Earlier this year in June, the U.S. Food and Drug Administration (FDA) approved a new Alzheimer disease (AD) drug for the first time since 2003.¹ Biogen’s Aduhelm (aducanumab) is a monoclonal antibody infusion that’s administered every 4 weeks and targets amyloid beta plaque aggregates in the brain – an underlying cause of AD.^2,3 Aduhelm is currently labeled only for treatment of AD patients with mild cognitive impairment or mild dementia (the patient population studied in clinical trials).⁴ It’s notindicated for patients with more severe disease or other types of dementia since these patients weren’t studied and there’s no safety or efficacy data available.^3,4

FDA Approval

Aduhelm’s approval was viewed by many as controversial. It was approved by the FDA via the Accelerated Approval pathway.^1,2 This pathway is intended to provide earlier access to drugs for serious or life-threatening illnesses when a new drug is reasonably likely to provide a clinical benefit (over existing therapies), but when there is still some uncertainty about the new drug.²

You can learn more about the controversy surrounding Aduhelm here and more about Accelerated Approval and the FDA’s decision to approve Aduhelm here.

Considerations

The approval of a new AD drug is certainly exciting, but the extent of this drug’s practical clinical benefit is unknown. The trials used to study Aduhelm are conflicting and it’s unclear how (or if) the data translates to a clinically meaningful effect.^1-3 The drug is also not benign; reported adverse effects include brain swelling, microhemorrhages, headaches, falls, diarrhea, and confusion^.3-5 Last, but definitely not least, the major drawback is the cost and impact on healthcare spending…The annual cost for the drug alone is listed as $56,000 per patient! Additional expenses to consider include the potential cost of tests / scans to confirm the presence of amyloid beta – not all patients diagnosed with AD will have elevated amyloid levels (not currently required by FDA labeling) and the definite costs of at least three brain scans per patient to monitor for swelling and microhemorrhages (required by FDA labeling).^3-6 Some payers have already said that Aduhelm won’t be a covered treatment option.³

Impact on Medicare

Aduhelm utilization would have an incredible impact on Medicare spending since most AD patients are Medicare beneficiaries.⁶ The indefinite monthly infusion would fall under Medicare Part B, as an outpatient physician-administered therapy.^6,7 Approximately 6 million Americans have AD and if even 10% of these patients receive the drug, the overall Medicare Part B spending could nearly double from around $37 billion per year to $69 billion per year.⁶ Not to be forgotten is the potential financial impact on Medicare beneficiaries themselves; the estimated out-of-pocket coinsurance cost is up to $11,000 per year for just the medication.⁷ The Centers for Medicare & Medicaid Services (CMS) have yet to determine their stance on Aduhelm coverage.^6,7

Bottom Line

Aduhelm’s place in therapy is unclear at this time. The evidence is conflicting and it’s uncertain how the trial data translates to the broader AD patient population. One review found that the clinical trials used to support Aduhelm’s approval would have excluded more than 92% of Medicare beneficiaries with AD based on age and comorbidities.⁸ It is unknown to what extent prescribers will adopt this treatment considering the extreme potential costs to AD patients and society as a whole (via Medicare) – not to mention potentially severe consequences of use like brain swelling and microhemorrhages. Nonetheless, this is one drug to keep an eye on because of its potential impact on national healthcare spending.

Written By:

John Corrigan, PharmD

Clinical Pharmacist, OnePoint Patient Care

References:

1. Cavazzoni P. FDA’s Decision to Approve New Treatment for Alzheimer’s Disease. U.S. Food and Drug Administration. June 7, 2021. Accessed August 18, 2021. https://www.fda.gov/drugs/news-events-human-drugs/fdas-decision-approve-new-treatment-alzheimers-disease
2. Dunn B, Stein P, Cavazonni P. Approval of Aducanumab for Alzheimer disease the FDA’s Perspective. JAMA Intern Med. Published online July 13, 2021. doi:1001/jamainternmed.2021.4607
3. Educate Why Aduhelm Isn’t a Miracle for Alzheimer’s. Pharmacist’s Letter. August 2021. Accessed August 18, 2021. https://pharmacist.therapeuticresearch.com/Content/Articles/PL/2021/Aug/Educate-Why-Aduhelm-Isn-t-a-Miracle-for-Alzheimer-s
4. Package Insert. Biogen. 2021. Accessed September 13, 2021. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=41706573-546f-6774-6872-5374726f6e67
5. Rabinovich G. Controversy and Progress in Alzheimer’s Disease – FDA Approval of Aducanumab. N Engl J Med. 2021;(9):771-774. doi:1056/NEJMp2111320
6. Schulman K, Greicius M, Barak R. Will CMS Find Aducanumab Reasonable and Necessary for Alzheimer Disease After FDA Approval? JAMA. 2021;326(5):383-384. doi:1001/jama.2021.11768
7. Crosson F, Covinsky K, Redberg F. Medicare and the Shocking US Food and Drug Administration Approval of Aducanumab. JAMA Intern Med. Published online July 13, 2021.      doi:1001/jamainternmed.2021.4610
8. Anderson T, Ayanian J, Souza J, Landon B. Representativeness of Participants Eligible to Be Enrolled in Clinical Trials of Aducanumab for Alzheimer Disease Compared with Medicare Beneficiaries With Alzheimer Disease and Mild Cognitive Impairment. JAMA. Published online September 9, 2021. doi:1001/jama.2021.15286