Aducanumab (AduhelmTM) – the first disease-modifying treatment for Alzheimer’s disease approved by the US Food and Drug Administration, 7 June 2021

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Availability of Aduhelm remains unclear

Coverage by Medicare and other third-party payers unknown

More information to follow

R. Scott Turner, PhD, MD, and the Memory Disorders Program

On June 6th we celebrated the 77th anniversary of D-Day. Today, June 7th, will likely become known as D-Day in the war against Alzheimer’s disease (AD). The day we stormed the beaches – with the first disease-modifying treatment for dementia due to AD. This analogy implies there is still much to do, and no guarantee of success, but perhaps this advance truly marks the beginning of the end.

Despite conflicting evidence of effectiveness, with one phase 3 trial positive and a parallel trial negative, and unfavorable opinions by outside reviewers, the FDA approved aducanumab (AduhelmTM) for the treatment of dementia due to AD. However, a post-approval phase 4 trial must be conducted by the sponsors (Biogen and Eisai) to confirm effectiveness. Aduhelm thus joins more than 100 monoclonal antibodies already FDA-approved – targeting cancers, autoimmune/inflammatory diseases, and infectious diseases including COVD-19. Aduhelm is the first and only drug approved for AD to reduce the accumulation of amyloid plaques in the brain – a core underlying pathology of the disease. Antibody treatment reduced amyloid plaques by 59-71% at 18 months of treatment.

Treatment with an anti-amyloid monoclonal antibody is only effective if amyloid accumulation is confirmed in the brain – either by brain imaging (an amyloid PET scan), or analysis of cerebrospinal fluid or blood (plasma) proteins (amyloid and tau). The antibody must be given intravenously over 1 hour, monthly, for years, requiring either outpatient or visiting home-nurse infusions. Aduhelm treatment is recommended in addition to conventional oral drugs for the treatment of AD (donepezil, rivastigmine, galantamine, and memantine). Aduhelm is not approved for other dementing disorders, individuals with mild cognitive impairment, or for healthy older individuals at-risk (the worried well). Expectations must be tempered – effectiveness translates into a significantly slower rate of cognitive and functional decline (compared to those treated with placebo) – but this is real progress – a foot in the door.

The major side effects of Aduhelm are swelling (termed ARIA-E for edema) and microhemorrhages (ARIA-H for hemorrhage) of the brain. While these side effects, if they occur, are usually asymptomatic (detectable by brain MRI only) and temporary, they may cause new symptoms including headache and worsened confusion in up to 24% of treated individuals, and warrant either temporary or permanent discontinuation of treatment. These symptoms usually occur as the antibody dose is ramped up – within the first several months of treatment.

The timeline for availability of Aduhelm in pharmacies remains unclear. Third-party coverage – for diagnostic testing as well as treatment – also remains to be determined. We will recommend and prescribe Aduhelm as indicated – and as it becomes available and covered by third-party payers. Additional implications, including modification of ongoing and planned studies of AD – will follow. The EMBARK study of aducanumab, however, will continue as planned and will provide additional information on safety and effectiveness.

The Memory Disorders Program, Department of Neurology, MedStar Georgetown University Hospital, is proud and honored to have made significant contributions to this and other advances in AD treatment and prevention. We thank our many colleagues at Georgetown and elsewhere who contributed to this milestone event. We especially thank the many altruistic and courageous patients – and their study partners – who joined us in clinical research, including the studies leading to Aduhelm approval.