First Alzheimer’s therapy recommended for approval in the EU

The European Medicines Agency (EMA) has given the EU the green light for the first time for an Alzheimer’s therapy that targets underlying disease processes. The agency recommended approval of the antibody lecanemab for the treatment of mild cognitive impairment (memory and thinking problems) or mild dementia in the early stages of Alzheimer’s disease.

Current Alzheimer’s therapies only treat symptoms of the disease, not causal processes in the brain. However, there is a limitation to the EMA recommendation: the drug should only be used for Alzheimer’s patients who have only one or no copy of ApoE4, a specific form of the gene for the protein apolipoprotein E. They are less likely to experience certain serious side effects – swelling and bleeding in the brain – than people with two copies of ApoE4.

The EU Commission responsible for approval usually follows the authority’s vote. The manufacturers of Lecanemab are the pharmaceutical companies Eisai (Japan) and Biogen (USA). In July, the EU Medicines Agency rejected approval: the risk of serious side effects from the antibody was said to be higher than the expected positive effect. The manufacturers had requested a second test.

The EMA’s Committee for Medicinal Products for Human Use (CHMP) has now concluded that in the limited population studied in the re-review, the benefits of lecanemab in slowing the progression of disease symptoms outweigh the risks. In the first review, no subgroup analyzes were taken into account, but all patients.

Of the patients treated with lecanemab with only one or no ApoE4 copy, edema occurred in 8.9 percent, with an average of 12.6 percent across all patients. Microbleeds occurred in 12.9 percent of patients with only one or no ApoE4 copy, compared to 16.9 percent of the broader population. In patients with only one or no copy of ApoE4 who were treated with placebo (a dummy treatment), the rates of swelling were 1.3 percent and bleeding was 6.8 percent, according to the EMA.

The main measure of effectiveness was change in cognitive and functional symptoms at 18 months, measured using a dementia rating scale (CDR-SB). The scale ranges from 0 to 18, with higher scores indicating greater impairment. Patients treated with lecanemab had a slightly smaller increase in the value after 18 months on average (1.22 versus 1.75). This indicates slower cognitive decline, said the EMA.

In its statement, the authority emphasizes that there must be measures to minimize risks. Before starting treatment and before the 5th, 7th and 14th lecanemab doses, patients must have MRI scans, and additional scans for warning signs such as headaches, visual disturbances and dizziness.

The antibody, which has been approved in the USA since the beginning of 2023 under the trade name Leqembi, is intended to remove the protein fragment beta-amyloid (Aß) from the brain. “Amyloid ß is probably at the beginning of a cascade of neuronal pathological changes in the brain,” said Jörg Schulz from the University Hospital of Aachen, spokesman for the “Dementia and Cognitive Disorders” commission of the German Society for Neurology (DGN).

In Germany, around a million people are affected by Alzheimer’s disease. The now recommended antibody Lecanemab does not improve the symptoms, but is only intended to slow down the progression of the disease. It is therefore only recommended for those affected in the early stages of the disease. The antibody is administered every two weeks through an intravenous infusion, which must be done under supervision.

Experts like Frank Jessen from the German Center for Neurodegenerative Diseases (DZNE) in Cologne assume that the drug will be available in Germany relatively quickly. However, it will probably be a while before there is a coordinated and responsible introduction of the therapy at the specialist centers. However, Jessen assumes that some doctors dispense the drug beforehand. “Because the pressure from patients is high. Many also say: I’ll pay for this out of my own pocket straight away.”