The New Alzheimer's Drugs Are Approved. Are They Working?

Key Takeaway: FDA approval of Leqembi and Kisunla does not settle the question of clinical value for individual patients. Plans considering coverage should weigh their limited observed benefit against ARIA risk, MRI monitoring requirements and the full medical cost of treatment.

When the FDA approved lecanemab (Leqembi) in 2023 and donanemab (Kisunla) in 2024, the announcements were framed as major turning points: the first disease-modifying treatments for Alzheimer's disease, a new chapter in a condition that had resisted every prior pharmacological attempt.

For plans and the members who might benefit, that framing carries real weight. But the clinical evidence behind these drugs tells a more complicated story. And the gap between statistical significance and clinical meaning is wide enough that plans can’t afford to treat FDA approval as the end of the analysis.

What These Drugs Do, and What the Trials Showed

Leqembi and Kisunla belong to a class called anti-amyloid monoclonal antibodies. They work by binding to and clearing amyloid-beta plaques in the brain, which are believed to play a central role in Alzheimer's progression. One important distinction: these drugs are approved specifically for patients with mild cognitive impairment or mild dementia due to Alzheimer's, not for moderate or severe disease. The goal is to delay progression, not cure.

In clinical trials, both drugs slowed cognitive decline compared to placebo. The numbers moved in the right direction. The problem is how much they moved.

Clinicians use a threshold called the minimal clinically important difference: the smallest change a patient, or their caregiver, would actually notice in daily life. For Alzheimer's drugs, that threshold is generally considered to be 2 to 3 points on the cognitive scales used in these trials. The improvements observed fell below that, at around 1 point over 76 weeks. Both drugs appear to delay progression by a matter of months. That's not nothing, but it's also not the breakthrough the approval headlines suggested.

When Independent Reviews Reach the Same Conclusion

The Cochrane Collaboration recently published a systematic review covering 17 randomized controlled trials and more than 20,000 participants, including data from both Leqembi and Kisunla alongside other drugs in the same anti-amyloid drug class. The finding: these drugs probably result in little to no difference in cognitive function or dementia severity at 18 months. Successful removal of amyloid from the brain, the review concluded, doesn’t appear to be associated with clinically meaningful effects.

NICE, the UK's health technology assessment body, declined to recommend reimbursement for Leqembi and Kisunla, citing benefits too small to justify the cost of purchasing and administering them. This is a pattern worth paying attention to. Independent clinical and economic reviewers across multiple markets, evaluating the same data the FDA approved, have consistently arrived at the same place.

The Safety and Administrative Burden Plans Need to Understand

These therapies come with a meaningful safety consideration. Both drugs are associated with brain swelling and microbleeds, a side effect class called amyloid-related imaging abnormalities, or ARIA. Most cases are detected only on imaging and cause no symptoms, but serious cases do occur.

Managing that risk requires repeated MRI monitoring throughout treatment. Leqembi and Kisunla are administered intravenously every two to four weeks, which places them in the medical benefit rather than the pharmacy benefit. Infusion center access, nursing staff, and imaging costs are all part of the total picture that won't show up in a pharmacy claims report.

A self-injectable maintenance option for Leqembi was recently approved and may reduce that burden for some patients after an initial IV treatment period, but it does not change the clinical or safety profile of the drug.

Members with a specific genetic variant, APOE epsilon 4, face substantially higher ARIA risk, a factor most benefit programs aren't currently built to screen for.

What Plans Should Do With This

Leqembi and Kisunla have been on the market for only two to three years, and the data is still maturing. A measured, wait-and-see approach is clinically defensible, but that means active oversight, not passive deferral.

The FDA approved these drugs. Independent reviewers across multiple countries evaluated the same data and concluded the benefit is too small relative to the risk and cost. Both positions are grounded in evidence. For plans and brokers, that tension isn't a reason to avoid coverage decisions. It's a reason to make them more carefully: coverage criteria limited to the confirmed appropriate population, MRI monitoring access confirmed before approval, and ongoing evaluation of whether therapy is delivering value over time.

It's also worth watching where the science goes. Researchers are increasingly questioning whether amyloid is the right target for Alzheimer's treatment. If the field shifts, future drugs in this category may look very different. Staying current on how the evidence evolves is part of managing it responsibly.

For plans and brokers, the takeaway is straightforward: FDA approval is the beginning of the coverage conversation, not the end. When the evidence is this contested, clinical oversight isn't optional. It's the only responsible path forward.

FAQs

Who are Leqembi and Kisunla approved for?

Leqembi and Kisunla are approved for patients with mild cognitive impairment or mild dementia due to Alzheimer’s disease. They are not approved for moderate or severe disease.

How much do Leqembi and Kisunla slow Alzheimer’s disease progression?

Clinical trials found that both drugs slowed cognitive decline compared with placebo, but the observed difference was below the threshold generally considered clinically meaningful to patients and caregivers.

What is ARIA, and why does it matter for Alzheimer’s drug coverage?

ARIA, or amyloid-related imaging abnormalities, can involve brain swelling or microbleeds. Because serious cases can occur, patients receiving anti-amyloid therapies require MRI monitoring throughout treatment.

What should health plans consider before covering Leqembi or Kisunla?

Plans should consider clinical eligibility, expected benefit, ARIA risk, access to MRI monitoring, infusion or administration requirements and the full medical cost of treatment.