M ore than 100 years after Dr. Alois Alzheimer first identified the disease bearing his name, there remains no cure.
But innovations in clinical trials, detection and potential treatments are pushing forward the next frontier of Alzheimer’s disease, the fifth leading cause of death in America.¹ The debilitating brain disorder destroys cognitive functioning skills—the ability to reason, remember, think, eat, and swallow.² In addition to its significant impact on patients and their loved ones, Alzheimer’s disease is one of the costliest conditions to American society—U.S. spending on Alzheimer’s disease and other dementias will cost an estimated $321 billion in 2022.¹
Anne White, senior vice president of pharmaceutical company Eli Lilly and Company and president of Lilly Neuroscience, has made it her personal mission to pursue innovation for patients and their loved ones. Fourteen years ago, her own mother passed away from Alzheimer’s. White was at her bedside, and held her hand through it. Now she is a leader at a company committed to Alzheimer’s disease research and development with a potential therapy based on more than three decades of work. We spoke with White about the next frontier of Alzheimer’s disease diagnosis and treatment, and the work to make treatment equitable and accessible for the communities most affected by the disease.
Alzheimer’s is a disease that many people are familiar with, whether through personal experience or pop culture. But it continues to be mysterious, and often, misunderstood. Tell us a bit about Alzheimer’s disease and why understanding it continues to be a challenge?
Alzheimer’s is such a relentless disease. It is one of the most feared diagnoses that people can get. People lose their memories, their independence and then their lives, so it is a long and painful journey that people go through. The fact is more than six million Americans aged 65+ are going to have dementia due to Alzheimer’s disease, and that is predicted to double by 2050 and stunningly, nearly two-thirds of Alzheimer’s disease patients are women. There are also racial and ethnic disparities to consider.
Another thing that we face is helping people understand that Alzheimer’s disease is not a normal part of aging. I still sometimes hear people say, ‘Well, you’re always going to have these cognitive issues as you get older.’ And certainly, some of that does happen as part of the aging process, but it is not the same as Alzheimer’s disease. This is very, very different.
And not all patients with Alzheimer’s disease are incapacitated or require 24/7 assistance. Patients with mild cognitive impairment—the earliest symptomatic patients—may be mobile and capable. But they urgently need diagnostic support and possibly treatment with innovative medicines (in clinical trials or real-world) to potentially slow the progression of the disease and delay more advanced Alzheimer’s disease symptoms for as long as possible.
How often are people misdiagnosed with Alzheimer’s disease?
The statistics of misdiagnosis are alarmingly high, particularly in Black and Hispanic patient populations. In some of our earlier clinical trials, as many as one-third of the patients in a trial did not have Alzheimer’s or Alzheimer’s disease pathology, but had strokes, some other type of vascular dementia, or other issues that caused cognitive symptoms. When I hear people say, ‘There’s never been any success in Alzheimer’s, so why do you believe that you will see success?’ Well, we have learned so much, and that learning is why I am so hopeful about the future.
What are the benefits of timely detection?
A timely and accurate Alzheimer’s disease diagnosis is really important, and the challenge today is that there’s often no diagnosis, a delayed diagnosis or an incorrect diagnosis. What we found is that the potential to delay the progression of Alzheimer’s disease may lie in detecting and treating earlier than we do today.
The pathology of this disease is caused by the accumulation of amyloid plaques in the brain, which over time, leads to the development of tau neurofibrillary tangles, which contribute to the death of brain cells. This process can begin 20 years prior to the diagnosis of AD. The goal is to develop medicines that impact this accumulation as early as possible to slow disease progression. Our ultimate goal is to determine if we can attack these plaques before patients even exhibit symptoms.
We’re also working on medicines that target both amyloid and tau pathology, and we may learn that a combination of such medicines might actually do a better job targeting the underlying pathology of this disease.
Let’s talk about progress and innovation. What are some of the challenges you face in the Alzheimer’s disease space when it comes to research and development (R&D)?
Probably the biggest challenge is the rate of clinical trial enrollment and completion. This is a very difficult disease for patients and loved ones, and it can be a challenge to consistently come into the office for the trial. Having my own experience with Alzheimer’s disease, I know that these trials are unique in that they require not just the person with Alzheimer’s to be part of the trial, but a study partner as well. A big part of the assessment is the study partner telling us how the patient is doing.
Additionally, medical innovation happens through clinical trials—but low participation of underrepresented populations continues to be a long-standing problem in our industry. To combat this, specific outreach strategies are needed to ensure equal access. We also need to build trust between researchers and racial/ethnic minority groups who may be skeptical or even mistrustful of medical research, due to historical discrimination in medicine and barriers to accessing quality healthcare.
Although we can look at the results of our clinical trials to understand their potential benefit, we need to have confidence in understanding that patients from diverse backgrounds will equally benefit from such treatments. We must work to make trials as easy as possible to participate in.
What are some of the steps that you are taking at Lilly to combat that type of inequity in medicine? How successful have those efforts been?
One of the areas of focus for us is just driving increased minority group enrollment in our trials—we believe that will provide a lot of information about how these medicines can help a diverse population. For an ongoing Phase 3 trial called TRAILBLAZER-ALZ 3, we have expanded beyond traditional brick and mortar sites. We have utilized what we call mobile research units equipped to educate, and conduct screening procedures, including blood draws, lab sample processing and data collection. The combination of a decentralized trial for a potential Alzheimer’s disease therapy, and an investigational screening blood-based biomarker diagnostic means that we can utilize our mobile research units going to communities where patients live. This greatly expands our ability to move quickly and recruit patients from a diverse population.
In TRAILBLAZER-ALZ 3, participants can also complete many study activities, including clinical interviews and cognitive testing, via virtual appointments using a study tablet in a convenient location for the participant. In addition, any materials that we provide to communities go through health literacy review to ensure cultural competency. We are hoping these new approaches will impact our ability to get a more diverse population in our trials than what we have had in the past.
Do you think part of the reason that it has been so difficult to get to a point where Alzheimer’s treatment is accessible is because the technology was not available?
I do think the innovation that we have seen over the past few years has made a huge difference in the space. I am so impressed with the progress that we have made in diagnostics. When my mom died from Alzheimer’s 14 years ago, she was diagnosed with an autopsy–that was the only definitive diagnosis that you could have of Alzheimer’s at the time. We now have positron emission tomography (PET tracers) that have really changed the field dramatically, and they have been the gold standard used to determine whether people have Alzheimer’s pathology in their brain. And, blood tests are also being developed to aid in the diagnosis as well.
Why is now an opportune time to dive even deeper into Alzheimer’s, and are you hopeful that in the next 10 years or so, there will be even bigger advancements made?
I do think that the momentum we have got now is incredibly exciting. With every study we do, and with every answer that we get, whether positive or negative, it further informs the work we do in the future. I am particularly excited by what we have learned from our recent trials with one of our investigational products that targets amyloid plaque. Hopefully, we are on the cusp of some significant potential steps forward, even in the next year.
As you look at our neurodegeneration pipeline [medicine and research focused on neurodegenerative diseases], our understanding of Alzheimer’s disease has also allowed us to tap into disease modifying therapies that could potentially help with other neurodegenerative disorders. We are focused on ALS (amyotrophic lateral sclerosis), Parkinson’s disease and Huntington’s disease—all of which also have huge unmet needs. Understanding Alzheimer’s and how the brain pathology works, and how medicines like ours have been able to impact that, has given us some real insights into some of these other difficult-to-treat diseases. And that does make me very hopeful.