How the First Alzheimer's Drugs Are Just the Start

Sir John Hardy, a neuroscientist at University College London, helped establish in the 1990s that a protein called amyloid plays a central role in Alzheimer's disease. Speaking at a WIRED Health event, he made a clear point: the two new FDA-approved Alzheimer's drugs hitting the market in 2024 are only the beginning of effective treatment — not the end goal.

Those drugs are lecanemab (approved in January) and donanemab, branded as Kisunla (approved in July). They represent the first therapies that can actually remove amyloid deposits from the brain, after decades of drug candidates that failed. Hardy's research directly paved the way for both.

Yet the clinical evidence shows both benefits and real limits. Lecanemab slows cognitive decline in early-stage Alzheimer's patients but cannot stop the disease entirely. Donanemab reduced memory and thinking decline by 29 percent compared to a placebo group — meaningful, but still far from halting progression. Patients on both drugs continued to decline.

The Real Bottleneck: Diagnosis and Access

Hardy stressed at the event that better drugs alone are not enough. Healthcare systems need to invest in diagnostic infrastructure and care delivery systems. Right now, many Alzheimer's patients are misdiagnosed, and diagnostic accuracy remains a significant problem.

This diagnostic bottleneck creates a larger problem: clinical trials are understaffed. Only about 12,000 Alzheimer's patients join trials each year, but the 182 trials currently underway need more than 50,000 participants. Polling shows most American adults say they would be interested in joining an Alzheimer's trial — yet the infrastructure to recruit and manage them does not exist.

One consequence is that promising treatments move slower through the pipeline. For example, ALZ-801 could be the first oral Alzheimer's drug (the current therapies require IV infusions), with an FDA application expected in 2024. But trial capacity constraints delay the development timeline.

Safety Trade-Offs Limit Who Can Be Treated

Both amyloid-clearing drugs come with significant safety concerns. Donanemab can cause brain swelling, fluid buildup, and microhemorrhages — side effects called amyloid-related imaging abnormalities, or ARIA. These require regular MRI scans throughout treatment to monitor, adding cost and complexity to patient care.

Because of these risks, both drugs are currently approved only for patients with mild cognitive impairment or early-stage dementia. Advanced Alzheimer's patients who might benefit from clearing amyloid cannot safely receive these treatments, or the monitoring demands make it impractical.

The regulatory path for both drugs moved unusually fast by historical standards. The FDA reviewed donanemab data in June 2024 and approved it within weeks. This speed reflects how desperately the field needed these drugs, and how strong the efficacy data looked on paper. But that speed also underscores why close watching for side effects after approval — the kind of monitoring that happens once millions of patients use a drug — will be crucial.

A Bigger Pipeline Is Already Moving

The Alzheimer's research landscape has shifted dramatically. In 2024, 171 ongoing studies are testing 134 distinct drug candidates — the largest coordinated research effort in the field's history. This reflects both new confidence in tractable drug targets and significant venture capital investment in neurodegenerative disease research over the past five years.

Many of these newer candidates target mechanisms beyond amyloid. Some focus on tau, another protein that accumulates in Alzheimer's brains. Others target neuroinflammation — the brain's inflammatory response — or try to preserve synaptic connections between neurons. The thinking is that amyloid removal, while necessary, may not be enough on its own for most patients.

Global expansion is already underway. Eisai's lecanemab won approval in China in January 2024, and Eli Lilly's donanemab followed in December. These international approvals will generate real-world evidence about how these drugs work across different patient populations.

A Historical Parallel

This moment in Alzheimer's research resembles the mid-1990s when the first HIV protease inhibitors arrived. These drugs showed they could suppress the virus, but researchers soon discovered that one drug was not enough. Combination therapy — attacking the virus from multiple angles — proved essential for sustained control. The Alzheimer's field is likely heading in a similar direction: multiple drugs targeting different disease mechanisms, used together rather than alone.

Hardy's career illustrates how long this journey takes. In the late 1990s, his work identified mutations in the amyloid precursor protein gene at UCL — discoveries that laid the foundation for today's amyloid-clearing antibodies. But moving from "we found the target" to "here is an approved drug" required three decades and advances in protein engineering, biomarker development, and clinical trial design.

What This Actually Requires

Deploying these new drugs across healthcare systems will demand more than just buying pills or infusions. Hospitals and clinics need specialized imaging equipment, enough neurologists to prescribe and monitor treatment, and infusion centers to administer drugs. Many healthcare networks lack these resources, and access will be uneven.

Hardy's broader argument is that solving the dementia crisis will take coordination across many levels: better diagnostic standards, improved care coordination between hospitals and primary care, and sustained research funding. The new drugs prove that disease modification is possible in Alzheimer's — that we can actually intervene in the disease process, not just manage symptoms. But the gap between a working drug and a working healthcare system remains large.

Looking ahead, the field is moving toward combination therapies — pairing one drug with another to target different disease mechanisms simultaneously. Karuna Therapeutics, for example, recently succeeded in pairing an Eli Lilly Alzheimer's candidate with a separate mechanism for treating schizophrenia. This signals that the next frontier is multi-target approaches addressing the full spectrum of neurological damage in dementia.

Hardy's recognition on Esquire's 2025 Better Men List reflects his role in the scientific breakthroughs that made this moment possible. But his inclusion also serves as a reminder of the distance between an initial discovery and a comprehensive solution. The path from genetic discovery to clinical application continues, with the next phase focused on getting these drugs to patients who need them, optimizing how they work together, and ultimately developing treatments that can stop disease progression rather than just slow it down.