Biogen Abandons Aducanumab, Pivots Focus to Lecanemab for Alzheimer Disease

After a controversial accelerated FDA approval¹ and a tumultuous time in the marketplace, Biogen is discontinuing development and commercialization of aducanumab-avwa (Aduhelm), the first anti–amyloid beta treatment approved for Alzheimer disease.²

Aducanumab (Aduhelm) was initially approved under the accelerated pathway in 2021.

Image credit: SpeedShutter - stock.adobe.com

Instead, Biogen will pivot to put more focus on lecanemab-irmb (Leqembi), another Alzheimer drug that received accelerated approval January 6, 2023,³ and full, traditional approval on July 6, 2023,⁴ after a confirmatory trial verified the therapy’s clinical benefit. Lecanemab is approved to treat early Alzheimer disease, or mild cognitive impairment or dementia.

Biogen said it is ending the ENVISION clinical study for aducanumab, a postmarketing study with the goal of gaining full approval from the FDA. According to the company, it was unable to identify potential partners or external financing for aducanumab. In addition, the company analyzed the time and investment for the postmarketing study and how much the field was likely to advance by the time the results were available for a traditional approval.²

As a result of the decision to discontinue commercialization of aducanumab, Biogen will pay a one-time charge of approximately $60 million to Neurimmune, from which Biogen had licensed aducanumab. The rights to aducanumab revert back to Neurimmune.²

After aducanumab was granted accelerated approval on June 7, 2021, the FDA’s decision was met with intense scrutiny and backlash.⁵ At the center of the controversy was the question of whether the decision was ethical.

The monoclonal antibody was the first new drug approval for Alzheimer disease in nearly 2 decades, but there was little evidence proving that reduction of amyloid helped patients improve memory and cognitive problems, but trials showed the drug could cause brain swelling or bleeding.¹ Two previous trials of aducanumab were halted when data showed patients received no benefit to their cognitive function. An analysis of another trial found aducanumab resulted in slightly slower cognitive declines at higher doses.⁶

The FDA ultimately approved aducanumab despite the advisory committee overwhelmingly rejecting the drug after reviewing the clinical trial data. While the FDA usually follows the recommendations of its advisory committees, it does not have to. After the FDA announced the approval, 3 of the scientists on the committee that advised against approval resigned.⁷

In addition to the controversial approval, aducanumab received a price tag of $56,000 annually.⁸ By December 2021, Biogen had reduced the cost to $28,000 annually.⁹ Between the high price tag and the fraught approval decision, CMS released a national Coverage Determination (NCD) to limit coverage of Alzheimer disease biologics that target plaque build-up in the brain, such as aducanumab, to patients who were enrolled in certain clinical trials.¹⁰

When lecanemab received its accelerated approval 19 months after aducanumab, the NCD automatically applied to it, even though the data was more promising. The phase 3 confirmatory CLARITY AD trial found lecanemab successfully reduced cognitive and functional decline by 27% at 18 months compared with placebo.¹¹

After lecanemab received full approval, CMS confirmed it would offer broader Medicare coverage.¹² Eisai and Biogen listed lecanemab at $26,500 a year, less than either of aducanumab’s price tags, but still well above estimates that the drug would achieve cost-effectiveness thresholds if priced between $8900 and $21,500 annually.¹³

Another Alzheimer disease drug may soon receive approval. While the FDA declined to grant accelerated approval¹⁴ to donanemab for early symptomatic Alzheimer disease, Eli Lilly subsequently submitted the drug to the FDA for full approval.¹⁵

References

1. Melillo G. How Biogen’s Aduhelm approval marks a precipitous turning point for the FDA. The American Journal of Managed Care. July 14, 2021. Accessed January 31, 2024. https://www.ajmc.com/view/how-biogen-s-aduhelm-approval-marks-a-precipitous-turning-point-for-the-fda

2. Biogen to realign resources for Alzheimer’s disease franchise. Biogen. News release. January 31, 2024. Accessed January 31, 2024. https://investors.biogen.com/news-releases/news-release-details/biogen-realign-resources-alzheimers-disease-franchise

3. Joszt L. FDA approves lecanemab to treat early Alzheimer disease. The American Journal of Managed Care. January 6, 2023. Accessed January 31, 2024. https://www.ajmc.com/view/fda-approves-lecanemab-to-treat-early-alzheimer-disease

4. Joszt L. FDA grants full approval for Alzheimer drug lecanemab. The American Journal of Managed Care. July 6, 2023. Accessed January 31, 2024. https://www.ajmc.com/view/fda-grants-full-approval-for-alzheimer-drug-lecanemab

5. Belluck P, Kaplan S, Robbins R. How an unproven Alzheimer’s drug got approved. New York Times. July 19, 2021. Updated October 20, 2021. Accessed January 31, 2024. https://www.nytimes.com/2021/07/19/health/alzheimers-drug-aduhelm-fda.html

6. Biogen plans regulatory filing for aducanumab in Alzheimer’s disease based on new analysis of larger dataset from phase 3 studies. News release. Biogen. October 22, 2019. Accessed January 31, 2024. https://investors.biogen.com/news-releases/news-release-details/biogen-plans-regulatory-filing-aducanumab-alzheimers-disease

7. Belluck P, Robbins R. Three F.D.A. advisers resign over agency’s approval of Alzheimer’s drug. New York Times. June 10, 2021. Updated September 21, 2021. Accessed January 31, 2024. https://www.nytimes.com/2021/06/10/health/aduhelm-fda-resign-alzheimers.html

8. Biogen and Eisai launch multiple initiatives to help patients with Alzheimer’s disease access Aduhelm. News release. Biogen. June 7, 2021. Accessed January 31, 2024. https://investors.biogen.com/news-releases/news-release-details/biogen-and-eisai-launch-multiple-initiatives-help-patients

9. Biogen announces reduced price for Aduhelm to improve access for patients with early Alzheimer’s disease. News release. Biogen. December 20, 2021. Accessed January 31, 2024. https://investors.biogen.com/news-releases/news-release-details/biogen-announces-reduced-price-aduhelmr-improve-access-patients

10. CMS finalizes Medcare coverage policy for monoclinal antibodies directed against amyloid for the treatment of Alzheimer’s disease. News release. CMS. April 7, 2022. Accessed January 31, 2024. https://www.cms.gov/newsroom/press-releases/cms-finalizes-medicare-coverage-policy-monoclonal-antibodies-directed-against-amyloid-treatment

11. Joszt L. Alzheimer disease drug lecanemab successfully reduces cognitive, functional decline. The American Journal of Managed Care. September 29, 2022. Accessed January 31, 2024. https://www.ajmc.com/view/alzheimer-disease-drug-lecanemab-successfully-reduces-cognitive-functional-decline

12. Statement: broader Medicare coverage of Leqembi available following FDA traditional approval. News release. CMS. July 6, 2023. Accessed January 31, 2024. https://www.cms.gov/newsroom/press-releases/statement-broader-medicare-coverage-leqembi-available-following-fda-traditional-approval

13. Alzheimer’s disease: an assessment of lecanemab. Institute for Clinical and Economic Review. March 17, 2023. Accessed January 31, 2024. https://icer.org/assessment/alzheimers-disease-2022

14. FDA declines to give accelerated approval to donanemab in early symptomatic Alzheimer disease. The American Journal of Managed Care. January 20, 2023. Accessed January 31, 2024. https://www.ajmc.com/view/fda-declines-to-give-accelerated-approval-of-donanemab-in-early-symptomatic-alzheimer-disease

15. Myshko D. FDA decision on donanemab for Alzheimer’s expected by end of year. Formulary Watch. July 17, 2023. Accessed January 31, 2024. https://www.formularywatch.com/view/fda-decision-on-donanemab-for-alzheimer-s-expected-by-end-of-year