Last updated July 11, 2023, by Lindsey Shapiro, PhD
Fact-checked by Joana Carvalho, PhD
What is Leqembi for Alzheimer’s disease?
Leqembi (lecanemab), formerly known as BAN2401, is an approved antibody-based therapy for people with Alzheimer’s disease that is designed to prevent the buildup of beta-amyloid protein in the brain and thus slow patients’ cognitive decline.
It was jointly developed by Biogen and Eisai.
How does Leqembi work?
Alzheimer’s disease is characterized by the accumulation of beta-amyloid protein in the brain. The protein forms clumps (plaques) that disrupt nerve cell function and ultimately destroy these neurons.
Leqembi is an antibody that is designed to bind to and neutralize a soluble, toxic version of beta-amyloid. The treatment works by “tagging” the beta-amyloid protein, marking it for clearance by the body’s immune system before it reaches toxic levels.
In doing so, the treatment is thought to be able to slow Alzheimer’s progression, including symptoms of cognitive impairment and functional disability.
Who can take Leqembi?
The U.S. Food and Drug Administration (FDA) granted accelerated approval to Leqembi in January 2023 for the treatment of adults with Alzheimer’s disease. Accelerated approval allows a treatment to be marketed, but a full, traditional approval is contingent on the verification of its clinical benefit in additional trials.
The therapy received full approval in July 2023.The decision made Leqembi the first approved anti-amyloid treatment that was shown to slow disease progression in adults with early Alzheimer’s disease. According to its label, the treatment should be used in patients with mild cognitive impairment or mild dementia; it has not undergone clinical testing in patients at other disease stages.
Eisai has submitted regulatory applications seeking Leqembi’s approval for the same indication in the European Union, the U.K., Canada, Japan, China, and South Korea.
Who should not take Leqembi?
Leqembi is not recommended for anyone with a known serious allergy to the medication or any of its ingredients.
Patients carrying two copies of a gene variant called APOE4, the strongest genetic risk factor for Alzheimer’s, are at a higher risk of amyloid-related imaging abnormalities, a known, potentially life-threatening side effect of amyloid-reducing antibodies like Leqembi. Therefore, patients should be tested for the variant prior to initiating treatment with Leqembi. A decision to start the treatment should be discussed with physicians based on the therapy’s benefits and a patient’s risk of developing such abnormalities.
How is Leqembi administered?
Leqembi comes as a clear to opalescent and colorless to pale yellow liquid that is diluted in a saline solution at the appropriate dose by a healthcare provider prior to administration.
It is given by a healthcare provider as an intravenous (into-the-vein) infusion at a dose of 10 mg/kg of body weight, once every two weeks. Each infusion takes about an hour.
The presence of beta-amyloid aggregates in the brain should be confirmed prior to the start of treatment.
Leqembi in clinical trials
Applications seeking Leqembi’s approval were supported by data from a Phase 2b trial called Study 201, and a Phase 3 trial called Clarity AD.
STUDY 201
Study 201 (NCT01767311) was a large trial that examined the effectiveness and safety of Leqembi, given intravenously once or twice per month, at one of three possible doses, against a placebo. The trial enrolled more than 800 people with early Alzheimer’s.
Results showed that Leqembi at its highest dose (10 mg/kg twice monthly) led to a statistically significant 30% decrease in cognitive decline after 18 months, or about 1.5 years. These benefits, as assessed by the Alzheimer’s Disease Composite Score (ADCOMS), were observed as early as six months after treatment initiation.
Treatment also eased beta-amyloid accumulation in the brain — measured with a PET scan — relative to a placebo over the 18-months trial. About 81% of Leqembi-treated patients converted from amyloid-positive to amyloid-negative by the end of the trial.
Participants completing the 18-month placebo-controlled period could enter the study’s open-label extension phase, in which all receive the 10 mg/kg dose for up to two years.
CLARITY AD
Clarity AD (NCT03887455), which evaluated Leqembi at its 10 mg/kg dose against a placebo, involved 1,795 people with early Alzheimer’s, treated for 1.5 years. The trial’s main goal was to evaluate changes in dementia symptoms, as assessed with the Clinical Dementia Rating-Sum Boxes (CDR-SB) scale.
Full study results showed that Leqembi led to a significant 27% slowing of cognitive decline compared with the placebo group. While those in the Leqembi group experienced a mean 1.21-point increase in CDR-SB scores over the trial — reflecting dementia progression — those on a placebo saw a greater increase of 1.66 points.
Full study results showed that Leqembi significantly slowed dementia progression by 27%, when compared with a placebo. While those in the Leqembi group experienced a mean 1.21-point increase in CDR-SB scores over the trial — reflecting dementia worsening — those on a placebo saw a greater increase, of 1.66 points.
Leqembi-treated patients also showed a 24% slower cognitive decline, as assessed with ADCOMS, and a 37% slower decline in the ability to do activities of daily living such as eating, dressing, or socializing relative to those on a placebo. The therapy also was associated with significant and sustained reductions in amyloid plaques in the brain.
Patients who completed the placebo-controlled part of CLARITY AD were given the choice to enter the trial’s open-label extension phase, in which all are receiving Leqembi to evaluate the treatment’s long-term safety and efficacy.
Ongoing trials
The global Phase 3 AHEAD 3-45 trial (NCT04468659) is investigating the safety and efficacy of Leqembi in up to 1,400 adults, ages 55-80, with preclinical Alzheimer’s disease — those with elevated levels of beta-amyloid in the brain, but without overt symptoms of the disease.
The Phase 2/3 DIAN-TU trial (NCT05269394) is investigating the safety and efficacy of Leqembi in combination with an anti-tau antibody (E2814) as a potential treatment for Alzheimer’s. Tau is another protein that builds up to toxic levels in people with Alzheimer’s.
Up to 168 adults, ages 18-80, with a known Alzheimer’s-causing genetic mutation and who are cognitively normal or have mild cognitive impairments, will be randomly assigned to receive Leqembi in combination with either E2814 or a placebo.
Common side effects of Leqembi
- infusion-related reactions
- amyloid-related imaging abnormalities, or ARIAs, associated with brain bleeds and/or swelling
- headache.
Brain imaging abnormalities — ARIA
Leqembi’s label carries a boxed warning for ARIAs, a known side effect of amyloid-targeting antibody-based therapies that can cause brain swelling or edema (ARIA-E); and/or brain bleeding or hemorrhage (ARIA-H). These abnormalities also can occur spontaneously in Alzheimer’s patients.
ARIAs usually occur early after the start of treatment and while they typically do not result in symptoms, they can be detected on an MRI scan. If symptoms do occur, they may include headache, confusion, visual changes, dizziness, nausea, and/or walking difficulties. In rare cases, ARIAs can be life threatening, so patients should be monitored for these brain abnormalities before and during Leqembi treatment.
Patients should undergo an MRI scan before starting Leqembi treatment to assess the presence of existing ARIAs, as well as prior to receiving their fifth, seventh, and 14th treatment infusions. Enhanced vigilance for ARIAs is recommended during the first 14 weeks of treatment.
If a patient experiences signs of ARIA, a decision on whether treatment should continue will be determined by a healthcare provider based on the severity of the symptoms and/or MRI abnormalities.
The risk of ARIAs, including those causing symptoms and those considered serious, is greater in patients carrying two copies of the APOE4 gene variant. As such, genetic testing for the variant should be performed before initiating Leqembi treatment to assess a patient’s risk of developing ARIAs. Patients and their healthcare teams should discuss the therapy’s benefits as well as its ARIA-associated risks when deciding whether to start treatment with Leqembi.
Allergic reactions
Treatment with Leqembi may cause allergic reactions, including those leading to tissue swelling and airway muscle tightening. Serious allergic reactions have been reported in patients receiving Leqembi. The therapy should never be given to anyone with a history of serious allergy to its ingredients.
If any signs or symptoms of an allergic reaction occur, such as swelling of the face, extremities, eyes, lips, tongue, and/or difficulty in swallowing or breathing, Leqembi infusion should be stopped immediately and appropriate treatment should be initiated.
Infusion-related reactions
Some patients may experience reactions to Leqembi infusions, which most commonly include fever, flu-like symptoms, nausea, vomiting, blood pressure changes, and low oxygen levels.
For patients who experience a reaction, the infusion may be slowed or stopped. Preventive treatment with antihistamines, anti-inflammatory medications, or corticosteroids may be indicated for some patients before additional infusions after discussion with their healthcare provider.
Use in pregnancy and breastfeeding
Clinical trials did not include pregnant women and no animal studies have been conducted to assess the potential reproductive or developmental toxicity of Leqembi. Patients who are pregnant or wish to become pregnant while using the treatment should talk with their healthcare team.
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