Challenges and Opportunities

The last mile—in consumer and packaged goods—refers to the end of the supply chain when a product is finally transported to the customer's doorstep. While large retail companies such as Amazon have mastered this step, the last mile is particularly challenging to achieve in drug development and health system transformation. On average, the transition from approval to standard-of-care takes between 17 to 20 years; when considering a progressive neuropathological disease like Alzheimer’s disease (AD), the cost of waiting this long is fatal. As Dr. Phyllis Barkman Ferrell—a consultant, investor, and Chief Impact Officer at Startup Health—explained this dilemma, she highlighted one of the primary issues in the Alzheimer’s disease drug development sector: delivery. Not only has it been a challenge to put innovations through the regulatory approval process, but getting those treatments to patients has also been a major hurdle. Dr. Ferrell’s insights as a consultant working with organizations ranging from non-profits to startups to larger biotech companies illuminated some of the key scientific, systemic, regulatory, and research-related challenges in the Alzheimer’s disease sector along with a sense of hope for the future of the industry.
Alzheimer's disease research began with Alois Alzheimer, a German physician who first described the disease in 1906 after studying a patient who exhibited memory loss and other symptoms of cognitive decline.1 Although it was discovered over a century ago, Alzheimer’s disease only gained traction in the biomedical research field starting in the late 70s, when it was recognized as the most common form of dementia and began garnering awareness and momentum in academia.2 Over the next two decades, biomarkers such as beta-amyloid, p-tau, t-tau, and the risk factor gene APOE-e4 were progressively discovered.2 Despite the many strides in research and the development and approval of a few drugs targeting Alzheimer’s memory and cognitive symptoms, the first therapy to address the underlying biology of AD—Aducanumab (Aduhelm®) —was only approved in 2021.2 As of November 2024, this drug was discontinued, but in 2023, Lecanemab (Leqembi®) received traditional approval from the FDA as a treatment for early Alzheimer's, also addressing underlying biology and changing the course of the disease in its early stages.2 Lecanemab works to remove beta-amyloid proteins from the brain, and—according to Dr. Ferrell—after tackling the first-discovered and most understood biomarker, the Alzheimer’s drug development industry is now focusing on increasing the effectiveness of beta-amyloid treatments, addressing other biomarkers, and attempting to find additional solutions by further researching and understanding the biology of the disease.
Throughout her 30 years of experience at Eli Lilly and Company, Dr. Phyllis Ferrell worked in not only sales, marketing, business development, and strategy, but also late-stage medical and diagnostic development. Since taking an early retirement, she has leveraged this diverse background to consult for organizations ranging from smaller nonprofits to larger biotechnology companies. This consulting work focuses on medical affairs, corporate affairs, and external engagement, assisting clients in achieving their drug development goals in brain health, Alzheimer’s disease, and longevity. Her work largely revolves around the delivery stage of development, particularly health system engagement and preparedness. In addition to her consulting roles, Dr. Ferrell is an engaged investor in the industry. She evaluates companies and their innovations from early research and developmental stages to market transitions and patient engagement.
As Dr. Ferrell walked us through her process for evaluating companies and innovations, several parallels emerged with the challenges emerging in the Alzheimer’s disease sector. For instance, she mentioned first identifying whether the science behind an idea was legitimate, valuable, and based on solid fundamentals, therefore leading to a “high probability of technical success.” In the Alzheimer’s sector, the majority of the work being done is in research—whether in academia or industry—to better understand the underlying disease biology. In Dr. Ferrell’s words, Alzheimer’s is a “nascent area in clinical practice,” an ideareinforced by the fact that we are seeing the first drugs to launch in the sector in 35 years.
Once the underlying biology of the disease is understood, then a druggable target must be found, after which a drug can finally be designed to hit the said target. “There is a process by which targets move,” Ferrell says, but as research progresses to discover new biomarkers and potential routes to regulate them, the industry grows restless. She mentions one particular complaint of only studying amyloid to which she responds: “That’s because that was the first thing we really understood from an underlying biology [perspective], and it was the first druggable target, so of course it’s going to come out first.” Although the idea of vaccines or gene editing in Alzheimer’s disease is exciting, there is simply not enough concrete knowledge on the biology to do it safely. Dr. Ferrell draws a comparison to the COVID-19 vaccine, “People will say, ‘We were able to do a COVID vaccine so fast. Why can’t we do an Alzheimer’s disease vaccine?’ But in the case of COVID, you can see SARS-CoV-2! You can see it, so you can target it with a vaccine that can bind to it, but we don’t know enough about the underlying biology of Alzheimer’s to do the same.” And for vaccines and gene editing, a permanent change is being made to an individual’s biology, making it crucial to understand what exactly a particular genetic change or vaccine delivery does to the body, which is not a level of understanding that the Alzheimer’s sector has yet achieved. Ferrell mentions how the industry tested gamma secretase inhibitors and beta secretase inhibitors thinking they understood what the full impacts would be, only to find significant side effects. Thus, jumping into genetic testing and drug development without developing a comprehensive understanding of Alzheimer’s first could be a fatal mistake.
From the scientific perspective, Dr. Ferrell expects drug development to follow the same trends as research, where current amyloid treatments will be followed by tau pathology treatments, then possibly neuroinflammation. In terms of genetic therapies, she mentions that 2% of Alzheimer’s disease comes from rare genetic (presenilin) mutations, which will probably be targeted first. She notes, in particular, the challenge of Alzheimer’s therapies counting on early and accurate diagnoses, which rarely happens in reality.
Once the science behind an innovation is sound, Dr. Ferrell believes the next question is whether or not the market strategy is well thought-out. Through the lens of her consulting and investing work, several challenges in the current Alzheimer’s disease industry are illuminated both in the context of individual organizations and the larger healthcare delivery system. Dr. Ferrell refers to The Innovator’s Dilemma by Clayton Christensen, pointing out three steps in delivering a drug innovation to a patient: zero to one, in which a drug passes the regulatory process and reaches one patient; one to many, in which a drug is commercially launched; and many to all, in which underserved populations such as low and middle income countries or areas in the U.S. with low social determinants of health may be able to access the drug. “If you can’t get innovation paid for, that innovation will never get to patients,” Ferrell states, and although this seems obvious, she explains how it underscores an important struggle in Alzheimer’s disease. Very little healthcare in the U.S. is truly out-of-pocket, leading the general population to view healthcare as an entitlement. As such, it is extremely difficult to request people to pay out-of-pocket for treatments and care that they feel should be covered by insurance or the government. In the case of Alzheimer’s disease, Ferrell believes the sector exists in a kind of single-payer system unlike the rest of US healthcare as patients are largely likely to be above age 65 and thus Medicare beneficiaries.
Zooming back in on individual organizations, Ferrell describes the struggle of financing innovations. Often, she states, organizations will try to be all things to all people, which only sets them up for failure. She mentions that in the process of making good strategic choices, it is imperative for organizations and companies to think about what they are not going to do as much as what they are going to do. Once these priorities are designated, organizations must then concern themselves with finding mission-aligned funders and venture capitalists that support them and make sure they make good decisions that “support their future goals rather than chasing a fast buck.” Although organizations may achieve these initial objectives, the structure of the US healthcare system nonetheless makes the last step of delivery difficult. The US consists of vertically integrated health systems, throughout which algorithms for delivery are not prescribed by the government. This leads to a high variability in the uptake of particular treatments into the system. Dr. Ferrell says, “[Uptake] could happen faster in the U.S. in some systems, but it will definitely happen slower in all systems.” To draw a comparison, she brings up theUnited Kingdom. In the UK, the National Health Service (NHS) effectively makes one, largely-unilateral decision that everyone in the system must then implement. This creates a slower process in the first step where the decision is made, but after that, implementation and uptake are sped up. In the US, however, there is no unilateral decision to be made, and one system may choose to adopt a new technology while another may not, meaning access to particular treatments and care end up depending on an individual’s zip code rather than what is approved by the FDA.
Even approval from the FDA has become a point of concern recently. Right now, the biotech market is incredibly anxious about the Trump administration coming in, specifically the appointment of Robert Kennedy Jr. to lead the Department of Health and Human Services. In pharmaceuticals, diagnostics, and research, organizations want to go to a regulator, describe their plan and the study they will run, and expect a regulator to grant approval if they can run the study and prove that their innovation works. However, Ferrell says, "These studies could be 5 years [long] and [cost] 3 billion dollars, especially in Alzheimer’s, and you don’t want to get halfway through the study and have the regulator change their opinion when they’ve already made a commitment.” While there is a definite desire for progress, organizations also want certainty before embarking on these expensive and extensive processes, and that level of certainty from regulators may become more difficult to acquire under the Trump administration. Even now, the Alzheimer’s industry struggles with this issue. Eisai, for instance, pitched Leqembi® to the European Medicines Agency (EMA) and acquired alignment with regulators on the study they were going to run as well as the endpoints they intended to meet. They then ran the study and achieved the intended outcomes, but the first opinion of the Committee for Medicinal Products for Human Use (CHMP) was to not approve the drug, changing their minds after looking at risk-benefit analyses. They eventually reversed their position, and the EMA approved Leqembi, but the situation exemplifies the daunting concern of regulatory certainty. In Dr. Ferrell’s words, “You will shut down innovation if you don’t have some sort of regulatory certainty before someone begins investing.” Scientific progress should be encouraged, and if knowledge is acquired in science, innovations should evolve. That being said, Dr. Ferrell also states that “companies cannot be expected to make the kinds of investments they need to make in the last phase of development without some sort of certainty in regulatory guidance.”
Despite some of the obstacles facing the Alzheimer’s disease sector, there is hope. The sector is tight-knit, meaning new findings are shared quickly and organizations are eager to support each other. Dr. Ferrell’s work exposes her to many different types of organizations, and she hopes that these organizations will continue to work together on projects. Looking to the future, Dr. Ferrell expresses hope for collaboration. She emphasizes that industry, academia, and non-profit organizations each have a role to play in achieving progress, and, “If you think you can do it alone, you’re going to fail.” Additionally, in recent years, Alzheimer’s disease has received more attention and awareness than ever before, leading to more conversations with doctors and families that create a positive feedback loop for the research and development sector. These conversations not only allow individuals to work to prevent or prepare for Alzheimer’s disease, but they also draw in new capital for the sector, creating the necessary funding for new, cutting-edge treatments.

Researcher: Aditi Dey
Editor: Tiago Johnson
Illustrator: Yuanhui Li

1 Alzheimer's Association. 2019. “Milestones.” Alzheimer’s Disease and Dementia. 2019. https://www.alz.org/alzheimers-dementia/research_progress/milestones.Yang, Hyun Duk, Do

2 Han Kim, Sang Bong Lee, and Linn Derg Young. 2016. “History of Alzheimer’s Disease.” Dementia and Neurocognitive Disorders 15 (4): 115.