For decades, every promising Alzheimer’s drug failed. Every single one. Treatments could mask symptoms by managing agitation or smoothing sleep cycles, but nothing touched the disease itself. That changed in July 2024, when the FDA approved Eli Lilly’s donanemab (brand name Kisunla), making it only the second therapy ever cleared to modify the actual course of Alzheimer’s disease [Clinicaltrialsarena]. The European Commission granted marketing authorization in September 2025, and long-term extension data continues to emerge [Clinicaltrialsarena]. The evidence base around this drug is maturing rapidly. What we’re learning reshapes how families, clinicians, and researchers think about a disease affecting over 55 million people worldwide.
This isn’t a cure. That distinction matters. But the shift from “manage symptoms” to “slow biological progression” represents a fundamentally different conversation.
What Donanemab Actually Does
Most earlier Alzheimer’s medications like donepezil or memantine work downstream, boosting neurotransmitter levels to temporarily prop up cognition.
Photo by Donanemab operates at the source. It’s a monoclonal antibody that binds specifically to pyroglutamate-modified amyloid beta, a particularly stubborn form of the protein plaques that accumulate in Alzheimer’s-affected brains [eLife Sciences].
Once bound, the drug flags these plaques for removal by the immune system. The results from the TRAILBLAZER-ALZ 2 trial were striking:
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An average 84% reduction in amyloid plaques at 18 months [Clinicaltrialsarena]
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Cognitive and functional decline slowed by up to 35% compared to placebo [Clinicaltrialsarena]
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Risk of progressing to the next clinical stage reduced by up to 39% [Clinicaltrialsarena]
Donanemab is designed as a finite treatment course. Patients receive monthly IV infusions, and once brain scans confirm sufficient plaque clearance (typically within 12 to 18 months), treatment stops. This contrasts with lecanemab (Leqembi), the other approved disease-modifying therapy, which requires ongoing biweekly infusions.
A subgroup of treated patients in the TRAILBLAZER-ALZ 2 long-term extension maintained cognitive benefit for two years, suggesting the effects may persist beyond the active treatment window [Neurology Live]. That’s meaningful for families weighing options.
Who May Benefit Most
Donanemab doesn’t work for everyone.
Photo by Acknowledging that variation honestly matters more than overpromising.
The strongest evidence supports use in people with mild cognitive impairment or early-stage Alzheimer’s dementia who have confirmed amyloid plaques. Verification comes through PET imaging or cerebrospinal fluid testing. In the TRAILBLAZER-ALZ 2 trial, patients with low-to-intermediate levels of tau pathology (another hallmark Alzheimer’s protein) showed substantially better outcomes than those with advanced tau burden [Clinicaltrialsarena].
This creates an important implication: early detection dramatically shapes eligibility and potential benefit. By the time Alzheimer’s reaches moderate or advanced stages, neuronal damage has progressed beyond what plaque removal alone can meaningfully address.
Safety considerations exist. The primary risk is ARIA (amyloid-related imaging abnormalities), which includes brain swelling or microbleeds detectable on MRI. Eli Lilly’s TRAILBLAZER-ALZ 6 trial demonstrated that a modified dosing schedule reduced ARIA-E incidence by 41% compared to the original regimen [Clinicaltrialsarena]. Still, regular MRI monitoring remains necessary during treatment, and individuals carrying two copies of the APOE4 gene face elevated ARIA risk.
“The modified titration schedule reduced ARIA-E incidence by 41% at week 24: 14% versus 24% compared to the original regimen.” (TRAILBLAZER-ALZ 6 data) [Clinicaltrialsarena]
A Shifting Treatment Landscape
Donanemab’s approval doesn’t exist in isolation. It accelerates a broader transformation in how the field approaches Alzheimer’s.
The amyloid hypothesis (the idea that amyloid plaque accumulation drives the disease) spent years under fierce debate. Aducanumab’s controversial 2021 approval did little to settle the argument. Donanemab’s cleaner trial data and more convincing clinical outcomes have strengthened the case, though researchers widely acknowledge that amyloid is likely one piece of a more complex puzzle.
What’s emerging now is a multi-target approach:
- Anti-amyloid therapies like donanemab and lecanemab clear existing plaques
- Tau-targeting drugs in Phase 2 and 3 trials aim to address the second major protein pathology
- Anti-inflammatory approaches seek to calm the neuroinflammation that accelerates neuronal death
The possibility of combination protocols (pairing plaque removal with tau inhibition or inflammation control) represents the next frontier. Early-stage research suggests multi-target strategies may amplify cognitive preservation beyond what any single drug achieves alone.
Meanwhile, the diagnostic infrastructure is evolving. Blood-based biomarker tests for amyloid and tau are becoming more accessible, potentially replacing expensive PET scans and invasive spinal taps. This could dramatically widen the pool of people who get screened early enough to benefit.
Practical Steps for Families
For anyone navigating early memory changes (whether personally or alongside a loved one), a few concrete considerations stand out:
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Consider specialist evaluation early. A neurologist experienced in dementia can order appropriate biomarker testing. General cognitive screening alone won’t determine treatment eligibility.
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Understand the cost landscape. Donanemab carries an estimated annual cost of approximately $32,000. Medicare covers FDA-approved amyloid-targeting treatments, though prior authorization requirements and infusion center access vary by region.
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Ask about clinical trials. Ongoing studies, including combination therapy trials, may offer access to next-generation approaches. ClinicalTrials.gov remains the most reliable search tool.
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Calibrate expectations honestly. Donanemab slows decline but doesn’t halt or reverse it. Patients still experience progression, just at a reduced pace. Understanding this helps families plan realistically while still embracing genuine hope.
The emotional weight of an Alzheimer’s diagnosis doesn’t shrink because a new drug exists. But having a disease-modifying option (even an imperfect one) changes the calculus of what’s possible.
Donanemab marks a genuine inflection point: the first time Alzheimer’s treatment has moved convincingly from symptom management to biological intervention. The evidence shows meaningful plaque reduction, slowed cognitive decline, and a finite treatment course that distinguishes it from alternatives. None of this equals a cure, and individual outcomes will vary considerably. Yet for families facing early-stage Alzheimer’s, this represents something that didn’t exist five years ago: a treatment that addresses the disease itself. If early memory changes concern you or someone close to you, a conversation with a dementia specialist about biomarker testing is a reasonable and timely next step.
