Promising Alzheimer’s drugs were doused in cold water, experts say

More than a year after Aducanumab was approved by the FDA (American drug regulatory agency in the United States), there is still little evidence that anti-amyloid drugs cause significant improvements in the memory and mental capacity of Alzheimer’s patients.

Experts heard by Sheet were unanimous in considering the new treatment as a cold water bath.

Aducanumab, from Biogen, and other similar drugs, such as Lecanemab or Gantenerumab, have shown great promise for the treatment of the disease in recent years. These drugs are monoclonal antibodies that innovate by combating beta-amyloid molecules, which, together with tau proteins, accumulate in the brain of patients and are known as the main biological hallmarks of the disease.

Paulo Caramelli, doctor in neurology and professor at UFMG (Federal University of Minas Gerais), says that anti-amyloid drugs manage to remove these proteins from the brain of patients, but this effect does not translate into clinical improvements, such as gains in cognition and alterations in memory, agitation or insomnia.

The controversies began during the approval of Aducanumab. Significant improvement in patient health was only observed in one of the two phase 3 clinical studies submitted to the FDA. In the expert committee set up by the regulatory agency to assess the case, ten of the eleven members recommended the need for new tests before launching the product on the market.

Even so, the cabinet decided to approve it, subject to the presentation of new studies within two years.

Lecanemab, also from Biogen, was able to improve the clinical conditions of participants in a phase 3 study by 27%, according to results released at the international conference Clinical Trials on Alzheimer’s Disease. According to Professor Caramelli, the earnings are below what doctors would like to offer patients and their families.

Furthermore, it is possible that the results are significant when the drug is used in patients in earlier stages of neurodegeneration. These data should be raised in studies conducted in the coming years.

Scholars from different research centers in France combined in a meta-analysis the clinical efficacy and safety data published in the phase 3 studies of Aducanumab and the phase 2 studies of Lecanemab and Donanemab (another anti-amyloid).

In this research, experts conclude that immunotherapies produce positive clinical effects on patients’ cognitive decline after 18 months of use, but consider the results below the minimum acceptable values ​​and, therefore, concluded that the risk-benefit ratio of these drugs is questionable.

For the UFMG specialist, the data obtained in the researches reduce the prospects of treating Alzheimer’s by removing beta-amyloids, as there is a lack of robust evidence on their role in the symptoms of the disease. The new drugs are capable of slowing down the progression of the disease, but they do not have the effect of reversing the symptoms.

Despite this, the Lecanemab results could put these drugs back at the center of the debate, as the relative stability of the disease’s progress is seen as a great gain.

Another area that has advanced in recent years has been the diagnosis of Alzheimer’s with the popularization of tools that allow the physiological assessment of the patient. In 2022, the first positron emission tomography devices capable of estimating the density of beta-amyloid proteins in the brain began to operate commercially in Brazil. Until then, they were only available to researchers.

Despite the innovations, Ivan Okamoto, a doctor in neurology and physician at Albert Einstein Hospital, says that clinical exams should continue to be the fundamental basis of diagnoses, since the alternatives are expensive and are only available in the private health system for a few patients. In addition, tests such as CSF are very invasive.

According to the expert, it is possible to present a diagnosis for 85% of Alzheimer’s cases with assessments made in the office itself. The doctor should trace the patient’s history, perform strength and cognition tests and, in some cases, simple CT scans or MRI.

“The new exams come for atypical, more difficult cases, to increase the accuracy to 95%. These are situations of early disease in younger people, or with unusual initial symptoms, such as changes in language”, he says.