ENTRY 02 OF 07 · ACCELERATED APPROVAL

Leqembi, accelerated approval

Approved Leqembi (lecanemab) · case BUILT

Sponsor
Eisai Inc. Approval letter, p. 1
Action date
Approval letter, p. 11
Basis
Reduction in amyloid beta plaques Prescribing information (label), p. 2
Committee
Not referred to an advisory committee Approval letter, p. 3
Confirmatory
PMR 4384-1: randomized, controlled trialTrial completion 09/2022

What the sponsor asked the agency to accept

As the FDA restates it.

The applicant is seeking accelerated approval based on reduction in amyloid plaque burden measured by positron emission tomography (PET) imaging which is proposed to be reasonably likely to predict clinical benefit.

Summary review · PDF p. 3 · action of · fda.gov ↗

What the agency said

T1 · SurrogateConsistent

LEQ-T1-1

The Agency has previously found with the accelerated approval of aducanumab that reduction of brain Aβ plaque on PET is reasonably likely to predict clinical benefit in Alzheimer’s disease.

Summary review · PDF p. 4 · action of · fda.gov ↗

Compared to ADU-T1-1, Aduhelm, accelerated approval, .

T1 · SurrogateConsistent

LEQ-T1-2

There is substantial evidence that lecanemab reduces Aβ plaques, and this reduction is reasonably likely to result in clinical benefit for patients.

Summary review · PDF p. 5 · action of · fda.gov ↗

Compared to ADU-T1-2, Aduhelm, accelerated approval, .

T2 · Effect sizeConditional

LEQ-T2-1

Prespecified analyses of data at Week 79 suggested reduced decline on clinical endpoints by approximately 20% to 40%, as well as a reduced decline on other clinically meaningful outcome measures.

Summary review · PDF p. 28 · action of · fda.gov ↗

Compared to ADU-T2-1, Aduhelm, accelerated approval, .

T3 · ARIAConsistent

LEQ-T3-1

Risk of ARIA, including symptomatic ARIA, was increased in apolipoprotein E ε4 homozygotes compared to heterozygotes and noncarriers.

Prescribing information (label) · PDF p. 1 · action of · fda.gov ↗

Compared to ADU-T3-1, Aduhelm, accelerated approval, .

T3 · ARIAConsistent

LEQ-T3-2

Obtain an MRI prior to the 5th, 7th, and 14th infusions.

Prescribing information (label) · PDF p. 2 · action of · fda.gov ↗

Compared to ADU-T3-2, Aduhelm, accelerated approval, .

T3 · ARIADeparts

LEQ-T3-3

Consider testing for ApoE ε4 status to inform the risk of developing ARIA when deciding to initiate treatment with LEQEMBI.

Prescribing information (label) · PDF p. 5 · action of · fda.gov ↗

Compared to ADU-T3-1, Aduhelm, accelerated approval, .

T4 · DataConsistent

LEQ-T4-1

Given the robust, persuasive, and consistent effects of lecanemab on an acceptable surrogate endpoint, brain Aβ plaque on PET, Study 201 can be considered a single adequate and well-controlled trial that provides substantial evidence of effectiveness.

Summary review · PDF p. 5 · action of · fda.gov ↗

Compared to ADU-T4-2, Aduhelm, accelerated approval, .

T4 · DataConditional

LEQ-T4-2

Although the 6- month exposure numbers did not meet the ICH E1 guideline, the Division considers that the number of 1 year exposures and the determination that Alzheimer’s disease is a serious and life-threatening disease offset those limitations.

Summary review · PDF p. 5 · action of · fda.gov ↗

Compared to ADU-T4-3, Aduhelm, accelerated approval, .

T5 · ConfirmatoryConsistent

LEQ-T5-1

In order to verify the clinical benefit of lecanemab-irmb, conduct a randomized, controlled trial to evaluate the efficacy of lecanemab-irmb compared to an appropriate control for the treatment of Alzheimer’s disease.

Approval letter · PDF p. 3 · action of · fda.gov ↗

Compared to ADU-T5-1, Aduhelm, accelerated approval, .

Advisory committee

Your application for Leqembi was not referred to an FDA advisory committee because this biologic did not raise new or unexpected safety or efficacy issues for a drug of this class.

Approval letter · PDF p. 3 · action of · fda.gov ↗