The European Commission announced on Wednesday that it has officially approved a treatment designed to slow cognitive decline in certain patients with Alzheimer’s disease, following an endorsement from the European Medicines Agency (EMA). The authorization for this treatment, marketed under the name Leqembi, was granted on Tuesday and is based on the EMA’s scientific assessment, which determined that the benefits of the drug outweigh its risks, as emphasized in a statement by the Commission.
At the end of 2024, the European regulator recommended granting market approval for Leqembi (lecanemab) for “the treatment of mild cognitive impairment (memory and thinking disorders) or mild dementia due to Alzheimer’s disease (early-stage Alzheimer’s disease).” It is important to note that this approval applies only to patients who are at a lower risk of potential brain hemorrhage, specifically those with “one or no copies of the ApoE4 gene,” which is recognized as a significant risk factor for Alzheimer’s disease.
Leqembi, developed by the Japanese pharmaceutical company Eisai and the American manufacturer Biogen, received approval in January 2023 in the United States for patients who have not progressed to an advanced stage of the disease. It is also available in Japan and China. Despite decades of research, scientists have yet to achieve a true breakthrough in the battle against Alzheimer’s disease, which impacts tens of millions of individuals worldwide.
The European Commission’s approval marks a significant advancement in the treatment landscape for Alzheimer’s patients in the EU. Lecanemab is the first medication of its kind to be approved in the European Union, targeting the underlying disease processes rather than merely alleviating symptoms. Previously, Alzheimer’s therapies have only treated symptoms of the disease, not causative processes in the brain.
Experts have pointed out that only a very small portion of Alzheimer’s patients are eligible for this therapy. The drug is directed against amyloid deposits (a protein) in the brain and is intended to slow down the progression of the disease. The main measure of efficacy of lecanemab was the change in cognitive and functional symptoms after 18 months, which was measured using a dementia rating scale. Patients treated with lecanemab showed a slightly lower increase in the score after 18 months (1.22 compared to 1.75), indicating a slower cognitive decline, according to the EMA.
However, the therapy cannot cure the disease, and a drug to cure Alzheimer’s is still not in sight. If amyloid deposits have already caused irreversible damage to the brain, slowing their growth will not reverse damage. The treatment is only approved for individuals with mild cognitive impairment in the early stages of Alzheimer’s and is restricted to patients with a specific gene variant that will not cause side effects like swelling and bleeding in the brain.
Out of 1.2 million estimated Alzheimer’s sufferers in Germany, only a small proportion are eligible for the therapy, as reported by the German Centre for Neurodegenerative Diseases (DZNE). The Committee for Medicinal Products for Human Use (CHMP) had originally recommended against a marketing authorization for Leqembi in July 2024, but the EC’s recent decision marks a positive shift in the Alzheimer’s treatment landscape.
Christopher Viehbacher, President and Chief Executive Officer at Biogen, stated that the approval of lecanemab by the European Commission marks the thirteenth approval of this important medicine. He emphasized, “Lecanemab is the first treatment which showed that the reduction of the Aβ plaques in the brain is associated with the slowing of cognitive decline in patients at the early stage of the disease. This is a landmark advancement in a field where there has been no or little innovation in the past 20 years.”
Despite the promising results, the approval of lecanemab comes amid ongoing debates regarding its clinical significance. While both lecanemab and another drug, donanemab, have shown to slow cognitive decline by around 30%, the modest effects have sparked discussions about whether the benefits justify the high cost and potential side effects. Some clinicians argue that individuals may not notice a significant difference, while others believe that even a moderate slowdown delivers real benefits to patients and their families.
In the pivotal trial of lecanemab, 21.5% of participants developed brain swelling or bleeding, collectively known as amyloid-related imaging abnormalities (ARIA). This condition is usually asymptomatic, but about one-quarter of those affected experience confusion, headaches, or dizziness. Serious side effects, such as seizures and even death, have been reported, although they are rare. The risks associated with ARIA are thought to stem from antibodies binding to amyloid-β in blood vessels, leading to swelling due to neuroinflammatory reactions.
Researchers are exploring various methods to improve the safety and efficacy of amyloid-targeting therapies. For instance, a delivery approach known as a brain shuttle could enhance the concentration of drugs in the brain, allowing for lower doses and reduced side effects. Additionally, there is ongoing research into developing vaccines that could prompt the body to produce its own antibodies against amyloid-β, potentially offering a more straightforward and cost-effective treatment option.
As understanding of Alzheimer’s disease advances, there is a growing consensus that effective treatment may require targeting multiple aspects of the disease simultaneously. In addition to amyloid-β plaques, researchers are also focusing on tau tangles that accumulate inside neurons. Various potential anti-tau therapies are currently in early-stage trials, and combinations of these therapies with amyloid-targeting drugs are being tested in clinical trials.
Overall, the approval of Leqembi represents a significant step forward in Alzheimer’s treatment, but it also highlights the complexities and challenges that remain in addressing this devastating disease. With ongoing research and development, there is hope that more effective therapies will emerge, offering better outcomes for patients and their families.
