Leqembi (Lecanemab) vs Donanemab For Alzheimer’s: What’s The Difference?

Dive into the differences between Leqembi (lecanemab) & Donanemab to better determine which is best for you. 

Alzheimer's disease continues to pose a significant healthcare challenge, which has led to the relentless search for effective Alzheimer's drugs. 

According to the National Institute on Aging and the Alzheimer’s Association Research Framework, abnormal β-amyloid is a key pathological hallmark of Alzheimer's disease. β-amyloid, also known as beta-amyloid, is a protein fragment that tends to accumulate and form sticky plaques outside the neurons of the brain. The accumulation of this plaque disrupts communication between neurons, which is why it’s one of the major targets in Alzheimer's disease drug development. 

Leqembi (lecanemab) and donanemab are two such medications that help with early-stage Alzheimer's disease. Below, we dive into the differences between these two drugs to help you better determine which is best for you.

About lecanemab

Manufactured by Biogen and Eisai, lecanemab is a monoclonal antibody that targets soluble aggregated Aβ species such as monomers, oligomers, insoluble fibrils in plaques, and protofibrils. Soluble aggregated Aβ species are forms of β-amyloid (Aβ) peptides that have the tendency to clump together and form aggregates, leading to the formation of insoluble plaques in the brains of those with Alzheimer's disease.

Research has shown that lecanemab is effective in reducing robust brain fibrillar amyloid and slowing clinical decline in early Alzheimer’s disease (“early” meaning mild cognitive impairment or mild dementia).

READ MORE: Leqembi (Lecanemab) Is Now Approved For Alzheimer's Treatment: What To Know

About donanemab

Donanemab (N3pG) is a monoclonal antibody that recognizes the Aβ found in amyloid plaques. Unlike other Alzheimer's medications that work to prevent the deposition of new plaques or the growth of existing plaques, donanemab targets the deposited plaque and works to clear the existing amyloid plaques in the brain.

Top-line differences between lecanemab and donanemab

While donanemab and lecanemab are both monoclonal antibodies that target amyloid-beta (Aβ) plaques, the main difference is that they target them at different stages as they build up in the brain. Lecanemab targets amyloid-beta (Aβ) plaques as it proceeds to form fibers, whereas donanemab binds itself to the plaques when the fibers have clumped together to become a larger plaque in the brain.  

Another major difference between these two medications is that, although they are both given as intravenous infusions based on the weight of the patients, lecanemab is given every 2 weeks while donanemab is given every 4 weeks. 

Are both lecanemab and donanemab FDA-approved?

The U.S. Food and Drug Administration approved Lecanemab in January 2023 for the treatment of Alzheimer’s disease through the Accelerated Approval Pathway, which expedites the approval of medications for a serious medical condition with unmet treatment needs.

Although  Eli Lily’s donanemab has been found effective for reducing amyloid plaque in the early stages of Alzheimer’s disease — and the FDA considers amyloid plaque reduction to be a valid Alzheimer’s biomarker — the medication has not yet received FDA approval. 

Efficacy: Does lecanemab work as well as donanemab?

In the phase 3 trials for early Alzheimer’s disease, CLARITY-AD for lecanemab and TRAILBLAZER-ALZ2 for donanemab, it was found that these two medications resulted in the slowing of cognitive decline and positive alterations on specific biomarkers of Alzheimer’s disease. 

According to results from a landmark study, Eli Lilly’s donanemab slowed cognitive and functional decline in Alzheimer’s patients by 35%. This was measured using the Integrated Alzheimer’s Disease Rating Scale (iADRS).

Results from Eisai and Biogen’s lecanemab trial show that it reduces the rate of Alzheimer’s disease by 27%. 

What is the cost difference between lecanemab and donanemab?

Lecanemab costs $26,500 per year. 

Since donanemab is not yet on the market, there's not a specific price for it yet, but there are speculations by the manufacturers that it will likely be around the same price as lecanemab. 

How long it takes for lecanemab and donanemab to work

According to lecanemab’s Phase 3 trial, amyloid reduction is achieved within 3 months of treatment and clinical benefits within 6 months of treatment. In the research, more than 80% of subjects were amyloid negative (by visual reading) within 12–18 months of treatment in comparison to the placebo treatment.

Research shows that, in early Alzheimer’s disease, donanemab resulted in a decrease of  amyloid plaque by 24 weeks, and 68% of those who received donanemab were  "amyloid-negative" — meaning their amyloid plaque level was below 24.1 CL (complete amyloid clearance) — by the 76-week mark.

Side effects of lecanemab and donanemab

Side effects of lecanemab

Infusion-related reactions

Lecanemab may result in severe reactions during or after infusion, including:

• Chills
• Fever
• Lightheadedness or dizziness
• Nausea
• Vomiting 
• Racing heart or chest pounding 
• Shortness of breath or difficulty breathing
• Joint pain 
• Body aches

You should inform your healthcare provider if you experience any of the above reactions. Your doctor may also give you medications that may prevent a reaction before starting the treatment. 

Serious side effects

Lecanemab may cause serious side effects like Amyloid Related Imaging Abnormalities or “ARIA.” 

ARIA is an adverse event that manifests in two distinct types: 

1. 1) ARIA-E, characterized by parenchymal or pial edema
2. ARIA-hemorrhage (ARIA-H), which involves hemosiderin deposition in the form of superficial siderosis or hemorrhage

It is mostly seen as temporary swelling in some parts of the brain which resolves over time. Some patients may have small spots of bleeding in or on the surface of their brain, and sometimes there might be larger areas of brain bleeding. Patients who experience this type of swelling in their brain are typically asymptomatic.

If ARIA is symptomatic, signs and symptoms may include:

• Headache 
• Confusion 
• Difficulty walking 
• Dizziness
• Seizures
• Vision changes 

Having the genetic risk factor (homozygous apolipoprotein E gene carriers) may result in an increased risk for experiencing ARIA. There are also medications that can increase the risk for larger areas of bleeding in the brain in patients receiving lecanemab. Your healthcare provider will check to see if you are on any medications that may increase the risk and also carry out magnetic resonance imaging (MRI) scans before and frequently throughout your treatment to check for ARIA.

Side effects of donanemab 

Patients may experience infusion-related reactions when receiving donanemab, but the specific reactions it may cause have not been disclosed yet. 

According to its trial, donanemab may result in changes in the brain known as amyloid-related imaging abnormalities (ARIA) which can be discovered through an MRI.  In the TRAILBLAZER-ALZ clinical trial results, 38.9% of patients had amyloid-related imaging abnormalities. 

In the clinical trial, 27.5% of the patients who received donanemab experienced ARIA-E while 30.5% had ARIA-H. There was also a 0.8% incidence of ARIA-E in the placebo group and a 7.2% incidence of ARIA-H in the placebo group.

Safety: Is lecanemab a safe alternative to donanemab and vice-versa? 

In the phase 3 trials, the reported rates of ARIA were slightly higher for donanemab (ARIA-E 24.0%, ARIA-H 31.4%) compared to lecanemab (ARIA-E 12.6%, ARIA-H 17.3%).

READ MORE: Leqembi (Lecanemab) vs Aduhelm (Aducanumab) For Alzheimer's: What's The Difference? 

Interested in learning more about Alzheimer’s treatment at Local Infusion?

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From questions on what to expect in your first treatment, to providing financial guidance and support, a dedicated Infusion Guide works with you and your physician to provide clear answers and assistance every step of the way. Plus, we take care of everything having to do with prior authorization. 

We’ll reach out within hours of a physician referral and get you digitally on board in less than two minutes, allowing our staff more time to focus on you.

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