Leqembi

Treatment should be initiated and supervised by physicians experienced in the diagnosis and treatment of Alzheimer’s disease with timely access to Magnetic Resonance Imaging (MRI). Lecanemab infusions should be administered by qualified healthcare professionals trained to monitor for, recognize and manage infusion-related reactions.

Patients treated with lecanemab must be given the patient card and be informed about the risks of lecanemab (see also package leaflet). 3 ApoE4 Testing ApoE4 genotype should be assessed by a CE-marked in vitro diagnostic (IVD) with the corresponding intended purpose.

1). 1). Prior to testing patients should be appropriately counselled and consented according to national or local guidelines, as applicable. Posology The recommended dose of lecanemab is 10 mg/kg body weight administered as an intravenous (IV) infusion once every 2 weeks.

Treatment with lecanemab should be discontinued once the patient progresses to moderate Alzheimer’s disease. During treatment with lecanemab, cognitive function testing and clinical symptom assessment should occur approximately every 6 months.

The cognitive testing and symptom progression should be used to assess whether the patient has progressed to moderate Alzheimer's dementia, and/or if the clinical course otherwise suggests that lecanemab has not demonstrated effectiveness in the patient, and inform the decision as to whether treatment with lecanemab should be discontinued.

Monitoring for Amyloid Related Imaging Abnormalities (ARIA) Lecanemab can cause ARIA, characterized as ARIA with oedema (ARIA-E), which can be observed on MRI as brain oedema or sulcal effusions, and ARIA with haemosiderin deposition (ARIA-H), which includes microhaemorrhage and superficial siderosis.

In addition to ARIA, intracerebral haemorrhages greater than 1 cm in diameter have occurred in patients treated with lecanemab. Obtain a recent (within 6 months) baseline brain MRI prior to initiating treatment with lecanemab to evaluate for pre-existing ARIA.

Obtain an MRI prior to the 3rd, 5th, 7th and 14th infusions. In general, the MRI should be performed within approximately one week before the scheduled infusion of lecanemab and reviewed prior to proceeding with the infusion. 4). Recommendations for Dosing Interruptions or Treatment Discontinuation in Patients with ARIA ARIA-E Dosing may continue in asymptomatic, mild radiographic ARIA-E cases.

Summary of the safety profile 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 9 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%). 1% (1/764) patients on placebo. Fatal events of intracerebral haemorrhage in patients receiving lecanemab have been observed.

Tabulated list of adverse reactions 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.

Controlled access programme and registry 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.

5 Traceability 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 Hypersensitivity reactions, including angioedema, bronchospasm, and anaphylaxis, have occurred in patients who were treated with lecanemab which may be serious.

2). Amyloid beta pathology The presence of amyloid beta pathology must be confirmed via an appropriate test prior to initiating treatment. Amyloid Related Imaging Abnormalities (ARIA) 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, 1/3 experienced recurrent ARIA.

8). 8). 8). In addition to ARIA, intracerebral haemorrhages greater than 1 cm in diameter have occurred in patients treated with lecanemab. 8). Monitoring for ARIA 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.

2). Radiographic Findings The radiographic severity of ARIA associated with lecanemab was classified by the criteria shown in Table 1. 6 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.

1. Patients with bleeding disorders that are not under adequate control. 4). 4).