Possible Consequences of the Approval of a Disease-Modifying Therapy for Alzheimer Disease

Abstract

On July 8, 2020, Biogen submitted an application to the US Food and Drug Administration (FDA) for approval of aducanumab for the treatment of Alzheimer disease (AD) dementia. Aducanumab, a monoclonal antibody targeting aggregated amyloid-β, showed in a phase 3 clinical trial (but apparently not in another phase 3 trial) success in clearing amyloid plaques from the brain and slowing the rate of cognitive decline in some patients with mild AD dementia. 1 While the aducanumab clinical trial data are complicated and the path to approval far from clear, approval is certainly possible, and other promising antibodies (such as Biogen's BAN-2401 and Genentech's gantenerumab) are just steps behind. Thus, the long-awaited advent of disease-modifying therapy for AD may be soon upon us, representing a major advance in the battle against AD and a beacon of muchneeded hope for patients. However, the potential seismic effect of a disease-modifying therapy for AD requires serious consideration because it could present significant challenges for AD clinical practice and research, some of which are considered here.

Associations between thinner retinal neuronal layers and suboptimal brain structural integrity: Are the eyes a window to the brain?

“…Diffuse cortical atrophy occurs in normal ageing but is more pronounced in AD, beginning in the medial temporal lobes in preclinical AD and gradually progressing throughout the brain (Eckerström et al, 2018; Kulason et al, 2020; Pini et al, 2016). The neuropathological changes of AD begin more than a decade prior to the onset of clinical symptoms, (Sperling et al, 2014) and existing treatments for AD may be most effective in the earliest stages of the disease (Musiek and Morris, 2021). Thus, biomarkers that can identify people with preclinical AD or at high risk of developing AD, and that are able to be widely implemented for population screening, are imperative to initiating treatments at the optimal stage, preserving quality of life.…”

Practical Considerations in the Administration of Aducanumab for the Neurologist

“…The capacity of academic memory disorder centers to absorb this demand may be stretched as indicated by a recent analysis. 28 Similarly, the increased demands on diagnostic Aβ PET imaging and MRI-based surveillance monitoring may further burden imaging facilities. 29 For private practices entering into the world of infusible therapies for the first time, consideration of how insurers reimburse infusible therapies, which infusion sites are covered under a patient's insurance benefit, and familiarizing themselves with infusion billing codes are critical.…”

Aducanumab and disease modifying treatments for Alzheimer's disease

“…In a recent consultation exercise by the Royal College of Psychiatrists, commissioned by Alzheimer's Research UK, 16 only 36% of psychiatrists thought their services could adapt to deliver DMTs. Additionally, the likely restrictive criteria for its use in patients with very early AD, would create a difficult task for clinicians having to explain to patients with more progressive AD who have eagerly waited for DMTs to be approved that they cannot access this medication 17 …”