New data question short-term efficacy of anti-amyloid drug
New research is raising questions pertaining to the effectiveness of a newer Alzheimer’s treatment that has been proven to reduce cognitive symptoms related to the disease.
Lecanemab, sold under the brand name Leqembi, was approved by the U.S. Food and Drug Administration in January 2023. The monoclonal antibody treatment treats early Alzheimer’s disease (AD) by essentially scrubbing the brain of amyloid-β (Aβ) plaques.
The drug’s approval was roundly celebrated at the time, as clinical trials suggested it could reduce Alzheimer’s-related cognitive decline by up to 27%. Post-approval data has been positive as well, but new research out of Osaka Metropolitan University in Japan is prompting new questions on the mechanisms that underlie the drug’s therapeutic effects.
Published in the Journal of Magnetic Resonance Imaging, the findings suggest lecanemab does not change the waste clearance function in the brains of AD patients in the short term. This could indicate that the medication does little to treat the nerve damage AD has inflicted on the glymphatic system, which clears waste from the brain, prior to starting the treatment.
Researchers used diffusion tensor imaging to analyze the brains of patients who had been diagnosed with AD and opted for treatment via lecanemab infusions. Scans were conducted three months prior to and after initiating treatment. The team focused on identifying changes in participants’ glymphatic function after starting treatment.
“Diffusion tensor imaging along the perivascular space (DTIALPS) index has emerged as a noninvasive surrogate marker suggested to be associated with glymphatic activity,” Tatsushi Oura, with the department of diagnostic and interventional radiology at the university, and colleagues explained. “This index declines with normal aging and is significantly lower in patients with AD than in cognitively normal individuals. Although disease-modifying therapy (DMT) may affect the DTI-ALPS index, no studies have examined longitudinal changes in the DTI-ALPS index following DMT initiation.”
The findings caught the team by surprise. When comparing pre- to post-treatment imaging, they did not observe significant differences in the DTI-ALPS index. This suggests that, although lecanemab may be able to slow the progression of cognitive decline, it does little to reverse damage done by AD prior to treatment.
"The absence of early DTI-ALPS index improvement suggests that even though DMT reduces plaque burden, the diffusion properties of perivascular spaces measured by DTI-ALPS do not change in the short term,” the authors wrote. “DMT can reduce plaque burden and slow further cognitive worsening but does not restore lost function, likely reflecting the fact that neuronal damage and clearance system deficits have already been well established.”
Read more about the team’s findings here.
In addition to her background in journalism, Hannah also has patient-facing experience in clinical settings, having spent more than 12 years working as a registered rad tech. She began covering the medical imaging industry for Innovate Healthcare in 2021.