Rolling Submission for Subcutaneous Lecanemab

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Eisai and Biogen announced they have initiated a rolling submission for the subcutaneous (SC) version of the Alzheimer disease (AD) therapy lecanemab-irmb (US brand name: Leqembi®) for weekly maintenance dosing. Leqembi is indicated for the treatment of AD in patients with mild cognitive impairment or mild dementia stage of disease. The newly initiated rolling submission is backed by data from the phase III Clarity AD study.¹

The FDA’s fast-track designation for the approved intravenous (IV) Leqembi did not extend to the new SC formulation, pushing back plans. The rolling submission, originally scheduled for March, was delayed after the FDA requested additional 3-month immunogenicity data on the SC formulation proposed maintenance dose of 360 mg weekly.²

Back in March, Eisai admitted that only 2000 patients in the United States were undergoing treatment with Leqembi, far below the target of 10,000 by the end of 2023.³ This may be in part due to the difficulties surrounding IV administration of Leqembi. If approved by the FDA, the Leqembi SC autoinjector could be used to more easily administer the treatment at home or at medical facilities. First, it shortens administration time, as the injection process is not as lengthy as the IV formulation. Second, it would reduce the need for hospital visits and care following administration as compared with the IV formulation. Lastly, the SC maintenance dosing may be more convenient for both patients and caregivers. After the discontinuation of aducanumab (Aduhelm) in January 2024, could this be the distinction that sets Leqembi apart?⁴

As part of the regimen under review, patients who completed the biweekly IV initiation phase would receive weekly doses that maintain effective drug concentrations of Leqembi. This would sustain the clearance of protofibrils, considered to be the most toxic form of Aβ plaque, which can cause continued neuronal injury even after the Aβ plaque has been removed.¹

Leqembi has had a long, complicated journey since its breakthrough therapy designation back in July 2021 and full FDA approval in July 2023. While Leqembi has been generally better received than aducanumab, it has struggled to achieve market success.^4,5 

Following aducanumab’s discontinuation, Biogen switched efforts to focus on Leqembi with partners Eisai, and other treatment modalities in the pipeline, including BIIB080 and BIIB113. “When searching for new medicines, one breakthrough can be the foundation that triggers future medicines to be developed," said Biogen CEO Chris Viehbacher at that time.⁴ "Aduhelm was that groundbreaking discovery that paved the way for a new class of drugs and reinvigorated investments in the field.”

References

1. Eisai initiates rolling Biologics License Application to US FDA for LEQEMBI® (lecanemab-irmb) for subcutaneous maintenance dosing for the treatment of early Alzheimer’s disease under the fast track status. News release. May 14, 2024. Accessed May 15, 2024. https://investors.biogen.com/news-releases/news-release-details/eisai-initiates-rolling-biologics-license-application-us-fda

2. O’Brien E. FDA: specific fast track designation for subcutaneous formulation of Leqembi for Alzheimer disease needed for rolling review. Psychiatric Times. April 3, 2024. https://www.psychiatrictimes.com/view/fda-specific-fast-track-designation-for-subcutaneous-formulation-of-leqembi-for-alzheimer-disease-needed-for-rolling-review

3. Kamat P. Eisai, Biogen finally kick off FDA submission for subcutaneous Leqembi. First Word Pharma. May 14, 2024. Accessed May 15, 2024. https://firstwordpharma.com/story/5856737

4. Kuntz L. Biogen discontinues aducanumab for Alzheimer disease. Psychiatric Times. January 31, 2024. https://www.psychiatrictimes.com/view/biogen-discontinues-aducanumab-for-alzheimer-disease

5. Kuntz L. Moving forward: Alzheimer treatment granted breakthrough therapy designation. Psychiatric Times. July 30, 2021. https://www.psychiatrictimes.com/view/moving-forward-alzheimer-treatment-granted-breakthrough-therapy-designation