Aducanumab, sold under the brand name Aduhelm, is not an effective treatment for Alzheimer’s disease by most meaningful clinical standards, and it carries significant safety risks. The drug was controversially approved by the FDA in June 2021 based not on demonstrated cognitive benefit but on its ability to reduce amyloid plaques in the brain — an intermediate biomarker whose link to patient outcomes remains disputed. By January 2024, the drug’s manufacturer, Biogen, had pulled it from the market entirely, discontinuing development and terminating its follow-up clinical trial.
The story of aducanumab is a cautionary tale about the pressures surrounding Alzheimer’s drug approval, the limits of surrogate endpoints, and the real harm that can come from treatments given too little scrutiny. This article covers what the clinical trials actually showed, why the FDA’s approval was so contested, what risks patients faced, and where the field of Alzheimer’s treatment stands now that aducanumab is no longer available. For families and caregivers trying to understand the evolving landscape of dementia therapies, the aducanumab episode offers important context for evaluating the next generation of treatments.
Table of Contents
- Was Aducanumab Actually Effective for Alzheimer’s Disease?
- How Did the FDA Approve Aducanumab Despite Contradictory Trial Results?
- What Are the Safety Risks of Aducanumab?
- Why Did Biogen Discontinue Aducanumab?
- What Did the Expert Community Say and Why Does It Matter?
- How Does Aducanumab Compare to Newer Alzheimer’s Treatments?
- What the Aducanumab Controversy Means for the Future of Alzheimer’s Research
- Conclusion
- Frequently Asked Questions
Was Aducanumab Actually Effective for Alzheimer’s Disease?
The clinical evidence for aducanumab’s effectiveness was, at best, deeply mixed. Two identical Phase 3 trials — called EMERGE and ENGAGE — enrolled 1,812 patients aged 50 to 85 with early-stage Alzheimer’s disease. EMERGE appeared to show a roughly 22% slowing of cognitive decline. ENGAGE, run under the exact same protocol, showed almost no effect — only around 2%. When two near-identical trials produce such different results, it raises serious questions about whether either result reflects a real drug effect or statistical noise.
The scale used to measure cognitive decline in both trials was the CDR-SB, a standard clinical tool for Alzheimer’s assessment. The observed improvement in EMERGE amounted to approximately one point on that scale. Researchers generally consider a minimum of three points necessary to represent a clinically meaningful change — something a patient or caregiver would actually notice in daily life. In other words, even the best-case trial result fell well short of what would constitute a detectable benefit for real patients. The drug did reliably reduce amyloid-beta plaques in the brain — by 59 to 71 percent at 18 months — but amyloid reduction did not translate into consistent cognitive improvement across both trials, calling into question the amyloid hypothesis itself as a reliable treatment target.
How Did the FDA Approve Aducanumab Despite Contradictory Trial Results?
The FDA approved aducanumab in June 2021 under its accelerated approval pathway, which allows drugs to receive approval based on a surrogate endpoint — in this case, amyloid plaque reduction — rather than direct proof of clinical benefit. The agency argued that reducing amyloid plaques was reasonably likely to predict cognitive benefit, even though the trials themselves had not demonstrated that connection clearly. This decision was remarkable for several reasons, not least because the FDA’s own independent advisory committee had voted nearly unanimously against approval, finding the evidence insufficient. The approval set off a wave of criticism from neurologists, ethicists, and health policy researchers.
The New England Journal of Medicine published multiple commentaries describing the decision as a problematic precedent, warning that approving drugs based on biomarker surrogates without demonstrated patient benefit could open the door to a range of poorly supported therapies in the future. The American Academy of Family Physicians went further, issuing explicit guidance that physicians should not prescribe aducanumab. When the medical establishment issues that kind of statement about an FDA-approved drug, the gulf between regulatory decision-making and clinical judgment becomes impossible to ignore. Medicare, for its part, restricted coverage for aducanumab to patients enrolled in approved clinical trials — an unusual step that effectively blocked most patients from accessing the drug even if their doctors wanted to prescribe it. The result was that, despite FDA approval, aducanumab saw almost no real-world use.
What Are the Safety Risks of Aducanumab?
The safety profile of aducanumab was a serious concern throughout its development. The most significant risks involved a class of side effects called ARIA — amyloid-related imaging abnormalities. These appear on MRI scans as either brain swelling (ARIA-E, for edema) or small bleeds in the brain (ARIA-H, for microhemorrhage). In the clinical trials, ARIA-E occurred in approximately 35% of treated patients, and ARIA-H occurred in approximately 21%. Combined, roughly 41% of patients experienced the most serious ARIA events attributable to the drug. To put that in context: more than one in three patients on aducanumab developed some degree of brain swelling, and more than one in five developed small brain bleeds.
Most ARIA events were described as asymptomatic or mild, but some required discontinuation of treatment, and all required regular MRI monitoring to detect. For elderly patients with Alzheimer’s disease — many of whom may already have cerebrovascular vulnerabilities — this level of neurological risk is not trivial. The monitoring burden alone added cost and complexity to a treatment that had not clearly demonstrated it was helping patients think or function better. There were also practical consequences. Patients on blood thinners or with certain pre-existing vascular conditions were at elevated risk, limiting who could even safely attempt the therapy. The combination of uncertain benefit and confirmed, frequent harm placed aducanumab in an unusual position: a drug where the risk-benefit calculus was difficult to justify for the vast majority of candidates.
Why Did Biogen Discontinue Aducanumab?
In January 2024, Biogen announced it was discontinuing the development and commercialization of aducanumab entirely, including the termination of the ENVISION follow-up trial that had been designed to provide additional evidence of effectiveness. The company cited a “reprioritization” of its Alzheimer’s portfolio, but the commercial reality was clear: the drug had failed to gain traction with patients, physicians, or insurers. Medicare’s restrictive coverage policy, physician resistance, and the logistical burden of required MRI monitoring had combined to make aducanumab commercially nonviable. The withdrawal marked the effective end of a years-long controversy. For the families of the 1,812 patients who participated in the original trials — some of whom had held genuine hope that this drug might slow their loved one’s decline — the outcome was a painful disappointment.
One way to understand the stakes: a patient with early Alzheimer’s enrolled in the EMERGE trial received a drug that produced, in the best-case reading, a one-point improvement on a cognitive scale requiring three points for clinical significance, while facing more than a one-in-three chance of brain swelling. That tradeoff, in retrospect, never looked favorable. The withdrawal also cleared the field for competing anti-amyloid antibodies that had stronger evidence behind them. Lecanemab, sold as Leqembi, and donanemab, sold as Kisunla, have since shown more consistent results across trials and have become the primary focus of anti-amyloid treatment discussions. Neither is without risk — ARIA is a class effect that appears across this drug category — but both carry a more defensible evidence base than aducanumab ever did.
What Did the Expert Community Say and Why Does It Matter?
The near-universal expert pushback against aducanumab’s approval was unusual in its directness. The FDA’s advisory committee, composed of independent scientists, voted 10 to 0 against approval, with one abstention, before the FDA overruled them. The NEJM published commentary from prominent neurologists and bioethicists describing the approval as a failure of the regulatory process that could harm public trust in both the FDA and the broader Alzheimer’s research enterprise. The AAFP’s explicit guidance against prescribing the drug — published in the journal American Family Physician — was the kind of unambiguous clinical guidance that rarely accompanies an approved therapy. One concern raised repeatedly was that the approval might discourage patients from enrolling in clinical trials for genuinely promising treatments.
If a drug with weak evidence is available outside a trial, patients may choose it over structured research participation, slowing the generation of good data for better therapies. The aducanumab situation also prompted broader discussions about when surrogate endpoints are — and are not — acceptable as the basis for approval in conditions like Alzheimer’s, where clinical outcomes are slow to measure and patients are desperate for options. Those conversations are ongoing and have directly shaped how newer drugs in this class are being evaluated. A 2025 systematic review and network meta-analysis published in JMIR confirmed what the trial data had suggested: aducanumab showed small effect sizes compared to other anti-amyloid antibodies. That conclusion, emerging years after approval, underscores how the accelerated pathway can result in drugs reaching market before the full picture of their limitations is understood.
How Does Aducanumab Compare to Newer Alzheimer’s Treatments?
The anti-amyloid antibody class that aducanumab belonged to has not been abandoned — it has been refined. Lecanemab and donanemab, the two successors that have attracted the most clinical attention, both received FDA approval based on data showing statistically significant slowing of decline on multiple clinical endpoints, not just biomarker changes. That does not mean they are without controversy or risk. Both carry ARIA risks similar to aducanumab, and questions remain about the real-world magnitude of their cognitive benefits.
But the evidence supporting them is more consistent across trials than what aducanumab offered, and the medical community’s reception has been more measured rather than openly oppositional. For caregivers trying to evaluate these newer options, the aducanumab story provides a useful framework: ask what the drug actually did for patients’ thinking and functioning, not just what it did to a biomarker. Ask about the frequency and severity of side effects. Ask whether the FDA’s advisory committee supported the approval. These are not hostile questions — they are the right ones.
What the Aducanumab Controversy Means for the Future of Alzheimer’s Research
The aducanumab episode will likely influence Alzheimer’s drug development and regulation for years. It prompted the FDA to clarify its expectations around accelerated approvals and the need for confirmatory trials. It intensified scrutiny of the amyloid hypothesis, which holds that reducing amyloid plaques in the brain is the key to slowing Alzheimer’s.
While that hypothesis has not been abandoned — the modest successes of lecanemab and donanemab suggest it still has validity — the field is increasingly recognizing that amyloid reduction alone may not be sufficient, and that targeting other pathways, including tau protein and neuroinflammation, may be necessary for more meaningful results. For patients and families navigating early Alzheimer’s diagnoses today, the takeaway is that this field is moving, imperfectly but genuinely forward. Aducanumab’s failure, and the controversy it generated, helped raise the evidentiary bar for what comes next. That is not a small thing.
Conclusion
Aducanumab was approved by the FDA in 2021 under conditions that most of the medical community found inadequate, and it was withdrawn from the market by its manufacturer in early 2024 before it reached meaningful use. The drug’s clinical trials produced contradictory results, and the best outcome observed — a one-point change on a scale where three points is the minimum clinically meaningful threshold — fell well short of what patients and caregivers would need to see to justify a treatment that caused brain swelling in more than a third of recipients. The expert consensus, from the FDA’s own advisory committee to the AAFP to the pages of the New England Journal of Medicine, was that the drug should not have been approved.
For anyone trying to understand the current state of Alzheimer’s treatment, the aducanumab story is essential context. It illustrates how much pressure surrounds drug approval in a disease with no good options, how surrogate endpoints can create the appearance of progress without delivering it, and why skepticism of new approvals — even welcome ones — is a form of patient protection, not cynicism. The treatments that have followed, lecanemab and donanemab, carry their own limitations and risks, but they represent a more credible step forward. Families making decisions about Alzheimer’s care should seek current guidance from neurologists familiar with the evolving evidence, and should approach any new treatment claim with the same careful questions this episode teaches us to ask.
Frequently Asked Questions
Is aducanumab still available for Alzheimer’s patients?
No. Biogen discontinued development and commercialization of aducanumab in January 2024, effectively withdrawing it from the market. It is no longer an available treatment option.
Why did the FDA approve aducanumab if the trials were inconclusive?
The FDA used its accelerated approval pathway, which allows approval based on a surrogate endpoint — in this case, amyloid plaque reduction — rather than demonstrated clinical benefit. The agency determined that amyloid reduction was reasonably likely to predict patient benefit, despite the inconsistent trial results. Its own advisory committee disagreed with that decision.
What is ARIA and how serious is it?
ARIA stands for amyloid-related imaging abnormalities. It refers to brain swelling (ARIA-E) or small brain bleeds (ARIA-H) that appear on MRI scans. In aducanumab trials, ARIA-E occurred in about 35% of patients and ARIA-H in about 21%. Most cases were mild or asymptomatic, but the frequency required regular MRI monitoring and led to treatment discontinuation in some patients.
What treatments have replaced aducanumab?
The two leading anti-amyloid antibodies now are lecanemab (Leqembi) and donanemab (Kisunla). Both have shown more consistent clinical evidence than aducanumab, though both also carry ARIA risks and remain subjects of ongoing evaluation.
Did any patients benefit from aducanumab?
In the EMERGE trial, a 22% slowing of cognitive decline was observed. However, the actual measured improvement was approximately one point on the CDR-SB scale, below the three-point threshold considered clinically meaningful. The identical ENGAGE trial showed only a 2% effect, making it difficult to conclude that the EMERGE result was a reliable drug effect.
Why did Medicare restrict coverage of aducanumab?
Medicare (CMS) limited coverage to patients enrolled in approved clinical trials because the evidence of clinical benefit was considered insufficient to justify broader reimbursement. This effectively prevented most patients from accessing the drug even after FDA approval.
