The world of Alzheimer disease (AD) in the United States has been fraught with controversy since Biogen’s aducanumab (Aduhelm) received FDA approval to enter the US market as the first treatment to directly target AD pathology. (1) Prior to aducanumab, existing treatments only addressed the symptoms of AD. These treatments reduced the speed of AD progression by months to a year, and had no impact on AD pathogenesis.
Aducanumab is an amyloid-ß-directed monoclonal antibody, shown to reduce amyloid-ß plaques in positron emission tomography (PET) imaging studies. (2) The drug’s controversy begins with the FDA’s approval: Biogen was granted accelerated approval, which is reserved for serious or life-threatening illnesses that provide a tangible therapeutic advantage over existing treatment. (3)
To qualify for FDA-accelerated approval, the drug has to first demonstrate potential to address an unmet medical need to treat a serious condition. Second, the drug has to improve a surrogate endpoint that is likely to produce a clinical benefit to patients. Therefore, in being the first drug to directly address AD pathology by reducing amyloid plaque volume, it satisfied the requirements of accelerated approval. (3)
Since the FDA did not require clinical benefit data for approval to market, Biogen was able to start selling aducanumab as early as June 7, 2021. In order to retain FDA market approval, Biogen stakeholders hope that post-market trials will demonstrate clinical benefit, ie, reduction in AD burden and improvement in quality-of-life measures.
The controversy surrounding aducanumab consists of two components. First, the FDA allows a drug to enter the US market prior to demonstrating any improvement in patient condition, all the while exposing patients to neurological risks such as brain swelling and microhemorrhages. (3)
Second, the drug is expensive: the $56,000 per year price tag plus periodic PET imaging studies required to monitor for efficacy and adverse events have the potential to financially cripple the Centers for Medicare and Medicaid Services (CMS). (3) Additionally, current post-market approval trials have yet to verify aducanumab’s expected clinical benefit, mirroring underwhelming results in Biogen’s pre market trials.(4)
Until physicians are presented with substantive evidence of benefit, they would rather a family use that money towards prevention, early detection, and patient support like home health services.(4) These actions mitigate the impact of the disease on people living with AD and their caregivers, thereby improving quality-of-life. In the meantime, Americans are hopeful that a breakthrough in AD treatment is on the horizon.
This article has been approved and reviewed by the Scientific Writing Team Lead of ESURGI: Ishtiak Ahmed Chowdhury
- FDA News Release. (2021, July 7). FDA Grants Accelerated Approval for Alzheimer’s Drug. US Food & Drug Administration. https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-alzheimers-drug
- Biogen Inc. (2021, June). Aduhelm: Highlights of prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761178s000lbl.pdf
- Young, K.D. (16 July 2021). No Net Benefit of Aducanumab for Alzheimer’s Disease, Expert Panel Results. Medscape Medical News. https”//www.medscape.com/viewarticle/954909
Shaw, G. (2021, July 12). FDA Narrows Aduhelm Label. Pharmacy Practice News. https://www.pharmacypracticenews.com/Online-First/Article/03-16/FDA-Narrows-Aduhelm-Label/64066