When the FDA granted accelerated approval to Leqembi and Kisunla in 2023, the headlines sounded like a turning point in the century-long fight against Alzheimer’s disease. Here, at last, were drugs that didn’t just mask symptoms but appeared to slow the relentless erosion of memory and self. Patients and families dared to hope. Investors poured billions into biotech stocks. The promise was simple and seductive: science had finally cracked the code.
Two years later, the reality is far more nuanced—and considerably more troubling. A recent analysis published in JAMA Neurology has reignited debate over whether these much-touted therapies deliver meaningful clinical benefit, or if they represent an expensive detour in a field desperate for answers. The study found that while both drugs successfully reduce amyloid-beta plaques in the brain—their primary mechanistic target—the translation into tangible improvements in cognition or daily functioning remains marginal at best. For many patients, the difference between treatment and placebo is barely perceptible outside of highly controlled clinical settings.
This gap between biological effect and clinical relevance has exposed a deeper fracture in how we evaluate progress against neurodegenerative disease. Regulatory pathways designed for acute conditions like cancer or infectious diseases are being applied to a slow-moving, multifaceted syndrome where surrogate biomarkers may not reliably predict patient-centered outcomes. As one neurologist put it bluntly during a recent FDA advisory committee meeting: “We are mistaking the map for the territory.”
“The amyloid hypothesis has guided Alzheimer’s research for decades, but we’ve learned that clearing plaques doesn’t automatically restore function. We require to measure what matters to patients—remembering their grandchildren’s names, managing their finances, dressing themselves—not just what shows up on a PET scan.”
The financial implications are staggering. Leqembi carries an annual list price of $26,500. Kisunla, approved more recently, is priced at $32,000 per year. When factoring in required biweekly infusions, brain monitoring via MRI, and management of side effects like cerebral edema and microhemorrhages—which occur in up to 35% of patients—the true cost to the healthcare system could exceed $50,000 annually per patient. With an estimated 6.7 million Americans aged 65 and older living with Alzheimer’s dementia, even modest adoption rates would strain Medicare’s already strained budget.
Critics argue that these expenditures divert resources from potentially more impactful interventions. “We’re spending billions on drugs that offer, at best, a few extra months of mild cognitive stability,” says Dr. Jason Karlawish, professor of medicine and medical ethics at the University of Pennsylvania. “Meanwhile, we underfund care coordination, caregiver support, and non-pharmacological approaches like cognitive stimulation and physical activity—interventions with proven benefits and far lower costs.”
“If we truly want to alter the trajectory of this disease, we must invest in prevention and lifelong brain health—not just chase silver bullets in late-stage trials.”
The international response has been fragmented. While the FDA moved swiftly under its accelerated approval pathway, the European Medicines Agency initially declined to authorize Leqembi, citing insufficient evidence of clinical benefit relative to risk. After a re-examination, it granted conditional approval in early 2025—but with strict requirements for real-world evidence generation and restricted use to early-stage patients enrolled in registries. The UK’s National Institute for Health and Care Excellence (NICE) has gone further, declining to recommend either drug for routine use within the NHS, stating that the “small, uncertain benefits do not justify the significant costs and risks.”
This divergence highlights a growing transatlantic split in regulatory philosophy. American agencies often prioritize access to innovative therapies, even amid uncertainty, while European counterparts emphasize cost-effectiveness and robust proof of patient benefit. The tension reflects not just differing healthcare systems, but contrasting values about what constitutes meaningful progress in the face of scientific ambiguity.
Beyond policy, there’s a human dimension too often lost in the debate. For families grappling with an Alzheimer’s diagnosis, the promise of any treatment—no matter how modest—can perceive like a lifeline. Yet the infusion clinics where these drugs are administered have begun to resemble assembly lines, with patients spending hours in recliners while nurses monitor for adverse reactions. Some describe the experience as clinically impersonal, even alienating—a stark contrast to the dignified, relationship-centered care many had hoped for.
Looking ahead, the field is at a crossroads. Researchers are increasingly exploring combination therapies that target multiple pathways—tau tangles, neuroinflammation, metabolic dysfunction—alongside amyloid. Blood-based biomarkers are improving, potentially enabling earlier, less invasive diagnosis. And prevention trials focusing on lifestyle factors like diet, exercise, and sleep are showing encouraging signals in high-risk populations.
But none of this will matter if we continue to conflate biochemical activity with clinical success. The drugs themselves are not failures; they are proof of concept. What remains unproven is whether targeting amyloid alone—especially in symptomatic disease—can alter the course of a condition shaped by decades of silent neurodegeneration.
As we navigate this uncertain terrain, perhaps the most important question isn’t whether these drugs work, but what we’re willing to accept as progress. Are we satisfied with slowing the decline by a fraction, or should we demand more? And in our pursuit of pharmaceutical solutions, are we neglecting the simpler, older truths—that connection, routine, and dignity matter deeply, even when memory fades?
What do you believe—should we redefine what counts as a meaningful breakthrough in Alzheimer’s care?
