The incidence of brain swelling was highest in the group of patients who received the highest doses of Aduhelm, as well as the group of patients who are carriers of the APoE gene.
A new study found that 41% of patients who received a high dose of Biogen’s controversial Alzheimer’s drug, Aduhelm (aducanumab) experienced brain swelling or bleeding.
However, most swelling was mild or moderate and occurred early in the treatment period, according to the Biogen-funded study published in JAMA Neurology.
Forty-one percent of patients in the combined 10 mg/kg Aduhelm group experienced amyloid-related imaging abnormalities (ARIA), and 35% experienced ARIA-edema. Twenty-six percent realized associated symptoms such as headache, confusion, dizziness, and nausea. ARIA-microhemorrhage occurred in 19%.
These abnormalities comprise a spectrum of imaging findings detected on brain magnetic resonance imaging and are associated with the use of monoclonal antibodies targeting amyloid-β (Aβ), including Aduhelm.
“Although ARIA can occur at any time, clinical suspicion for ARIA should be highest early in treatment, and routine surveillance MRIs should be supplemented with ad hoc MRIs in patients with new-onset symptoms potentially associated with ARIA,” the researchers wrote.
Biogen’s EMERGE and ENGAGE phase 3 trials included nearly 3,300 patients across 20 countries and constituted one of the largest ARIA data sets. The patients were enrolled August 2015 to July 2018, and the trials were terminated early in March 2019 based on a futility analysis, according to the JAMA Neurology article.
Aduhelm has been extremely controversial since its approval by the FDA in June. Following the lead of some commercial insurers, the U.S. Veterans Administration said this summer that it was declining coverage of Aduhelm on its National Formulary.
The VA’s decision is "due to the risk of significant adverse drug events and to the lack of evidence of a positive impact on cognition," a VA spokesperson told FormularyWatch®.
Some Blue Cross Blue Shield plans also said they won't cover Aduhelm, noting that Aduhelm is considered investigational due to insufficient evidence of clinical benefit and not applicable for consideration of medical necessity.
While VA’s PBM acknowledges the recent FDA decision on Aduhelm, “given the lack of evidence of a robust and meaningful clinical benefit and the known safety signal, we recommend against offering this agent to patients with Alzheimer’s dementia (mild or otherwise) or mild cognitive impairment,” the VA said in a notice.
The Biogen researchers noted that safety data collected while treating patients with aducanumab in real-world settings as well as clinical settings through the phase 3b EMBARK redosing trial and forthcoming FDA-mandated confirmatory clinical studies “will continue to inform best practices and characterization of ARIA in the clinic”.