FDA Extends Review for Eisai/Biogen's LEQEMBI IQLIK Starting-Dose Subcutaneous Regimen for Early Alzheimer's Disease; PDUFA Date Set to August 24, 2026.

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Eisai Co., Ltd. and Biogen Inc. said the U.S. Food and Drug Administration (FDA) has extended the review period by three months for a supplemental Biologics License Application (sBLA) for a once-weekly lecanemab-irmb subcutaneous injection (U.S. brand name: LEQEMBI IQLIK) as a starting dose for the treatment of early Alzheimer’s disease. The new Prescription Drug User Fee Act (PDUFA) action date is August 24, 2026.

The FDA requested additional information as part of the ongoing review process and determined the submission constituted a major amendment to the sBLA, extending the PDUFA date to allow time for a full review of the additional materials. The companies said the FDA has not raised concerns to date regarding the approvability of LEQEMBI IQLIK as a starting dose.

Regulatory timeline and context

Eisai and Biogen said they believe the comprehensive clinical data package supporting subcutaneous administration of LEQEMBI across multiple studies and dosing regimens supports the potential use of LEQEMBI IQLIK for initiation therapy, following FDA approval of the subcutaneous maintenance dosing regimen on August 26, 2025.

The companies also noted that LEQEMBI has been approved by more than 50 regulatory authorities worldwide.

Indication

LEQEMBI is indicated for the treatment of Alzheimer’s disease. Treatment should be initiated in patients with mild cognitive impairment (MCI) or mild dementia stage of disease, consistent with the population in which treatment was initiated in clinical trials.

Key safety information (selected)

WARNING: Amyloid-Related Imaging Abnormalities (ARIA)

Monoclonal antibodies directed against aggregated forms of beta amyloid, including LEQEMBI, can cause ARIA, characterized as ARIA with edema (ARIA-E) and ARIA with hemosiderin deposition (ARIA-H). Incidence and timing vary among treatments. ARIA usually occurs early in treatment and is usually asymptomatic, but serious and life-threatening events, including seizure and status epilepticus, can occur. ARIA can be fatal. Serious intracerebral hemorrhages (ICH) >1 cm, including some fatal events, have been observed with this class of medications.
Because ARIA-E can cause focal neurologic deficits that can mimic an ischemic stroke, clinicians should consider whether symptoms could be due to ARIA-E before giving thrombolytic therapy.
ApoE ε4 homozygotes: Patients who are ApoE ε4 homozygotes (about 15% of patients with Alzheimer’s disease) have a higher incidence of ARIA, including symptomatic, serious, and severe radiographic ARIA, compared with heterozygotes and noncarriers. Testing for ApoE ε4 status should be performed prior to initiation to inform ARIA risk.

ARIA and ICH incidence (reported)

Symptomatic ARIA occurred in 3% and serious ARIA symptoms in 0.7% with LEQEMBI.
Clinical ARIA symptoms resolved in 79% of patients during the period of observation.
ARIA (including asymptomatic radiographic events) was observed: 21% with LEQEMBI vs 9% with placebo.
ARIA-E was observed: 13% with LEQEMBI vs 2% with placebo.
ARIA-H was observed: 17% with LEQEMBI vs 9% with placebo.
No increase in isolated ARIA-H was observed for LEQEMBI vs placebo.
ICH >1 cm in diameter was reported in 0.7% with LEQEMBI vs 0.1% with placebo, and fatal ICH events have been observed in patients taking LEQEMBI.

Risk factors highlighted in the prescribing information

ApoE ε4 carrier status: Among patients taking LEQEMBI, 16% were ApoE ε4 homozygotes, 53% were heterozygotes, and 31% were noncarriers. ARIA was higher in ApoE ε4 homozygotes (LEQEMBI: 45%; placebo: 22%) than in heterozygotes (LEQEMBI: 19%; placebo: 9%) and noncarriers (LEQEMBI: 13%; placebo: 4%). Symptomatic ARIA-E occurred in 9% of ApoE ε4 homozygotes vs 2% of heterozygotes and 1% of noncarriers. Serious ARIA events occurred in 3% of ApoE ε4 homozygotes and in ~1% of heterozygotes and noncarriers.
Radiographic findings suggestive of cerebral amyloid angiopathy (CAA): Baseline MRI findings such as at least 2 microhemorrhages or at least 1 area of superficial siderosis were identified as risk factors for ARIA. Patients were excluded from Clarity AD for the presence of >4 microhemorrhages and additional findings suggestive of CAA, including prior cerebral hemorrhage >1 cm in greatest diameter, superficial siderosis, vasogenic edema, or other lesions that could increase ICH risk.
Concomitant antithrombotic or thrombolytic medication: Antithrombotic medications did not increase the risk of ARIA with LEQEMBI. The incidence of ICH was 0.9% in patients taking LEQEMBI with a concomitant antithrombotic medication vs 0.6% with no antithrombotic, and 2.5% in patients taking LEQEMBI with an anticoagulant alone or with antiplatelet medication such as aspirin vs none in patients receiving placebo. Fatal cerebral hemorrhage has occurred in one patient taking an anti-amyloid monoclonal antibody in the setting of focal neurologic symptoms of ARIA and the use of a thrombolytic agent.

Monitoring and dose management

Baseline brain MRI and periodic MRI monitoring are recommended.
Enhanced clinical vigilance for ARIA is recommended during the first 14 weeks of treatment.
Clinical judgment should guide whether to continue dosing or temporarily or permanently discontinue based on ARIA-E/ARIA-H clinical symptoms and radiographic severity.

Infusion-related reactions and adverse reactions (selected)

Infusion-related reactions (IRRs) were observed: 26% with LEQEMBI vs 7% with placebo, with 75% of LEQEMBI cases occurring with the first infusion.
IRRs were mostly mild (69%) or moderate (28%). Reported symptoms included fever and flu-like symptoms (including chills, generalized aches, feeling shaky, and joint pain), nausea, vomiting, hypotension, hypertension, and oxygen desaturation.
The most common adverse reactions reported in ≥5% with LEQEMBI infusion every 2 weeks and ≥2% higher than placebo included IRRs (26% vs 7%), ARIA-H (14% vs 8%), ARIA-E (13% vs 2%), headache (11% vs 8%), superficial siderosis of the central nervous system (6% vs 3%), rash (6% vs 4%), and nausea/vomiting (6% vs 4%).
The safety profile of LEQEMBI IQLIK for maintenance treatment was reported as similar to LEQEMBI infusion, with localized and systemic (less frequent) injection-related reactions (mild to moderate in severity).

What Eisai and Biogen said

Eisai and Biogen said they look forward to ongoing discussions with the FDA as the review progresses and are committed to bringing the advancement to patients and care partners as quickly as possible, providing greater flexibility and choice in how anti-amyloid treatment is delivered.