Leqembi Adverse Reactions

Summary of the safety profile: The safety of lecanemab has been evaluated in 2,203 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.
Tabulated list of adverse reactions: The following adverse reactions listed in Table 3 as follows 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. (See Table 3.)

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Description of selected adverse reactions: Incidence of ARIA in the Indicated Population: 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 2 in Precautions for MRI radiographic severity.
Recurrence of ARIA in the Indicated Population: 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.
Intracerebral Haemorrhage in the Indicated Population: 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.
ApoE ε4 Carrier Status and Risk of ARIA: Approximately 15% of Alzheime'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: 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 Precautions). The incidence of infusion-related reactions was similar regardless of ApoE e4 genotype.
Reporting of suspected adverse reactions: 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.