This Tuesday, the Centers for Medicare and Medicaid Services (CMS) announced that Medicare coverage of aducanamab would be limited to clinical trial participants. Aducanamab, sold commercially by Biogen as Aduhelm, is a monoclonal antibody treatment for Alzheimer’s Disease that works by clearing amyloid beta, a protein involved in Alzheimer’s pathology, from the brain.

Prior to CMS’s announcement, the possibility of Medicare covering Aduhelm had already driven increased Medicare Part B premiums. These increased premiums were announced last November and went into effect at the start of this year. In December, Biogen announced that the price of Aduhelm would be reduced from $56,000 to $28,000 annually. U.S. Secretary of Health and Human Services Xavier Bercerra released a statement Monday advising CMS to adjust Medicare premiums to reflect the change in price.

Aduhelm’s troubled history

Aduhelm has long been plagued by controversy that goes beyond the treatment’s five-figure price tag and its effect on Medicare premiums. Trials of the drug were originally abandoned in 2019 due to a lack of promising results, but resumed after Biogen concluded that data from one of two trials demonstrated Aduhelm’s potential as an Alzheimer’s treatment.

In addition to this mixed data surrounding Aduhelm’s efficacy, the high incidence of side effects known as amyloid-related imaging abnormalities (ARIA) in trial participants for aduhelm and other immunotherapies meant to remove amyloid is cause for concern among scientists. ARIA can manifest as brain swelling or bleeding, and while the exact mechanism driving these phenomena has not been identified, it is thought to result from damage to the brain vasculature that occurs when the drug clears deposits of amyloid beta from these vessels.

The murky picture painted by this data led an advisory committee to the Food and Drug Administration (FDA) to recommend against approving Aduhelm in November 2020. The following January, the FDA delayed its decision date from March to June so that the drug could receive further review. The the FDA ultimately approved Aduhelm in their June decision.

The road ahead for Biogen

Even with FDA approval, Biogen’s troubles are far from over. The conditions under which Aduhelm was approved spurred Janet Woodcock, acting FDA commissioner, to call for an independent federal investigation into the FDA’s dealings with Biogen.

In addition to this ongoing investigation, the death of a 75-year-old patient after taking Aduhelm has amplified safety concerns surrounding the drug. Prior to her death, the patient had been hospitalized and diagnosed with brain swelling. While the link between Aduhelm and the patient’s death has not been definitively proven, news of this accident cast a shadow over Biogen’s presentation of final study data at last November’s Clinical Treatment for Alzheimer’s Disease conference.

New Aduhelm safety data shows that many of patients taking the drug develop brain swelling or bleeding, although Biogen maintains that most such cases are asymptomatic.

CMS’ decision to limit Medicare coverage of Aduhelm reflects broader concerns and skepticism regarding the drug. This preliminary decision will be followed in April with a final decision regarding Aduhelm coverage.