Drug Update · Neurology

lecanemab and donanemab: amyloid confirmation and PET criteria for patient selection

July 20, 2026

LEQEMBI starting dose

10 mg/kg every 2 weeks (IV) [9][11]

LEQEMBI maintenance options

10 mg/kg IV every 4 weeks or 360 mg SC once weekly (after 18 months) [9][11]

KISUNLA infusion schedule

Infusion 1: 350 mg; Infusion 2: 700 mg; Infusion 3: 1,050 mg; Infusion 4+: 1,400 mg every 4 weeks [8]

Imaging monitoring (LEQEMBI)

Baseline MRI and MRI prior to 3rd, 5th, 7th, and 14th infusions [9]

Imaging monitoring (KISUNLA)

Baseline MRI and MRI prior to 2nd, 3rd, 4th, and 7th infusions; amyloid PET cited for stopping decisions [8]

Clinical Perspective

Clinicians (neurologists, geriatricians, and memory‑clinic teams) should ensure documented amyloid pathology before initiating either lecanemab or donanemab, and perform baseline brain MRI as required by each label ^[2]^[1]. The labels support use of serial MRI during early dosing and, for donanemab specifically, consideration of amyloid PET to inform stopping decisions when plaque levels reach minimal thresholds ^[1]^[2]^[4]. What remains to be defined is the practical operational workflow in clinic for amyloid confirmation and PET‑guided stopping: which patients should get PET versus other amyloid confirmation methods, and how local PET availability will affect treatment pathways?

Dr. Vikram Patel · Neurology

Leqembi (lecanemab‑irmb) and Kisunla (donanemab‑azbt) labels require confirmation of amyloid beta pathology before initiating therapy in patients with mild cognitive impairment or mild dementia due to Alzheimer’s disease ^[2]^[1]. Both labels mandate baseline brain MRI and schedule serial MRIs during early dosing; the donanemab label explicitly cites amyloid PET as a basis for considering treatment discontinuation after plaque reduction ^[1]^[2].

Clinical Context

Both lecanemab and donanemab are monoclonal antibodies directed at aggregated forms of amyloid beta and are indicated for the treatment of Alzheimer’s disease initiated in the mild cognitive impairment or mild dementia stage, the populations studied in pivotal trials ^[2]^[1]^[4]. The US prescribing information for lecanemab notes that clinical trials used amyloid PET to quantify plaque burden; the donanemab label references amyloid PET thresholds for treatment decisions ^[4]^[1]. Both manufacturers include amyloid confirmation and MRI monitoring in their dosing and monitoring guidance ^[2]^[1]. The labels also highlight increased risk of amyloid‑related imaging abnormalities in ApoE ε4 homozygotes and recommend consideration of ApoE ε4 testing before starting therapy ^[2]^[1].

Key Findings

Patient selection: Both LEQEMBI and KISUNLA prescribing information state: confirm the presence of amyloid beta pathology prior to initiating treatment ^[2]^[1]. Imaging and monitoring: LEQEMBI recommends obtaining a recent baseline brain MRI prior to initiating treatment and an MRI within approximately one week prior to the 3rd, 5th, 7th, and 14th infusions ^[2]. KISUNLA recommends a baseline MRI and MRI prior to the 2nd, 3rd, 4th, and 7th infusions, and it provides explicit dosing interruption guidance tied to ARIA radiographic severity ^[1]. Amyloid PET in trials and labels: LEQEMBI clinical studies included an amyloid PET substudy to measure reductions in plaque burden, and KISUNLA labeling states that clinicians can consider stopping dosing based on reduction of amyloid plaques to minimal levels on amyloid PET imaging ^[4]^[1]. Regulatory context: the FDA converted lecanemab’s accelerated approval to traditional approval following verification of clinical benefit in Study 301 (CLARITY AD) ^[3].

Safety & Tolerability

Amyloid related imaging abnormalities (ARIA), including ARIA‑E (edema/effusion) and ARIA‑H (hemosiderin deposition), are named in both labels ^[2]^[1].
Infusion‑related reactions are listed for LEQEMBI and KISUNLA ^[2]^[1].
Headache is listed among the most common adverse reactions for LEQEMBI and KISUNLA ^[2]^[1].
ARIA‑H manifestations explicitly named in the KISUNLA label include microhemorrhage and superficial siderosis ^[1].

Study Design

Leqembi (lecanemab‑irmb) efficacy was evaluated in randomized controlled trials including Study 301 (CLARITY AD); the FDA converted lecanemab to traditional approval after a confirmatory trial verified clinical benefit ^[3]^[4]. In LEQEMBI clinical programs, amyloid PET was used in substudy analyses to quantify plaque reduction ^[4]. Kisunla (donanemab‑azbt) prescribing information describes dosing and monitoring guidance tied to radiographic ARIA severity and references amyloid PET for plaque measurement and potential treatment discontinuation ^[1]. Where numeric trial endpoints are reported in the labels or FDA summaries they should be consulted directly in the referenced prescribing information ^[3]^[4].

FAQ

What is LEQEMBI (lecanemab) and KISUNLA (donanemab) approved for?

LEQEMBI (lecanemab‑irmb) is indicated for the treatment of Alzheimer’s disease and, per prescribing information, treatment should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the populations studied in clinical trials. KISUNLA (donanemab‑azbt) is indicated for the treatment of Alzheimer’s disease and the highlights specify initiation in patients with mild cognitive impairment or mild dementia stage of disease.

How do these drugs work?

Both LEQEMBI and KISUNLA are monoclonal antibodies directed against aggregated forms of amyloid beta. The lecanemab label describes it as an amyloid beta‑directed antibody that reduces amyloid beta plaques; donanemab similarly targets aggregated amyloid beta with guidance tied to plaque measurement in imaging.

What are the recommended doses and imaging/monitoring requirements?

LEQEMBI recommended starting dosage is 10 mg/kg administered every 2 weeks by intravenous infusion; after 18 months clinicians may continue every 2 weeks or transition to maintenance dosing (intravenous 10 mg/kg every 4 weeks or subcutaneous 360 mg once weekly) according to prescribing information. LEQEMBI recommends a recent baseline brain MRI prior to initiating therapy and an MRI within approximately one week prior to the 3rd, 5th, 7th, and 14th infusions. KISUNLA dosing is described as an intravenous infusion series with Infusion 1: 350 mg; Infusion 2: 700 mg; Infusion 3: 1,050 mg; Infusion 4 and beyond: 1,400 mg administered every four weeks; baseline MRI is required with additional MRIs prior to the 2nd, 3rd, 4th, and 7th infusions. Clinicians should consult current prescribing information for complete dosing guidance.

What are the most common side effects clinicians should counsel patients about?

Both labels list amyloid related imaging abnormalities (ARIA) — ARIA‑E and ARIA‑H — as a key risk and recommend MRI monitoring; ApoE ε4 homozygotes have higher incidence of ARIA and testing is suggested prior to initiation to inform risk discussion. Infusion‑related reactions and headache are also listed among common adverse reactions in the prescribing information for both agents, and KISUNLA additionally names ARIA‑H manifestations including microhemorrhage and superficial siderosis.

Clinicians should consult current prescribing information for complete dosing guidance.

lecanemab and donanemab: amyloid confirmation and PET criteria for patient selection

lecanemab and donanemab: amyloid confirmation and PET criteria for patient selection

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

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