The promise and questions of Aducanumab

On June 7, 2021, the US Food & Drug Administration (FDA) announced its accelerated approval of a new drug, aducanumab (brand name: Aduhelm), to treat Alzheimer’s disease — the first approval of its kind since 2003. Naturally, employers and health plans have questions about what this means for the treatment landscape, costs and patient outcomes.

Alzheimer’s disease treatment landscape

Alzheimer’s disease takes a terrible toll on patients, families and the health system. It is the most common type of dementia, accounting for two-thirds of all cases of dementia; it is characterized by amyloid plaques and neurofibrillary tangles in the brain. In the United States, where it is the sixth leading cause of death, a person develops Alzheimer’s disease nearly every minute.¹,²,³ The incidence of the disease increases with age, doubling every five years after people turn 65. It is estimated that 15 million Americans will have Alzheimer’s disease by 2060.⁴

At first glance, it would appear that the FDA’s decision on aducanumab represents new hope for Alzheimer’s patients and their families. It is the first drug to focus on modifying disease progression rather than treating symptoms. Manufactured by Biogen/Eisai, the drug works to clear beta amyloid proteins from the brain and was intended for patients with mild cognitive impairment and in the early stages of Alzheimer’s dementia.

Despite aducanumab’s promise to slow the rate of cognitive and functional decline, that outcome is unclear after several clinical trials. The FDA granted aducanumab accelerated approval based on amyloid plaque removal as a surrogate for slowing disease progression. Final approval depends on an additional large clinical trial demonstrating that removing beta amyloid plaques has cognitive benefits. This accelerated approval was despite the FDA’s own Advisory Committee recommendation against approval, with multiple members of the committee resigning in protest of the approval.⁵ The manufacturer has 72 months — six years — to provide that proof. In the meanwhile, patients can be treated with aducanumab, even though there are many lingering questions and concerns about the drug — concerns about safety, efficacy and cost.

Safety

As the Institute for Clinical Effectiveness Research (ICER) has noted, the “side effects [of Aduhelm] are both common and potentially serious.”⁶ As the manufacturer itself has noted on the label, adverse reactions include ARIA-E (edema, or brain swelling) and ARIA-H (microhemorrhage, or brain bleeding).⁷ In two placebo-controlled studies, 35 percent of patients experienced brain swelling and 19 percent experienced brain bleeding.

Practically speaking, these adverse reactions can cause higher rates of falls, as well as confusion, disorientation, gait disturbance, visual disturbance/blurred vision, headache and nausea. To monitor the potential development of brain swelling and/or bleeding, patients receiving aducanumab will require an MRI to establish a baseline and ongoing scans to manage drug dosing, which will add to the overall cost of care.

Efficacy

The effectiveness of aducanumab is in question. The manufacturer had two trials with discordant results — one met its primary endpoint, the other did not.⁸ Surprisingly, the FDA in its approval did not restrict the patient population in which the drug can be used, even though trials were conducted only with patients with mild cognitive impairment and mild Alzheimer’s dementia.⁹ Therefore, the FDA label allows the drug to be prescribed for any person living with Alzheimer’s disease.¹⁰

Cost

With a cost of $56,000 per year, aducanumab is priced at seven times the amount recommended by ICER.¹¹,¹² There will be additional costs for patients, public and private plan sponsors for initial assessment and ongoing monitoring with lab testing and advanced imaging. Because the incidence of disease is much higher in people over age 70, aducanumab is unlikely to have a large cost impact on the commercially insured; our modeling shows an estimate of $0.21 to $1.04 PMPM for employers and $0.27 to $1.41 for health plans.

Access

As ICER notes, many Medicare beneficiaries may have to pay more than $10,000 in out-of-pocket costs annually under Part B. In a statement, the Alzheimer’s Association, while applauding the FDA’s decision to approve aducanumab, also said, “This price is simply unacceptable. For many, this price will pose an insurmountable barrier to access; it complicates and jeopardizes sustainable access to this treatment and may further deepen issues of health equity.”¹³

CVS Caremark Initial Approach

Given these considerations, CVS Caremark will have coverage criteria that will ensure patients have clinically appropriate access to aducanumab. Criteria will focus on ensuring patients who are initiated on aducanumab will have necessary baseline cognitive assessments and diagnostic testing to establish diagnosis. Given the safety concerns about the drug, criteria will require ongoing review of appropriate documentation and imaging. Criteria will ensure prescribing is done by or in consultation with clinicians with dementia expertise. All available data and information will be reviewed by our Pharmacy and Therapeutics Committee, which bases its decisions on scientific evidence, standards of practice, medical literature, clinical guidelines and other appropriate information.

This is the first new therapy for Alzheimer’s disease in many years. The FDA’s accelerated approval of aducanumab has brought both excitement and concern to patients, caregivers, providers, employers and health plans. As with all drug approvals, our team is actively evaluating the label and diagnostic information for aducanumab, as well as any safety guidance from the FDA to determine coverage decisions.