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.
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 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 the table 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.
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.
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. The incidence of infusion-related reactions was similar regardless of ApoE ε4 genotype.
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