Biogen Pulls Plug on Controversial Alzheimer Disease Drug Aduhelm

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Aduhelm (aducanumab-avwa) was granted accelerated approval by the FDA in June 2021 despite misgivings from the agency's Peripheral and Central Nervous System Drugs Advisory Committee.

Image credit: Artur | stock.adobe.com

Image credit: Artur | stock.adobe.com

Biogen Inc. has announced it will discontinue the development and commercialization of its controversial Alzheimer disease (AD) treatment Aduhelm (aducanumab-avwa).1 The monoclonal antibody was granted accelerated approval by the FDA in June 2021 as a first-of-its kind therapy for AD, a disease that had not seen a significant approval since 2003.2

The discontinuation—which Biogen stated was not related to safety or efficacy concerns—will allow the company, along with partner Eisai, to focus on advancing Leqembi (lecanemab-irmb), the first anti-amyloid beta treatment for AD to be granted traditional approval by the FDA.3

“As a pioneer in Alzheimer’s disease, Biogen is reprioritizing resources to build a leading franchise to address the multiple pathologies of the disease and patient needs. We plan to further advance the launch of Leqembi, together with Eisai, and continue to bolster innovation with the development of the other assets in our pipeline,” Biogen President and CEO Christopher A. Viehbacher said in a press release. “When searching for new medicines, one breakthrough can be the foundation that triggers future medicines to be developed. Aduhelm was that groundbreaking discovery that paved the way for a new class of drugs and reinvigorated investments in the field.”1

The accelerated approval of Aduhelm was based on a pair of Phase III clinical trials, EMERGE (NCT02484547) and ENGAGE (NCT02477800). Both trials enrolled patients with mild cognitive impairment due to AD or mild AD dementia with confirmed brain amyloid by positron emission tomography scan. Both of the trials were halted in 2019 after reaching a predefined futility endpoint related to the effect on cognitive decline, despite consistent evidence showing a decrease in amyloid-β plaques in the brain.4

Analysis of the findings indicated improvements in cognitive decline in the high-dose group in EMERGE with uncertain clinical relevance; however, the ENGAGE study did not reach a similar finding.4

In November 2020, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee voted against recommending the approval of Aduhelm.4 The final vote as to whether findings from the EMERGE trial were sufficient as primary evidence for the efficacy of Aduhelm was 10-0 (10 no, 0 yes, 1 uncertain) that the trial did not provide such evidence. The committee voted 8-1 (8 no, 1 yes, 2 uncertain) that the trial showed efficacy in patients with mild AD and voted 7–0 (7 no, 0 yes, 4 uncertain) that findings from the Phase I PRIME trial (NCT01677572) demonstrated supporting evidence of efficacy.5

However, the FDA still granted the accelerated approval, raising the ire of many stakeholders across the healthcare landscape who questioned the benefit-risk profile for Aduhelm. In clinical trials, approximately one-third of patients showed evidence of localized brain edema and/or hemorrhage. Most patients were asymptomatic, however, many developed symptoms that required discontinuation or holding of Aduhelm.4

“The FDA’s decision to approve [Aduhelm] for anyone with Alzheimer’s disease, regardless of severity, showed a stunning disregard for science, eviscerated the agency’s standards for approving new drugs, and ranks as one of the most irresponsible and egregious decisions in the history of the agency,” Michael Carome, MD, of Public Citizen’s Health Research Group, wrote in a letter to US Department of Health & Human Services Secretary Xavier Becerra.6

Health systems such as the Cleveland Clinic and Mount Sinai Health System decided not to offer the treatment until additional evidence of clinical benefits was shown.7 In April 2022, CMS issued a national coverage determination that stated it will not broadly cover Aduhelm unless adequate evidence was presented demonstrating sufficient efficacy and safety to warrant traditional FDA approval.8 Then in May 2022, Biogen’s CEO and most of its Aduhelm commercial marketing team stepped down, after less than $6 million in sales following the drug’s approval.9,10

“After January 2023, Biogen began a strategic review of its research and development efforts, including seeking potential partners or external financing for Aduhelm, as part of a focus on prioritizing the company’s portfolio,” the company wrote in a news release. “During this process, Biogen considered the time and investment required for the post-marketing confirmatory ENVISION study and the likely advancements in the field by the time of potential Aduhelm FDA traditional approval. Despite an extensive process, the company did not identify potential strategic partners or external financing.”1

Biogen announced a one-time charge of approximately $60 million in closeout costs for the Aduhelm program in the fourth quarter of 2023 and the rights to the drug have now reverted to Neurimmune.

“We have gained significant insight from the development of Aduhelm and will carry this forward as we continue our pioneering work in Alzheimer’s disease,” Biogen Head of Development Priya Singhal, MD, MPH, said in a press release.1

References

1. 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

2. FDA Grants Accelerated Approval for Alzheimer’s Drug. News release. FDA. June 7, 2021. Accessed January 31, 2024. https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-alzheimers-drug

3. FDA converts novel Alzheimer’s disease treatment to traditional approval. FDA. July 6, 2023. Accessed January 31, 2024. https://www.fda.gov/news-events/press-announcements/fda-converts-novel-alzheimers-disease-treatment-traditional-approval

4. Aduhelm. Alzforum. Updated August 18, 2021. Accessed January 31, 2024. https://www.alzforum.org/therapeutics/aduhelm

5. FDA. Peripheral and Central Nervous System Drugs Advisory Committee Meeting. November 6, 2020. Accessed January 31, 2024.

6. Carome MA. RE: the FDA’s reckless decision to approve aducanumab for treating Alzheimer’s disease. Public Citizen. June 16, 2021. Accessed January 31, 2024. https://www.citizen.org/wp-content/uploads/2590.pdf

7. Belluck P. Cleveland Clinic and Mount Sinai won’t administer Aduhelm to patients. New York Times. July 14, 2021. Accessed January 31, 2024. https://www.nytimes.com/2021/07/14/health/cleveland-clinic-aduhelm.html

8. CMS finalizes Medicare coverage policy for monoclonal antibodies directed against amyloid for the treatment of Alzheimer’s disease. Center for Medicare & Medicaid Services. 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

9. Robbins R. Biogen C.E.O. will step down after disastrous launch of Alzheimer’s drug. The New York Times. May 3, 2022. Accessed January 31, 2024. https://www.nytimes.com/2022/05/03/business/biogen-aduhelm-michel-vounatsos.html

10. Liu A. Biogen sends CEO to the exit, abandons Aduhelm sales team in $1B overhaul. Fierce Pharma. May 3, 2022. Accessed January 31, 2024. https://www.fiercepharma.com/pharma/biogen-ceo-steps-down-amid-aduhelm-fallout-biotech-trims-commercialteam-1b-cost-cutting

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