LEQEMBI Concentrate for solution for infusion Ref.[115156] Active ingredients: Lecanemab

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).

ApoE4 Testing

ApoE4 genotype should be assessed by a CE-marked in vitro diagnostic (IVD) with the corresponding intended purpose. If the CE-marked IVD is not available, an alternative validated test should be used (see section 5.1).

Testing for ApoE ε4 status should be performed prior to initiation of treatment with lecanemab to inform the risk of developing ARIA (see sections 4.1 and 5.1). 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 5^th, 7^th and 14^th infusions. If a patient experiences symptoms suggestive of ARIA at any time during treatment, clinical evaluation should be performed including an MRI (see section 4.4).

Recommendations for Dosing Interruptions or Treatment Discontinuation in Patients with ARIA

ARIA-E

Dosing may continue in asymptomatic, mild radiographic ARIA-E cases. Suspend dosing for any symptomatic or radiographically moderate or severe ARIA-E. A follow-up MRI to assess for resolution 2 to 4 months after initial identification should be performed. Once the MRI demonstrates radiographic resolution and symptoms, if present, resolve, resumption of dosing should be guided by clinical judgment. See Table 1 for MRI radiographic severity (see section 4.4).

Use clinical judgment in considering whether to continue dosing in patients with recurrent ARIA-E. After the second occurrence of symptomatic or radiographically moderate or severe ARIA-E, treatment with lecanemab should be discontinued (see section 4.8).

ARIA-H

Dosing may continue in asymptomatic, mild radiographic ARIA-H cases. Suspend dosing for any symptomatic mild or moderate or radiographically moderate ARIA-H. A follow-up MRI to assess for stabilisation 2 to 4 months after initial identification should be performed. Once the MRI demonstrates radiographic stabilisation and symptoms, if present, resolve, resumption of dosing should be guided by clinical judgement (see section 4.8). In the event of radiographically or symptomatic severe ARIA-H, treatment with lecanemab should be permanently discontinued. See Table 1 for MRI radiographic severity (see section 4.4).

Intracerebral Haemorrhage

Lecanemab should be permanently discontinued if intracerebral haemorrhage greater than 1 cm in diameter occurs.

Delayed or missed doses

If an infusion is missed, the next dose should be administered as soon as possible.

Special populations

Elderly

No dose adjustment is necessary in patients ≥65 years (see section 5.1).

Renal impairment

No specific dose adjustment is necessary in patients with mild to moderate renal impairment (see section 5.2).

Hepatic impairment

No specific dose adjustment is needed for patients with mild to moderate hepatic impairment (see section 5.2).

Paediatric population

There is no relevant use of lecanemab in the paediatric population.

Method of administration

Lecanemab is for intravenous use only. Lecanemab is administered as an intravenous infusion over approximately 1 hour once every 2 weeks. For the first infusion, the patient should be observed for approximately 2.5 hours following completion of the infusion for signs and symptoms of infusion related reactions (see section 4.4).

Lecanemab is diluted prior to intravenous infusion.

For instructions on dilution of the medicinal product before administration, see section 6.6.

There is limited clinical experience with lecanemab overdose.

Unopened vial: 2 years.

After preparation of the infusion solution.

Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C. From a microbiological point of view, unless the method of dilution precludes the risks of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.

Store in a refrigerator (2°C – 8°C).

Store in the original package in order to protect from light.

Do not freeze or shake vials.

For storage conditions after dilution of the medicinal product, see section 6.3.

2 mL of concentrate containing 200 mg lecanemab in a 6 mL vial (Type I clear glass), with a stopper (chlorobutyl) and a seal (aluminium) with a dark grey flip-off cap, in a pack size of 1.

5mL of concentrate containing 500 mg lecanemab in a 6 mL vial (Type I clear glass), with a stopper (chlorobutyl) and a seal (aluminium) with a white flip-off cap, in a pack size of 1.

Each carton contains one vial.

Not all pack sizes may be marketed.

Parenteral medicinal products should be inspected visually for particulate matter and discolouration prior to administration. In the event of either being observed, discard the medicinal product.

Preparation of infusion solution

Calculate the dose, the total volume of lecanemab solution required, and the number of vials needed based on the patient’s actual body weight. Each vial contains a lecanemab concentration of 100 mg/mL.

Withdraw the required volume of lecanemab from the vial(s) and add to 250 mL 0.9% sodium chloride solution for injection.

Gently invert the infusion bag containing the lecanemab diluted solution to mix completely. Do not shake.

Infusion bags manufactured using polypropylene, polyvinyl chloride, co-extruded polyolefin/polyamide, or ethylene/propylene copolymer have been confirmed to be compatible for administration of lecanemab.

After dilution, immediate use is recommended.

Administration of infusion solution

Prior to infusion, allow the lecanemab diluted solution to warm to room temperature.

Infuse the entire volume of lecanemab intravenously over approximately 1 hour through an intravenous line containing a terminal low-protein binding 0.2 micron in-line filter (compatible filter materials include polytetrafluoroethylene, polyethersulfone, polycarbonate, polyvinylidenedifluoride, polypropylene, polyurethane and polysulfone). Flush infusion line to ensure all lecanemab is administered.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.