At first there is just a certain agitation. Again and again the right word is missing, more and more often something is forgotten. Then the language problems increase. A lack of orientation becomes a problem, everyday life becomes a burden. At some point, the present and the past become blurred. The world becomes a maze, physical deterioration increases. People from the past are disappearing - it's a farewell in installments.
Alzheimer's is the most common form of dementia. According to the German Alzheimer Society, around 440,000 people over the age of 65 were newly diagnosed with dementia in 2021 alone. Alzheimer's cannot be cured. A manufacturer now claims to have found a way to at least slow down the progression of the disease. Is this the expected game changer?
According to the study by the manufacturer Eli Lilly, the new Alzheimer's drug donanemab manages to slow down the progression of the disease in the early stages. The US pharmaceutical company Eli Lilly announced that an application for approval from the US Food and Drug Administration (FDA) will be made before the end of this quarter. Experts speak of "real progress", but also warn of side effects.
The antibody donanemab recognizes in the brains of patients a form of the peptide amyloid-β, which accumulates in amyloid plaques in the brains of people with Alzheimer's disease. Such deposits of proteins in the brain appear years before the first symptoms and are characteristic of Alzheimer's. The new drug aims to remove these deposited plaques, rather than just preventing new plaques from being deposited or existing plaques from growing.
In an 18-month so-called phase III study with more than 1700 participants, the people who had received donanemab showed around 35 percent less cognitive impairment than those who had received a dummy drug, according to the company. There were also improvements in everyday use. According to this, after 18 months of treatment, the patients were 40 percent less impaired in activities of daily living than the placebo group.
How these results are to be assessed is still under discussion. "In my opinion, this is the first outstanding treatment success for Alzheimer's disease with an antibody," says Hans-Ulrich Demuth, Professor at the Fraunhofer Institute for Cell Therapy and Immunology. He refers to the significant reduction in plaque levels in a third of the patients after six months, after one and a half years of treatment more than 70 percent of the participants would have ended the study with the "result of complete plaque clearance".
Christian Haass, who heads the department for neurodegenerative diseases at the Ludwig-Maximilians-University in Munich, also assesses the development positively and is cautiously optimistic. With a view to the side effects and a better effectiveness of the therapy, there is certainly still a lot to be improved, according to Haass. However, reducing amyloid is "certainly the right approach to at least slow down the disease". And: "One thing should now finally be clear, the amyloid hypothesis is no longer a hypothesis, but a fact!"
Stefan Teipel also rates the data as encouraging. The euphoria of the head of the research group Clinical Dementia Research at the German Center for Neurodegenerative Diseases is still limited. In summary, all previous results speak for a detectable but small effect of amyloid antibodies on cognitive performance over 18 months. "For the individual patient, the positive effect will hardly be noticeable after 18 months. The hope is that the effects will last over a longer period of time, but this has not yet been shown," says Teipel.
The drug Leqembi, which follows a similar approach, was approved in the USA in January (more about Legembi here). It was developed by the US company Biogen together with the Japanese pharmaceutical company Eisai and contains the antibody lecanemab. The antibody binds the soluble amyloid-β molecules and thus prevents plaque formation.
The study results on donanemab are "real progress for the patients," said Frank Jessen, director of the Department of Psychiatry and Psychotherapy at the University Hospital in Cologne, the German Press Agency. In principle, the effect of donanemab and lecanemab is comparable. "For a precise comparison, you have to see the study data and hopefully also gain comparative experience with these substances in the future in Germany."
"Unfortunately, donanemab is not a game changer either," said Linda Thienpont, Head of Science at the Alzheimer's Research Initiative, but the drug could be a next step in the right direction. "It can neither cure nor stop Alzheimer's disease, but also, like lecanemab, at least slow down cognitive decline." However, Thienpont once again underlined the sometimes severe side effects such as brain swelling and cerebral hemorrhage, the effect was "bought dearly".
Source: PM manufacturer Eli Lilly, German Alzheimer Society, with material from dpa and the Science Media Center