Alzheimer's Disease Medications: Do the Benefits Outweigh the Risks?

Currently, two FDA-approved medications are designed to modify the progression of Alzheimer’s disease: Kisunla (donanemab) and Leqembi (lecanemab). Aduhelm (aducanumab), another medication in this class, was discontinued in 2024.

Although these medications have demonstrated some ability to slow cognitive and functional decline in certain patients, their benefits must be weighed against their potential risks, including serious brain-related side effects.

Let’s take a closer look at the clinical evidence, safety concerns, and costs associated with these treatments.

Kisunla: What Does the Clinical Evidence Show?

A Phase 2 clinical trial funded by Kisunla’s manufacturer, Eli Lilly, evaluated the medication’s effectiveness and safety in patients with early Alzheimer’s disease.

The trial met its primary objective, demonstrating a statistically significant improvement in the Integrated Alzheimer’s Disease Rating Scale (iADRS) compared with placebo after the treatment period. The iADRS is a tool used to assess both cognitive abilities and daily functioning.

At the primary analysis, patients receiving Kisunla experienced less decline than those receiving placebo. However, the results across several important secondary measures were less conclusive.

What About the Secondary Outcomes?

Researchers also evaluated changes in several established measures of Alzheimer’s disease progression, including:

• Clinical Dementia Rating Scale–Sum of Boxes (CDR-SB): Assesses cognitive and functional impairment.
• Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog13): Measures changes in cognitive performance.
• Alzheimer’s Disease Cooperative Study–Instrumental Activities of Daily Living Inventory (ADCS-iADL): Evaluates a person’s ability to perform everyday tasks.
• Mini-Mental State Examination (MMSE): Assesses overall cognitive function.

The Phase 2 results did not demonstrate consistent, statistically significant benefits across these secondary outcomes. This raised questions about the extent of Kisunla’s clinical benefits beyond its primary endpoint.

The study also did not establish significant improvements in certain imaging-based measures, including brain volume, compared with placebo.

The investigators concluded that longer and larger clinical trials were needed to further evaluate donanemab’s efficacy and safety in Alzheimer’s disease.

What Did the Larger Phase 3 Trial Find?

The subsequent Phase 3 trial, known as TRAILBLAZER-ALZ 2, provided additional evidence regarding Kisunla’s effects.

After 76 weeks of treatment, researchers found that Kisunla slowed clinical decline compared with placebo in participants with early symptomatic Alzheimer’s disease. The trial demonstrated statistically significant benefits on measures of cognition and daily functioning, although the degree of benefit varied depending on the outcome and the patient population studied.

The important distinction is that slowing disease progression is not the same as reversing Alzheimer’s disease or restoring lost cognitive function. For patients and families, even a modest slowing of decline may be meaningful, but the potential benefit must be considered alongside the risks.

Kisunla Safety: What Are the Concerns?

Kisunla is administered by intravenous infusion. Common adverse effects include infusion-related reactions and headache.

More serious concerns involve amyloid-related imaging abnormalities (ARIA) , which may include:

• ARIA-E: Brain swelling or fluid accumulation.
• ARIA-H: Small areas of bleeding or other blood-related changes in the brain, including microhemorrhages.

These abnormalities may be asymptomatic, but some can cause serious neurological complications and, in rare cases, can be fatal.

In the TRAILBLAZER-ALZ 2 trial:

• 36.8% of participants receiving Kisunla experienced ARIA, compared with 14.9% receiving placebo.
• 26.8% of participants receiving Kisunla experienced ARIA-H, compared with 12.5% receiving placebo.
• People carrying two copies of the APOE ε4 genetic variant had a particularly high risk of ARIA.

Three deaths in the trial were considered related to treatment-associated ARIA.

These findings highlight the importance of discussing individual risk factors, reviewing relevant genetic considerations, and following recommended MRI monitoring protocols before and during treatment.

What About European Regulatory Approval?

Kisunla’s regulatory history also reflects concerns about its benefit-risk profile. The European Medicines Agency initially recommended against authorizing Kisunla in 2024, citing concerns about the balance between its benefits and risks. The European Commission subsequently authorized the medication in 2025 for a restricted group of patients with early Alzheimer’s disease who have one or no copies of the APOE ε4 gene.

This illustrates an important point: regulatory agencies may reach different conclusions depending on their assessment of the evidence, patient selection, and safety precautions.

Is Leqembi a Safer Alternative?

Leqembi (lecanemab) is another anti-amyloid medication approved to slow the progression of early Alzheimer’s disease. Like Kisunla, it targets amyloid-beta in the brain and has demonstrated modest slowing of cognitive and functional decline in clinical trials.

However, Leqembi also carries a risk of ARIA, including potentially serious or fatal complications.

The FDA approved Leqembi in 2023 and required a boxed warning regarding the risk of ARIA. Patients and clinicians must consider these risks when deciding whether treatment is appropriate.

Emerging Safety Concerns With Leqembi

A post-marketing analysis published in January 2025 examined adverse-event reports associated with lecanemab and identified safety signals warranting further investigation. The analysis also reported events, including tremor, migraine, and pancreatic cancer, that had not been identified as established adverse reactions in the clinical trials.

It is important to distinguish between an adverse event reported after a medication is used and an adverse effect proven to have been caused by that medication. Post-marketing reports can identify potential safety signals, but additional research is needed to establish whether such events are causally related to treatment.

In August 2025, the FDA also raised concerns about serious ARIA events occurring early in treatment. Following reports of early deaths and serious ARIA cases before the fifth infusion, the agency recommended additional early MRI monitoring to help identify these complications.

These developments reinforce the importance of careful patient selection, appropriate monitoring, and an informed discussion of the potential benefits and risks.

How Much Do These Treatments Cost?

The financial commitment associated with Alzheimer’s disease medications is another important consideration.

Estimated medication costs include:

• Kisunla: Approximately $12,500 for six months, $32,000 for 12 months, and more than $48,000 for 18 months.
• Leqembi: Approximately $26,500 for 12 months.

These figures are estimates and may change over time. Actual costs depend on insurance coverage, treatment duration, infusion services, MRI monitoring, and other medical expenses. Patients should confirm current pricing and coverage with their insurer and treatment provider.

Making an Informed Decision About Alzheimer’s Disease Treatment

When considering a treatment intended to slow Alzheimer’s disease progression, patients and their families deserve a clear understanding of the potential benefits, risks, monitoring requirements, and financial costs.

For some patients, these medications may offer a meaningful opportunity to slow clinical decline. For others, individual risk factors, existing health concerns, treatment burden, or personal preferences may lead them to consider different approaches to care.

Already taking Kisunla or Leqembi and concerned about potential side effects? Or have you been offered one of these medications and want to better understand your options?

At Valley Integrative Health , we offer early screening, thorough assessment, and comprehensive, evidence-informed care for individuals concerned about Alzheimer’s disease and cognitive health.

Our goal is to help patients better understand their health, explore appropriate options, and make informed decisions in collaboration with their healthcare providers.