EXPLANATION | Could a new drug slow the progression of Alzheimer’s disease?

Story so far: In late November, news of a drug’s success in reducing cognitive decline in Alzheimer’s patients exploded on the horizon with all the promise of being a silver bullet. Co-developed by pharmaceutical companies Biogen and Eisai, lecanemab was tested in patients with early Alzheimer’s disease. The results of this study were presented at the Alzheimer’s Disease Clinical Trials Conference in San Francisco, USA. New England Journal of Medicine (NEJM) was moderately effective in arresting cognitive and functional decline in patients with early-stage disease. This brings hope to a world where an estimated 55 million people are living with Alzheimer’s disease.

What is lecanemab?

Lecanemab belongs to a class of drugs called monoclonal antibodies. These antibody-mediated drugs target beta-amyloid, the protein deposits found in Alzheimer’s patients, and disrupt cellular function.

Neuropsychiatrist Ennapadum. His S. Krishnamoorthy, founder of the Buddha Clinic in Chennai, said: This class of drugs does just that. ”

according to NEJM This paper is a multicenter, double-blind, phase 3 study conducted over 18 months in people aged 50 to 90 years with early Alzheimer’s disease (mild cognitive impairment or mild dementia due to Alzheimer’s disease). It is intended for Evidence of amyloid deposition. Participants were randomly assigned to intravenous lecanemab or placebo. It was observed that lecanemab “reliably cleared amyloid plaques.”

This was the primary endpoint of the study, demonstrating changes in scores recorded at baseline when the study began on the Clinical Dementia Rating-Box Sum (CDR-SB). Key secondary endpoints included changes in amyloid burden on PET (Positron Emission Topography). The researchers concluded that there was a change in both the lecanemab and placebo groups.

Could lecanemab be a silver bullet for the treatment of Alzheimer’s disease?

lancetIn an editorial, especially after such a long and fruitless wait for a successful treatment for Alzheimer’s disease, a phase 3 trial showing efficacy on clinical outcomes is welcome news.

However, according to indicators presented in previous studies, we point out that the observed differences in the CDR-SB scale may not be clinically meaningful. It was also cause for concern that one of the five patients developed an amyloid-associated imaging abnormality (ARIA).

lancet Given these concerns, the editorial concludes, “It remains to be seen whether lecanemab is the game-changer some have suggested.” , explains that they are evaluating whether lecanemab can prevent the development of dementia in patients with amyloid lesions but no clinical symptoms. There is none.”

Dr Krishnamoorthy said aducanumab, the first treatment for Alzheimer’s disease, has been approved in fast-track mode and has received much criticism. “Many experts were dissatisfied with the results of the trial that led to approval. Concerns were also expressed about

Lecanemab, on the other hand, appears to have had a modest effect on early dementia through both clinical improvement (CDR and ADAS-Cog rating scale scores) and reduction in amyloid plaques, he adds. “The same problems of swelling and bleeding in the brain may exist with this drug, and may apply to many antibody-mediated treatments,” he explains.

For practitioners like him, this is an opportunity to be “cautiously optimistic.” “This is definitely a step forward and offers hope, despite caveats such as eligibility criteria, intensity of treatment, need for imaging studies and high cost.” Only those in the course may benefit. It must be delivered via weekly IV injections and requires hospital visits and close monitoring. Also, to identify amyloid deposits, amyloid PET, which is not available in many developing countries, is required. As for the cost, lancet We speculate that it is likely prohibitive for low- and middle-income countries where most people with dementia live.

what is the future?

A first decision on approval of the drug by the FDA is expected by January 6, 2023, and by the European Medicines Agency later in 2023. lancetThe results of lecanemab “could well pave the way for the treatment needed for Alzheimer’s disease. But for now, presented at the 2020 Lancet Committee on Dementia Prevention, Intervention and Care, An important public health message about Alzheimer’s disease remains: maintaining brain health throughout life.”