Source: European Medicines Agency (EU) Revision Year: 2025 Publisher: Eisai GmbH, Edmund-Rumpler-Straße 360549 Frankfurt am Main, Germany, e-mail: medinfo_de@eisai.net
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Patients with bleeding disorders that are not under adequate control.
Pre-treatment MRI findings of prior intracerebral haemorrhage, more than 4 microhaemorrhages, superficial siderosis or vasogenic oedema, or other findings, which are suggestive of cerebral amyloid angiopathy (CAA) (see section 4.4).
Treatment with lecanemab should not be initiated in patients receiving ongoing anticoagulant therapy (see section 4.4).
In order to promote the safe and effective use of lecanemab, initiation of treatment in all patients should be through a central registration system implemented as part of a controlled access programme.
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Hypersensitivity reactions, including angioedema, bronchospasm, and anaphylaxis, have occurred in patients who were treated with lecanemab which may be serious. Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity-type reaction, and initiate appropriate therapy (see section 4.2).
The presence of amyloid beta pathology must be confirmed via an appropriate test prior to initiating treatment.
ARIA can occur spontaneously in patients with Alzheimer’s disease. ARIA-H generally occurs in association with an occurrence of ARIA-E.
ARIA usually occurs early in treatment and is usually asymptomatic, although serious and life-threatening events, including seizure and status epilepticus, rarely can occur. When present, reported symptoms associated with ARIA may include headache, confusion, visual changes, dizziness, nausea, and gait difficulty. Focal neurologic deficits may also occur. In patients who experienced ARIA on placebo or with lecanemab, ⅓ experienced recurrent ARIA. Following an initial event of ARIA, the rate of recurrence on resumption of treatment with lecanemab is very common (see section 4.8). Symptoms associated with ARIA usually resolve over time (see section 4.8).
The risk of ARIA, including symptomatic and serious ARIA, is increased in apolipoprotein E ε4 (ApoE ε4) homozygote carriers (see section 4.8). In addition to ARIA, intracerebral haemorrhages greater than 1 cm in diameter have occurred in patients treated with lecanemab.
Consider the benefit of lecanemab for the treatment of Alzheimer’s disease and potential risk of serious adverse events associated with ARIA when deciding to initiate treatment with lecanemab (see section 4.8).
Baseline brain MRI and periodic monitoring with MRI are recommended. Enhanced clinical vigilance for ARIA is recommended during the first 14 weeks of treatment with lecanemab. If a patient experiences symptoms suggestive of ARIA (see section 4.8), clinical evaluation should be performed, including additional MRI testing (see section 4.2).
The radiographic severity of ARIA associated with lecanemab was classified by the criteria shown in Table 1.
Table 1. ARIA MRI Classification Criteria:
| ARIA Type | Radiographic Severity1 | ||
|---|---|---|---|
| Mild | Moderate | Severe | |
| ARIA-E | FLAIR hyperintensity confined to sulcus and/or cortex/subcortex white matter in one location <5 cm | FLAIR hyperintensity 5 to 10 cm in single greatest dimension, or more than 1 site of involvement, each measuring <10 cm | FLAIR hyperintensity >10 cm with associated gyral swelling and sulcal effacement. One or more separate/independent sites of involvement may be noted. |
| ARIA-H microhaemorrhage | ≤4 new incident microhaemorrhages | 5 to 9 new incident microhaemorrhages | 10 or more new incident microhaemorrhages |
| ARIA-H superficial siderosis | 1 focal area of superficial siderosis | 2 focal areas of superficial siderosis | >2 areas of superficial siderosis |
1 Radiographical severity is defined by the total number of new microhaemorrhages from baseline or total number of areas for superficial siderosis.
For patients with asymptomatic radiographic findings of ARIA-E, enhanced clinical vigilance for symptoms of ARIA is recommended (see section 4.8 for symptoms). Obtain additional MRIs after 1 to 2 months to assess for resolution, or sooner if symptoms present.
Patients treated with lecanemab who are ApoE ε4 homozygote carriers have a higher incidence of ARIA, including symptomatic serious and recurrent ARIA, compared to heterozygote carriers and non-carriers (see section 4.8). Lecanemab is not indicated for use in patients who are homozygotes (see section 4.1).
Caution should be exercised when considering the use of lecanemab in patients with factors that indicate an increased risk for intracerebral haemorrhage.
Intracerebral haemorrhages greater than 1 cm in diameter including fatal events have been observed in patients taking both lecanemab and anticoagulants or in patients receiving thrombolytic agents during lecanemab treatment. Additional caution should be exercised when considering the administration of anticoagulants to a patient already being treated with lecanemab.
Baseline use of antithrombotic medicinal products (aspirin, other antiplatelets, or anticoagulants) was allowed in clinical trials if the patient was on a stable dose. The majority of exposures to antithrombotic medications were to aspirin. An increased risk of ARIA or intracerebral haemorrhage was not observed with antiplatelet use.
Because intracerebral haemorrhages have been observed in patients taking both lecanemab and anticoagulants (see section 4.8), and in patients receiving thrombolytic agents during lecanemab treatment, additional caution should be exercised when considering the administration of anticoagulants or a thrombolytic agent (e.g. tissue plasminogen activator) to a patient already being treated with lecanemab:
Treatment with lecanemab should not be initiated in patients receiving ongoing anticoagulant therapy (see section 4.3).
Patients were excluded from enrolment in Study 301 for findings on neuroimaging that indicated an increased risk for intracerebral haemorrhage. These included findings suggestive of CAA (prior cerebral haemorrhage greater than 1 cm in greatest diameter, more than 4 microhaemorrhages, superficial siderosis, vasogenic oedema) or other lesions (aneurysm, vascular malformation) that could potentially increase the risk of intracerebral haemorrhage.
The presence of an ApoE ε4 allele is associated with CAA, which has an increased risk for intracerebral haemorrhage.
Infusion related reactions were observed in clinical trials with lecanemab (see section 4.8); the majority were mild or moderate and occurred with the first infusion. In the event of an infusion-related reaction, the infusion rate may be reduced, or the infusion may be discontinued, and appropriate therapy initiated as clinically indicated. Prophylactic treatment with antihistamines, acetaminophen, nonsteroidal anti-inflammatory drugs, or corticosteroids prior to future infusions may be considered.
Patients with a history of transient ischemic attacks (TIA), stroke or seizures within 12 months of screening were excluded in the clinical trials with lecanemab. The safety and efficacy in these patients are unknown.
Patients with immunologic disorders who were not adequately controlled or required therapy with immunoglobulins, systemic monoclonal antibodies, systemic immunosuppressants or plasmapheresis were excluded in the clinical trials with lecanemab, hence the safety and efficacy in these patients are unknown.
Patients with autosomal dominant Alzheimer’s disease or with Down syndrome may be associated with a higher rate of CAA and ARIA events and have been excluded from clinical trials with lecanemab. The safety and efficacy of lecanemab in these patients are unknown.
The prescriber must discuss the risks of lecanemab therapy, MRI scans and signs or symptoms of adverse reactions and when to seek attention from a healthcare professional with the patient. The patient will be provided with the patient card and instructed to carry the card at all times.
Dilution with sodium chloride (0.9% saline) is necessary before administration. See the product information for the sodium chloride diluent for information.
This medicine contains 0.5 mg of polysorbate 80 in each 1 mL of lecanemab. Polysorbates may cause allergic reactions. Patients with known allergies shall be taken into consideration.
No drug interaction studies have been conducted with lecanemab.
Elimination of lecanemab is likely to occur through normal degradation pathways for immunoglobulins and the clearance should not be affected by small molecule concomitant medications. Therefore, it is not expected that lecanemab will cause or be susceptible to pharmacokinetic (PK) drug interactions with concomitantly administered agents.
The risk of intracerebral haemorrhage with lecanemab treatment may be increased in patients receiving anticoagulant therapy or thrombolytic agents (see sections 4.3 and 4.4).
Pregnancy status of females of child-bearing potential should be verified prior to initiating treatment with lecanemab.
Women of childbearing potential should use effective contraception during treatment and for 2 months after the last dose of lecanemab.
There are no data on the use of lecanemab in pregnant women or animal data to assess the risk of lecanemab during pregnancy. Human IgG is known to cross the placenta after the first trimester of pregnancy. Therefore, lecanemab has the potential to be transmitted from the mother to the developing foetus. The effects of lecanemab on the developing foetus are unknown. Lecanemab is not recommended during pregnancy.
There are no data on the presence of lecanemab in human milk, the effects on the breast-fed infants, or the effects of the drugs on milk production.
Human IgG is known to be excreted in breast milk during the first days after birth, which is decreasing to low concentrations soon afterwards. The effects of this exposure to breastfed infant are unknown and a risk cannot be excluded. Therefore, a decision should be made whether to discontinue breast-feeding or to discontinue lecanemab, taking into account the benefit of breast-feeding for the child and the benefit of lecanemab therapy for the woman.
There are no data on the effects of lecanemab on human fertility.
Lecanemab has no or negligible influence on the ability to drive and use machines. Patients should be advised to use caution when driving or operating machinery in case they experience dizziness or confusion during treatment with lecanemab.
The safety of lecanemab has been evaluated in 2203 patients who received at least one dose of lecanemab.
In the double-blind, placebo-controlled period of Study 301 in patients with mild cognitive impairment due to Alzheimer’s disease or mild Alzheimer’s disease dementia, a total of 898 patients received lecanemab at the recommended dose of 10 mg/kg every 2 weeks, of which 757 patients were non-carriers or heterozygotes (the indicated population).
Of the patients treated with lecanemab 31% (278/898) were non-carriers, 53% (479/898) were heterozygotes and 16% (141/898) were homozygotes. With the exception of events of ARIA, the safety profile was the same across genotypes.
Seizures including status epilepticus have been reported with lecanemab treatment in the clinical trials.
In the indicated population, the most common adverse reactions were infusion-related reaction (26%), ARIA-H (13%), headache (11%) and ARIA-E (9%).
Intracerebral haemorrhages greater than 1 cm in diameter were reported in 0.5% (4/757) patients in Study 301 after treatment with lecanemab compared to 0.1% (1/764) patients on placebo. Fatal events of intracerebral haemorrhage in patients receiving lecanemab have been observed.
The following adverse reactions listed in Table 2 below have been reported in clinical trials with lecanemab.
The adverse reactions are presented as MedDRA preferred terms under the MedDRA System Organ Class. Adverse reactions are ranked according to system organ class, using the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1 000 to <1/100), rare (≥1/10 000 to <1/1 000), very rare (<1/10 000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Table 2. Adverse reactions:
| System Organ Class (SOC) | Adverse reaction | Frequency category |
|---|---|---|
| Immune system disorders | Hypersensitivity reactions1 | Common |
| Delayed hypersensitivity reactions2,3 | Common | |
| Nervous system disorders | Headache | Very Common |
| ARIA4 | Very Common | |
| ARIA-H5,6 | Very Common | |
| Symptomatic ARIA-H7 | Common | |
| Cerebral microhaemorrhage ≤10 | Very Common | |
| Cerebral microhaemorrhage >10 | Common | |
| Superficial siderosis | Common | |
| Intracerebral haemorrhage >1 cm | Uncommon | |
| ARIA-E8,9 | Common | |
| Symptomatic ARIA-E7 | Common | |
| Cardiac disorders | Atrial fibrillation | Common |
| Gastrointestinal disorders | Nausea | Common |
| General disorders and administration site conditions | Infusion related reactions10 | Very Common |
1 Includes angioedema, bronchospasm, anaphylaxis, rash and headache.
2 Includes rash, headache, rhinorrhoea, rhinitis and hair loss.
3 Occurred 24 hours after infusion.
4 ARIA: Includes radiographic ARIA-E, symptomatic ARIA-E, radiographic ARIA-H and symptomatic ARIA-H.
5 ARIA-H: Includes radiographic ARIA-H and symptomatic ARIA-H.
6 ARIA-H: Amyloid related imaging abnormality-microhaemorrhage and haemosiderin deposit; Superficial siderosis of central nervous system, and Cerebellar microhaemorrhage.
7 Includes common symptom of headache; uncommon symptoms of confusion, visual changes (diplopia, glare, vision blurred, visual acuity reduced, visual impairment), dizziness, nausea, gait difficulty and seizures.
8 ARIA-E: Includes radiographic ARIA-E and symptomatic ARIA-E.
9 ARIA-E is common in the indicated population and very common in the homozygote population.
10 Includes infusion related reaction and infusion site reaction.
In Study 301, symptomatic ARIA occurred in 2% (16/757) patients on lecanemab who are non-carriers and heterozygotes. Serious symptoms associated with ARIA that required hospitalisation were reported in 0.4% (3/757) of patients on lecanemab. Clinical symptoms associated with ARIA resolved in 75% (12/16) of patients during the period of observation.
Including asymptomatic radiographic events, ARIA was observed in 17% (128/757) of patients on lecanemab compared to 7% (55/764) patients on placebo in Study 301.
In Study 301, ARIA-E was observed in 9% (67/757) of patients on lecanemab compared with 1% (10/764) of patients on placebo. The majority of ARIA-E was asymptomatic, with symptomatic ARIA-E reported in 2% (12/757) of patients on lecanemab and no patients on placebo. When present, reported symptoms associated with ARIA-E included headache (50%, 6/12), confusion (17%, 2/12), dizziness (8%, 1/12) and nausea (8%, 1/12). Focal neurologic deficits (8%, 1/12) also occurred.
ARIA-H was observed in 13% (98/757) of patients on lecanemab compared with 7% (52/764) of patients on placebo. The majority of ARIA-H was asymptomatic, with symptomatic ARIA-H reported in 0.8% (6/757) of patients on lecanemab and 0.1% (1/764) of patients on placebo. ARIA-H and ARIA-E can occur together. There was no increase in isolated ARIA-H (i.e. ARIA-H in patients who did not also experience ARIA-E) for lecanemab compared to placebo.
The majority of ARIA-E radiographic events occurred early in treatment (within the first 7 doses), although ARIA-E can occur at any time and patients can have more than 1 episode. The maximum radiographic severity of ARIA-E in patients on lecanemab was mild in 4% (31/757), moderate in 4% (33/757), and severe in 0.3% (2/757) of patients. Resolution on MRI occurred in 64% (43/67) of patients by 12 weeks, 87% (58/67) by 17 weeks, and 100% (67/67) overall after detection, compared with 80% (8/10) of patients on placebo.
The maximum radiographic severity of ARIA-H microhaemorrhage in patients on lecanemab was mild in 8% (60/757), moderate in 1% (8/757), and severe in 1% (10/757) of patients; ARIA-H superficial siderosis was mild in 3% (26/757), moderate in 0.5% (4/757), and severe in 0.3% (2/757) of patients. See Table 1 in section 4.4 for MRI radiographic severity.
ARIA-E was observed in 9% (67/757) of patients on lecanemab, of which 88% (59/67) continued on lecanemab treatment with or without dose interruption. Among those that continued lecanemab, 14% (8/59) experienced a recurrence of ARIA-E.
ARIA-H (with or without concurrent ARIA-E) was observed in 13% (98/757) of patients on lecanemab and 7% (52/764) of patients on placebo, of which 80% (78/98) and 77% (40/52) continued treatment with or without dose interruption, respectively. Among those that continued, 36% (28/78) of patients on lecanemab and 30% (23/40) of patients on placebo experienced a recurrence of ARIA-H.
Isolated ARIA-H was observed in 8% (61/757) of patients on lecanemab and 6% (45/764) of patients on placebo, of which 97% (59/61) and 100% (45/45) continued treatment respectively with or without dose interruption. Among those that continued, 20% (12/59) of patients on lecanemab and 20% (10/45) of patients on placebo experienced a recurrence of ARIA-H.
The incidence of intracerebral haemorrhage was 0.3% (1/286) of patients on lecanemab with a concomitant antithrombotic medication at the time of the event compared to 0.7% (3/450) of patients who did not. Patients taking lecanemab with an anticoagulant alone or combined with an antiplatelet medication or aspirin had an incidence of intracerebral haemorrhage of 1.5% (1/68 patients) compared to no patients on placebo.
Approximately 15% of Alzheimer’s disease patients are ApoE ε4 homozygote carriers. In Study 301, the incidence of ARIA was lower in non-carriers (13% lecanemab vs 4% placebo) and heterozygotes (19% lecanemab vs 9% placebo) than in homozygotes (45% lecanemab vs 22% placebo). Among patients on lecanemab, ARIA-E occurred in 5% of non-carriers and 11% of heterozygotes compared with 33% of homozygotes. Symptomatic ARIA-E occurred in 1% of non-carriers and 2% of heterozygotes compared with 9% of homozygotes. ARIA-H occurred in 12% of non-carriers and 14% of heterozygotes compared with 38% of homozygotes. Symptomatic ARIA-H occurred in 1% of non-carriers and heterozygotes compared with 4% of homozygotes. Serious events of ARIA occurred in approximately 1% of non-carriers and heterozygotes carriers and 3% of homozygotes.
The recommendations on management of ARIA do not differ between ApoE ε4 carriers and non-carriers.
Infusion-related reactions were observed in Study 301 in 26% (237/898) patients treated with lecanemab and 75% (178/237) occurred with the first infusion. Infusion-related reactions were mostly mild (69%) or moderate (28%) in severity, severe infusion-related reactions were reported in less than 1% patients. Serious infusion-related reactions have also occurred. Infusion-related reactions resulted in discontinuations in 1% (12/898) patients on lecanemab. Symptoms of infusion-related reactions include fever and flu-like symptoms (chills, generalized aches, feeling shaky, and joint pain), nausea, vomiting, hypotension, hypertension and oxygen desaturation). Over 63% of patients who initially experienced infusion-related reactions had no further reactions with preventative medications (see section 4.4). The incidence of infusion-related reactions was similar regardless of ApoE ε4 genotype.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
Not applicable.
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