Leqembi

HOS-100319 · has-adverse-reaction-information · PDF-Seite 8

Summary of the safety profile The safety of lecanemab has been evaluated in 2203 patients who received at least one dose of lecanemab. 8 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. 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 Adverse reaction Frequency category (SOC) Immune system Hypersensitivity reactions1 Common disorders Delayed hypersensitivity reactions2,3 Common Nervous system Headache Very Common disorders ARIA4 Very Common ARIA-H5,6 Very Common

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HOS-100315 · has-contraindication-information · PDF-Seite 4

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).

HOS-100314 · has-indication-information · PDF-Seite 2

Leqembi is indicated for the treatment of adult patients with a clinical diagnosis of mild cognitive impairment and mild dementia due to Alzheimer’s disease (Early Alzheimer’s disease) who are apolipoprotein E ε4 (ApoE ε4) non-carriers or heterozygotes with confirmed amyloid pathology (see section 4.4).

HOS-100317 · has-interaction-information · PDF-Seite 8

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).

HOS-100318 · has-pregnancy-information · PDF-Seite 8

Women of childbearing potential 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. Pregnancy 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. Breast-feeding 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. Fertility There are no data on the effects of lecanemab on human fertility.

HOS-100316 · has-warning-information · PDF-Seite 4

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. 4 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. 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). 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. 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). 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 treatmen

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