only top 10 deadly disease without an effective treatment, and a national strategy to combat the disease, along the lines that existed for cancer and HIV, did not exist.
Today, the National Institute of Aging (NIA) budget for Alzheimer’s and related dementia research is $3.7 billion, Leqembi is on the market as of July 2023, with the FDA approval of a second disease-modifying drug expected by early 2024, and the US has an official blueprint for advancing care and treatment (The National Plan to Address Alzheimer’s Disease).
Vradenburg and experts are the most optimistic they’ve ever been about the future, and, as a reflection of that mindset, Vradenburg is betting a vaccine that prevents disease onset could become available by 2030. Meanwhile, he says, Leqembi’s commercialization and the likely near-term launch of Eli Lilly’s donanemab are the result of a better scientific understanding of the pathology. “Because of these approvals of this first round of drugs, [many more] biotech and pharmaceutical companies can see a path to market,” says Vradenburg, adding that “investors now see that with the right regulations and coverage policies, this work can be enormously rewarding.”
UsAgainstAlzheimer’s role in this fight is to bring all relevant stakeholders to the table and create opportunities for them to tackle specific bottlenecks at every point of the care continuum. It is in effect “a convener and a market maker,” says Vradenburg. By tapping the breadth of the Alzheimer’s community, which includes people from all walks of life, including those who hold the power to initiate change, it has succeeded in:
Persuading Congress to dedicate billions of additional dollars to NIH funding for Alzheimer’s research. Vradenburg estimates that the additional funding cumulatively totals billions of dollars over the past decade.
Ensuring that the FDA evaluates Alzheimer’s drugs using the accelerated approval process, which allows the agency to give approval to certain drugs based on Phase 2 data on the condition that sponsoring companies eventually provide Phase III data necessary for full approval.
Urging the Centers for Medicare & Medicaid Services (CMS) to withdraw Medicare’s policy limiting PET scans to once in a person’s lifetime. Thus, the agency for the first time, in October said it would cover the cost of repeated PET scans that are crucial for early detection and monitoring of Alzheimer’s disease because they can identify the presence and progression of amyloid plaques and tau tangles in the brain. Amyloid plaques and tau tangles are key indicators of Alzheimer’s progression and therefore necessary to evaluate the effectiveness of the new therapies.
Advocating for Medicare’s GUIDE pilot program, which experts call a “game- changer” because for the first time it would cover qualifying healthcare systems and physicians to provide certain levels of care to families and unpaid caregivers to help patients stay home.
As an example of some of the behind- the-scenes work it has done: The Global Alzheimer’s Platform Foundation (GAP) it founded to create a network of specialized clinical research sites addresses one of the organization’s priorities: facilitating clinical trials, which currently can take decades to complete. Its work has resulted in faster initiation and six to nine months earlier completion of trials on average than non-GAP trial timelines. About 15 to 20 trials to date have used the platform, some of which are in progress, and others, including Leqembi, which are completed.
Scientists now believe that damage from Alzheimer’s begins well before symptoms appear. UsAgainstAlzheimers is also fighting for new tools for earlier detection and diagnosis of the disease, so that drug interventions now coming to market can be used earlier in the course of the disease, when they are most effective.
A lot of excitement around these new technologies relates to advances in digital and blood-based biomarkers, along with the potential of AI to address weaknesses in the fragmented, under-resourced US healthcare system, which is ill-equipped to manage the rollout of a complicated new medicine that is the first of its kind in ways that ensure equitable access to care for a large patient population. Most people with Alzheimer’s will not qualify for the new drugs, at least in the first- generation. Identifying those who fit the eligibility criteria will require education of clinicians and patients, along with the use of new technologies that can rapidly, inexpensively, and accurately assess whether the mild cognitive impairment that is common in older people is related to Alzheimer’s.
A working group of business leaders, the Global CEO Initiative on Alzheimer’s Disease, which UsAgainstAlzheimer’s founded in 2013, aims to break down these barriers to access in several ways, including pressing for policy changes that could accelerate adoption of digital screening technologies, which are coming online and could be in the training and organization.
Ultimately prevention is the last frontier, and Vradenburg believes that a vaccine to prevent Alzheimer’s is closer to market than many people realize—he tends, unsurprisingly, to be an optimist. A consortium organized by UsAgainstAlzheimer’s is taking an ‘Operation WarpSpeed’-like approach to making that happen. Lots of uncertainties lie ahead, but Vradenburg envisions a template for offering a vaccine would be like administration of the shingles vaccine: starting at a certain age, well in advance of symptomatic onset, it could be recommended for everyone, with periodic boosters.
“This isn’t just theoretical—a vaccine is already in Phase 2 clinical trials, and I look forward to the day when we cut the costs of interventions in this disease by a factor of 10 or more, and basically reduce the costs to Medicare for caring for people with this disease because we’ll be able to prevent it,” he says.
Finally, public awareness of brain health and preventive behaviors that can reduce risk of dementia are on the organization’s agenda, with robust programs to educate families and hold businesses accountable for encouraging lifestyle and behavioral changes that improve brain health. As an example of the organization’s creativity, it is building a scorecard for employers to adopt that tracks their progress in promoting brain health and measures the impact of those programs on improved financial performance of companies and, more broadly, of US competitiveness in the world.
With recent wins, Vradenburg’s passion for this work has only intensified. “I think we’ve nicked the beast,” he says, “There is good reason to be excited–and those of us in the trenches are–but there is still so much more to be done before we can say we’ve won this important battle.”