The company will discontinue the development and commercialization of aducanumab-avwa (Aduhelm) for intravenous use and will terminate the ENVISION clinical study.
Biogen announced plans to reprioritize resources for their Alzheimer disease (AD) franchise, continuing to advance lecanemab-irmb (Leqembi) and accelerating the antisense oligonucleotide targeting tau BIIB080 as well as an oral small molecule inhibitor of tau aggregation, BIIB113, according to a press release from the company. The company will also discontinue the development and commercialization of aducanumab-avwa (Aduhelm) 100 mg/mL injection for intravenous use and will terminate the ENVISION clinical study, with the decision not relating to safety or efficacy concerns.1
BillionPhotos.com - stock.adobe.com
A large proportion of the resources regarding aducanumab will be reallocated in the AD franchise, the company press release said.1
“As a pioneer in [AD], 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 [lecanemab], together with Eisai, and continue to bolster innovation with the development of the other assets in our pipeline,” Christopher A. Viehbacher, president and CEO of Biogen, said in the press release. “When searching for new medicines, one breakthrough can be the foundation that triggers future medicines to be developed. [Aducanumab] was that groundbreaking discovery that paved the way for a new class of drugs and reinvigorated investments in the field.”1
In January 2023, the company reviewed its research and development efforts, which included potential partners and external financing for aducanumab. Through the process, Biogen evaluated the time and investment required in the post-marketing confirmatory ENVISION study along with the likely advancement to the disease by the time of the potential approval of aducanumab by the FDA. The company was unable to identify potential strategic partners or external financing, according to the press release.1
3 Key Takeaways
Biogen Inc has announced a strategic shift in its Alzheimer's disease (AD) franchise, focusing on advancing lecanemab-irmb (Leqembi), BIIB080 (antisense oligonucleotide targeting tau), and BIIB113 (oral small molecule inhibitor of tau aggregation),
Aducanumab's approval in 2021 faced criticism, with concerns about its approval standards and safety. The decision was viewed by some as an erosion of minimum standards for drug approval related to evidence of efficacy and safety.
Public Citizen expressed a "greater concern" about lecanemab, citing evidence that its clinical benefits do not outweigh substantial health risks. The drug has a black box warning for brain swelling and bleeding risks.
The company recorded a one-time charge of approximately $60 million due to the close-out costs for the program in the fourth quarter of 2023, and terminated the license acquired for aducanumab from Neurimmune. The right to the drug will be reverted back to Neurimmune.1
Aducanumab has been heavily criticized. Following the approval of aducanumab in 2021, Curtis E Haas, PharmD, FCCP, editor-in-chief for Pharmacy Practice in Focus: Health Systems® called the FDA’s approval of aducanumab a “further erosion of the minimum standards for drug approval related to evidence of efficacy and safety.”2
In the EMERGE and ENGAGE phase 3 clinical trials, the trials were stopped early because they reached the predefined futility endpoint relative to the effects on cognitive decline, Haas said in the article. However, a reanalysis the data suggested improvements in cognitive decline in the EMERGE trial, but there was clinical relevance uncertainty. The ENGAGE study lacked those similar findings. Initially, the drug was approved with no limitations even with the lack of available data for early stages of disease, according to Haas. The approval was amended to limit the indication for mild stages of the disease, although criticism ensued regarding the FDA approval process, questioning the credibility of the review.2
In 2021, Public Citizen expressed their outrage over the approval of aducanumab, stating it was “one of the most irresponsible and egregious decisions in the history of the agency.” They cited that the drug lacked clinically meaningful benefits and had a risk of potentially serious brain injury, according to a statement.3
With the approval of lecanemab, the future of the disease state seems promising. However, according to an article on Pharmacy Times, its use is limited due to the restricted indication, safety risk, and limited patient access.4 Lecanemab does include a black box warning regarding amyloid-related imaging abnormalities as well as warnings and precautions related to infusion-related reactions and hypersensitivity reactions, according to the authors.4
However, Public Citizen has also addressed the focus of lecanemab as a “greater concern” than aducanumab.3
“Of greater concern is lecanemab (Leqembi), Biogen’s second drug for Alzheimer’s disease, and another FDA failure. In 2023, lecanemab received full approval, despite the evidence that the drug’s clinical benefits did not outweigh its substantial health risks. The prescribing information for lecanemab includes a black box warning for brain swelling and bleeding risks. Although patients with [AD] and their families are desperate for better treatments, neither aducanumab, and now lecanemab, are the answer,” Robert Steinbrook, MD, director of Health Research Group of Public Citizen, said in the Public Citizen statement.3
Eisai serves as lead of lecanemab development and regulatory submissions will be facilitated by both Eisai and Biogen commercializing and co-promoting the drug. Eisai will have the final decision-making authority, according to the press release. BIIB080 is licensed from Ionis.1
Biogen to realign resources for Alzheimer’s disease franchise. News release. Biogen. January 31, 2024. Accessed February 1, 2024. https://investors.biogen.com/news-releases/news-release-details/biogen-realign-resources-alzheimers-disease-franchise
Haas CE. Aducanumab may indicate erosion of drug approval standards. Pharmacy Times. September 1, 2021. Accessed February 1, 2024. https://www.pharmacytimes.com/view/aducanumab-may-indicate-erosion-of-drug-approval-standards
Alzheimer’s drug lecanemab (Lequembi) of greater concern than little-used aducanumab. News release. Public Citizen. February 1, 2024. Accessed February 1, 2024. https://www.citizen.org/news/alzheimers-drug-lecanemab-leqembi-of-greater-concern-than-little-used-aducanumab/
Ryabo D, Khan I, Amirov A, Shahin M, Zerilli T. Clinical overview: lecanemab offers hope for patients with Alzheimer disease. Pharmacy Times. October 17, 2023. Accessed February 1, 2024. https://www.pharmacytimes.com/view/clinical-overview-lecanemab-offers-hope-for-patients-with-alzheimer-disease