Alzheimer Disease
Loren Bonner
The controversial drug aducanumab (Aduhelm—Biogen) continues to make news headlines almost a year after FDA approved it to treat patients with mild cognitive impairment or mild stage Alzheimer disease.
Because of uncertainty over the medication’s safety and efficacy, CMS announced in January 2022 that health insurance coverage for aducanumab will only be granted under special circumstances; Medicare will cover aducanumab for participants of clinical trials approved by CMS. Although many agree with the approach, CMS has fielded nearly 10,000 public comments criticizing the proposal and said a final decision on Medicare coverage of aducanumab is expected in April 2022.
“On one hand, I completely understand the idea that coverage should require evidence development and that there is a need to collect and study the data in a comprehensive manner to evaluate its clinical benefits,” said Marketa Marvanova, PharmD, PhD, BCGP, BCPP, dean and professor at the University of Montana Skaggs School of Pharmacy.
“On the other hand, I think that the degree of the proposed coverage is very restrictive and will significantly impede access to this therapy,” Marvanova said. Those who live in rural areas or far away from large urban research medical centers would not have the same access, for instance.
Aducanumab is a high-cost medication with known risks of amyloid-related imaging abnormalities (ARIA) due to brain inflammation, which can be caused from fluid retention, brain edema, and microhemorrhages.
Administration and continued therapy of the drug requires regular amyloid PET and MRI imaging as well as access to expert clinicians trained in recognizing mild cognitive impairment and early Alzheimer disease, with knowledge of genetic counseling and testing, too.
Todd Semla, PharmD, BCGP, FCCP, a clinical associate professor at Northwestern University’s Feinberg School of Medicine, said he hopes there are randomized controlled trials that can detect cognitive and functional outcomes as well as changes in betaamyloid levels.
“I hope that patients covered and enrolled in the trials are widely available in order to recruit a diverse study population that represents the spectrum of all peoples afflicted by [Alzheimer disease],” he said.
What is aducanumab?
Aducanumab is an immunoglobulin gamma 1 monoclonal antibody directed against soluble and insoluble forms of beta-amyloid, lowering levels of brain beta-amyloid observable on PET brain imaging.
Aducanumab, as the first representative of the medication class of monoclonal antibodies directed against beta-amyloid, addresses the underlying pathophysiology of Alzheimer disease and is the first disease-modifying therapy.
Aducanumab’s approval
Beta-amyloid plaque is considered a biomarker of Alzheimer disease in the brain, but Marvanova said it remains unclear whether a reduction of it provides any meaningful clinical benefits. Aducanumab reduces beta-amyloid plaques.
“This approval was made by FDA without convincing evidence of benefits and with known harms of ARIA,” said Marvanova.
Aducanumab is only approved for use in individuals with mild cognitive impairment or mild dementia due to Alzheimer disease with evidence of beta-amyloid pathology.
“It is also important to stress that, at the moment, treatment with aducanumab is not warranted for individuals with moderate or advanced [Alzheimer disease] dementia, other dementia, or for those without evidence of beta-amyloid plaques in the brain,” she said.
Knowledge gaps
“It is important for pharmacists, like other health care professionals involved in pharmacotherapy for older adults, to be prepared to educate patients and family about aducanumab,” said Semla, who authored a new commentary in JAMA Network Open recognizing and addressing the public’s knowledge gaps concerning aducanumab and Alzheimer disease. “To do so, they will need a basic understanding of aducanumab’s history, controversial approval by FDA, and current availability.”
Like any drug, pharmacists must know about aducanumab’s safety profile, efficacy, dose, preparation, and monitoring requirements. Pharmacists working closely with patients seeking to receive aducanumab will need to understand eligibility criteria for clinical trials approved by CMS or insurance prior authorization criteria if seeking payment outside of CMS.
There are many sources for this information, including aducanumab’s label, Biogen, FDA, and professional societies such as the American Geriatrics Society, the Alzheimer’s Association, and the American Academy of Neurology (AAN). AAN recently issued a new “evidence-in-focus” report published in Neurology, where authors reviewed data from 4 aducanumab studies and concluded: “Whether aducanumab will result in a clinically meaningful slowing of [Alzheimer disease] symptoms remains to be determined, as does the safety of aducanumab in clinical
populations.”
“It is important to discuss with the patient and families that aducanumab is not a cure for [Alzheimer disease] and there is currently insufficient evidence on its efficacy for cognition and function and for [Alzheimer disease] progression,” said Marvanova. ■