WASHINGTON, July 14 — The story of aducanumab, the first Alzheimer’s treatment to target the underlying disease process rather than just symptoms, remains one of the most contentious chapters in modern drug regulation. Approved by the U.S. Food and Drug Administration in June 2021 under its accelerated approval pathway, the drug — developed by Biogen and sold under the brand name Aduhelm — was intended for patients with early Alzheimer’s disease. The FDA’s decision was based on the drug’s ability to reduce amyloid plaques in the brain, a surrogate endpoint.
The agency acknowledged that direct evidence of cognitive improvement was not yet established. This reliance on a biomarker rather than clinical benefit sparked immediate controversy.
Three members of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee resigned in protest. ## The Trials That Stopped and Started The clinical development of aducanumab was anything but straightforward. Biogen halted two Phase 3 trials, named ENGAGE and EMERGE, in March 2019 after a routine futility analysis suggested the drug was unlikely to show benefit. But later, a reanalysis of the data indicated that patients in the high-dose group of one trial — EMERGE — did show some benefit.
This reversal led Biogen to pursue FDA approval. The company initially set the price of Aduhelm at $56,000 per year.
After widespread criticism from insurers, patient advocates, and policymakers, Biogen cut that price in half to $28,000 per year. The Centers for Medicare & Medicaid Services, or CMS, issued a national coverage determination in April 2022 that sharply limited access. Under that policy, Medicare would only cover aducanumab and other anti-amyloid antibodies for patients enrolled in randomized controlled trials.
This effectively restricted the drug to a small number of research participants, not the broader population of Alzheimer’s patients. ## A Shifting Treatment Landscape For decades, Alzheimer’s treatment relied on symptomatic therapies. Cholinesterase inhibitors such as donepezil, rivastigmine, and galantamine were approved in the 1990s. These drugs can temporarily improve or stabilize cognitive symptoms, but they do not alter the course of the disease.
Aducanumab represented a different approach — a disease-modifying therapy aimed at removing amyloid plaques, one of the hallmark pathologies of Alzheimer’s. The encouraging part for researchers and patients is that this class of drugs has continued to evolve.
In January 2023, the FDA granted accelerated approval to lecanemab, developed by Eisai. Unlike aducanumab, lecanemab had stronger Phase 3 data that showed a statistically significant cognitive benefit. Eisai set the list price for lecanemab at $26,500 per year, lower than even the reduced price of Aduhelm.
The CMS coverage decision for lecanemab is expected to be similar to that for aducanumab, requiring registry participation. This means that while the drug is approved, patients will likely need to enroll in a clinical registry for Medicare to cover the treatment. ## What This Means for Patients For patients and families navigating Alzheimer’s disease, these developments offer cautious hope.
The shift from purely symptomatic treatments to disease-modifying approaches is a meaningful step forward. Early findings suggest that targeting amyloid plaques may slow cognitive decline in some patients. But the path to approval has been messy, and the access restrictions imposed by CMS mean that many patients who might benefit from these drugs cannot easily get them.
Patients should talk to their doctors about whether they might be candidates for these therapies, and whether participation in a clinical trial or registry is an option. The story of aducanumab is not just about one drug. It is about how the FDA, CMS, drugmakers, and the medical community are learning to evaluate and regulate a new class of Alzheimer’s treatments.
The science is still young, and the debate over surrogate endpoints versus clinical outcomes is far from settled. What is clear is that Alzheimer’s treatment is no longer limited to managing symptoms.
Disease-modifying therapies have arrived, and the coming years will determine how widely they reach the patients who need them. Consult your doctor for medical advice.
