Last updated Jan. 23, 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) approved Leqembi in January 2023 for the treatment of Alzheimer’s disease under an accelerated approval pathway. 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.
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.
Meanwhile, Eisai has submitted an application requesting the therapy’s approval in the U.S. under a traditional pathway. The company also has submitted a regulatory application seeking Leqembi’s approval in Europe, and has initiated the process in China and Japan.
Who should not take Leqembi?
There are no contraindications for Leqembi’s use.
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 (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.
An ongoing, open-label extension phase of the trial was launched in which all participants received the 10 mg/kg dose for up to two years. One-year data from the extension phase showed the treatment led to rapid and sustained reductions in brain beta-amyloid.
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.
Leqembi also was associated with significant and sustained reductions in amyloid plaques in the brain and slowed disease progression, as assessed by other clinical scales, including ADCOMS.
Findings were generally consistent across patient subgroups, regardless of disease stage, medication use, and genetic status.
An ongoing extension phase of CLARITY AD, in which all participants are receiving Leqembi, is evaluating the treatment’s long-term safety and efficacy.
The global Phase 3 AHEAD 3-45 trial (NCT04468659) is investigating the safety and efficacy of Leqembi in 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.
AHEAD 3-45 is now recruiting up to 1,400 participants at more than 100 study sites worldwide. Top-line data are expected in 2027.
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 participants in the study will be randomly assigned to receive Leqembi in combination with either E2814, or a placebo.
This trial is recruiting adults, ages 18–80, with a known Alzheimer’s-causing genetic mutation, who are cognitively normal or with mild cognitive impairments, at sites in the U.S. Additional sites in Canada and Europe are planned.
Common side effects of Leqembi
The most common side effects associated with Leqembi include:
- infusion-related reactions
- ARIA, or Amyloid Related Imaging Abnormalities, associated with edema (swelling).
Brain imaging abnormalities — ARIA
Some patients treated with Leqembi may experience ARIAs, a known side effect of amyloid-targeted treatment. This may include brain edema (ARIA-E), or hemorrhage (bleeding; ARIA-H).
ARIA is usually asymptomatic and can be detected on an MRI scan. If symptoms do occur, they may include headache, confusion, visual changes, dizziness, nausea, or walking difficulties.
Participants should undergo an MRI scan within a year of starting treatment to assess the presence of existing ARIAs, as well as prior to receiving their fifth, seventh and fourteenth 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 ARIA may be greater in patients carrying two copies of the apolipoprotein E4 genetic variant, the most common genetic risk factor for Alzheimer’s.
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. Pre-medication with antihistamines, anti-inflammatory medications, or corticosteroids may be indicated for some patients for subsequent 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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