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

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Discover the differences between these two drugs to better determine which is best for you.

Alzheimer’s disease is a debilitating condition that affects millions of people. 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 disrupts communication between neurons, which is why it’s one of the major targets in Alzheimer's disease drug development. 

Leqembi (lecanemab) and Aduhelm (aducanumab) don't cure or reverse Alzheimer’s disease, but they are anti-amyloid treatments that reduce the presence of beta-amyloid plaques in the brain.

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 a structure of a beta-amyloid called N3pG, which helps in the formation of amyloid plaques in the brain.

Lecanemab 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).

About aducanumab

Aducanumab is an amyloid beta-directed monoclonal antibody. It was found effective in people living with early Alzheimer’s disease, mild cognitive impairment (MCI), or mild dementia due to Alzheimer's disease, or those with amyloid plaques buildup in their brain.

Top-line differences between lecanemab and aducanumab

The main difference between lecanemab and aducanumab is that lecanemab primarily focuses on Aβ protofibrils, while aducanumab focuses on highly aggregated forms of Aβ. Another major difference is with their mechanism of action. Aducanumab removes beta-amyloid from the brain while lecanemab blocks the formation of amyloid plaques in the brain.

Are both lecanemab and aducanumab FDA-approved?

Lecanemab and aducanumab have both received approval from the US Food and Drug Administration (FDA). 

In 2021, the FDA approved aducanumab through the Accelerated Approval Pathway. 

In January 2023, lecanemab received FDA approval based on Clarity AD, where lecanemab met the primary endpoint and all key secondary endpoints with statistically significant results. “Endpoint” here refers to the specific outcome or result that was used to assess the effectiveness of a medication during a clinical trial. Lecanemab was also approved through the Accelerated Approval Pathway. 

Efficacy: Does lecanemab work as well as aducanumab?

Aducanumab showed significant slowing of cognitive decline in patients with early-stage disease in one of two of the phase 3 clinical trials. 

Lecanemab has a comparable efficacy as aducanumab, as measured by the Clinical Dementia Rating-Sum of Boxes (CDR-SB). This is the measurement tool used in clinical trials to assess the severity of dementia in individuals with Alzheimer's disease and other forms of dementia

One of the reasons why lecanemab is beneficial is its binding profile. Lecanemab focuses on targeting Aβ protofibrils, while aducanumab and other medications like gantenerumab target highly aggregated forms of Aβ. This different target focus makes lecanemab more effective and safer — lecanemab results in a substantially lower incidence of amyloid-related imaging abnormalities such as transient immunotherapy-related-brain oedema and microbleeds. 

What is the cost difference between lecanemab and aducanumab?

Lecanemab costs $26,500 for a year's worth of treatment while aducanumab costs $28,200. Keep in mind that the amount a patient eventually pays will depend on their insurance policies or whether they use services like Medicare. 

How long it takes for lecanemab and aducanumab 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.

According to aducanumab clinical trials, it takes ~18 months to reduce amyloid plaque levels — although it’s important to note that aducanumab is a long-term drug, so if it’s effective your doctor may have you take it for a longer period. 

Side effects of lecanemab and aducanumab

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. 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 during your treatment to check for ARIA.

Side effects of aducanumab

Mild side effects 

Aducanumab may cause some mild side effects, including: 

  • Headache
  • Diarrhea
  • Upper respiratory tract infection
  • Confusion
  • Disorientation 

These side effects may stop within a few days or a couple of weeks.

Serious allergic reactions 

Aducanumab may cause some serious allergic reactions during or after an infusion, including: 

  • Hives
  • Swelling of the face, mouth, lips, or tongue

You should inform your healthcare provider if you experience any of the symptoms of a serious allergic reaction during or after an infusion.

Also, during an aducanumab infusion, hypersensitivity reactions such as angioedema or urticaria may occur, in which case your provider will immediately discontinue treatment. 

Serious side effects

Aducanumab may also cause ARIA. 

To ensure your safety during aducanumab treatment, your healthcare provider will conduct baseline magnetic resonance imaging (MRI) scans before you start and periodic MRI scans during the course of treatment to monitor any potential occurrence of ARIA.

Safety: is lecanemab a safe alternative to aducanumab and vice-versa? 

There is a substantially lower incidence of amyloid related imaging abnormalities with lecanemab. This is because lecanemab mainly targets Aβ protofibrils, while aducanumab and other medications like gantenerumab targets highly aggregated forms of Aβ.

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

Local Infusion offers modern, state-of-the-art centers with private suites, designed with your comfort in mind.

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.

Should you have questions regarding pricing and insurance, our team will work with you to provide financial assistance support and minimize costs, providing a simple and stress-free experience.

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