Alzheimer’s disease is a progressive, irreversible, neurodegenerative disease most common among people over the age of 65. It causes cognitive decline and in its late stages also loss of motor function and leads to a premature death. Currently there are four therapeutic options in EU that only address the symptoms of the disease and slow cognitive decline only for a short period of time. But in June 2021 there was new hope in this field in the form of the first biological drug approved by the FDA. Aducanumab (brand name Aduhelm) is a human monoclonal antibody that targets aggregated forms of amyloid beta (Aß) in the brain. Its mechanism of action is based on the so-called amyloid hypothesis that proposes the development of Alzheimer’s disease due to deposits of Aß and tau protein in the brain. This news was indeed welcomed by the patients and their families but was met with criticism in the scientific community. Aducanumab received its approval due to its proven effect on surrogate markers but there’s still doubt whether Aß can be recognized as a surrogate marker or, on the other hand, Aβ plaque deposits are simply a result of the disease. There have been multiple studies designed to test the amyloid hypothesis in the last 30 years, but no monoclonal antibody had a significant effect on slowing cognitive decline, even though many proved to be effective at removing Aß deposits. And even EMERGE, the Study that made the approval of aducanumab possible, was viewed as controversial since ENGAGE, a Study with an identical design did not prove effective at slowing cognitive decline despite its effect on Aß deposits. Therefore, our focus was on analyzing studies of aducanumab and other amyloid beta-targeting antibodies to assess their clinical efficacy and safety. We analyzed the primary and secondary goals of studies and concluded that aducanumab did not show a clinically important difference compared to placebo, since it did not reach at least 1-2 points of a difference on the clinical assessment of dementia progression scale CDR-SB. We also found that there were no major safety concerns and therapies were well tolerated among patients despite a high incidence of cerebral edema. There are new emerging studies in this field, with lecanemab (another anti-Aβ monoclonal antibody) showing similar results as aducanumab in EMERGE, which could lead to the approval of lecanemab in the EU. However, questions about the clinical significance of the effects of these drugs, validity of the amyloid hypothesis, treatment costs, and safety in a non-clinical environment remain.
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