Drugs hailed as game-changers in the treatment of Alzheimer’s disease, a type of dementia, carry risks that may outweigh any benefit, scientists warned UK media on Sunday.
UK regulators are expected to decide next week on whether or not to approve the drug lecanemab, which was greenlit by US regulators last year, and donanemab, which is currently awaiting approval.
However, the drugs, which manufacturers say slow cognitive decline by clearing out amyloid protein in patients’ gray matter, are also known to shrink patients’ brains, and as many as a third of those who receive them also experience side effects classified as “amyloid-related imaging abnormalities” (ARIA) - a catch-all term that includes the swelling and bleeding of the brain.
About 1% of patients have side effects so severe they are fatal or require hospitalization, and the US Food and Drug Administration has required lecanemab’s manufacturer Esai to include a “black-box warning” on its label signaling the possibility of serious adverse events.
“When I look at an MRI scan that shows ARIA, it reminds me of looking at MRI scans of patients who’ve had strokes or some sort of traumatic brain injury,” University College of London Institute of Mental Health Professor Rob Howard told reporters, adding that imaging data shows patients receiving the drugs “are actually losing probably slightly more than a teaspoon full of brain.” According to Dr. Madhav Thambisetty, a senior clinical investigator at the US National Institute on Aging, patients receiving the largest dose have lost up to three teaspoons of brain volume.
While the drugs’ manufacturers hail their supposed potential to slow cognitive decline in Alzheimer’s patients by 27% (lecanemab) and 35% (donanemab) compared to a placebo, this translated to just a 0.45 point improvement on the 18-point Alzheimer’s symptom assessment scale - where improvements under one point are unlikely to be felt by either doctor or patient, according to Thambisetty. Even the drugs’ own publicity materials acknowledge they cannot restore memory or cognitive function that has been lost already.
Meanwhile, brain shrinkage is considered an indicator of Alzheimer’s itself, raising questions about the utility of a “treatment” that may worsen the underlying pathology. Some patients with ARIA have experienced deteriorations in cognitive ability five times that of an unmedicated Alzheimer’s patient, according to clinical trial data, and one woman in the Lecanemab trial died in hospital with a 7cm brain hemorrhage.
A similar drug also hailed as a miracle treatment for Alzheimer’s when it was approved in 2021, aducanumab, is set to be discontinued by its manufacturer this year. A review of the clinical data showed patients receiving the drug in high doses were more than 15 times as likely as those receiving a placebo to experience brain swelling and almost three times as likely to experience brain bleeding.