EU Recommends Approval of Leqembi for Early-Stage Alzheimer's
Key Insights
The European Medicines Agency (EMA) has recommended Leqembi for treating early-stage Alzheimer's, reversing its initial rejection due to brain swelling risks.
The recommendation is for patients without two copies of the Apoe4 (search) gene, who are less prone to ARIA side effects, requiring MRI monitoring during treatment.
Leqembi, already approved in the US and Japan, removes amyloid plaques (search) but has shown small cognitive benefits in trials, raising concerns about cost-effectiveness.
The European Union's drug regulator has shifted its stance and recommended Leqembi (lecanemab) for patients in the early stages of Alzheimer's disease (search). This decision, pending confirmation by the European Commission, marks a potential breakthrough as the EU's first treatment for Alzheimer's. The EMA's human medicines committee now supports the drug for a specific subset of patients, reflecting a more cautious approach than the original trial parameters.
Reversal of Initial Stance
Initially, the EMA rejected Leqembi due to concerns about the risk of amyloid-related imaging abnormalities (ARIA), including brain swelling and bleeding. The reversal followed a re-examination of trial data, specifically excluding data from patients with two copies of the Apoe4 (search) gene, which is associated with a higher risk of Alzheimer's and earlier onset. Patients with one or no copies of Apoe4 were found to be less likely to experience ARIA side effects.
The EMA now recommends Leqembi for this specific patient group, with mandatory MRI scans to monitor for ARIA before and during treatment. While no deaths from ARIA were reported during the 18-month clinical trial, some deaths have been reported in the US post-approval.
Clinical Perspectives and Concerns
Bart De Strooper, a neuroscientist at University College London, expressed relief that Europe is no longer in a "waiting room" regarding Alzheimer's treatment. Patient organizations like the Alzheimer's Association and Alzheimer Europe have also praised the decision.
However, experts hold differing views on Leqembi and similar anti-amyloid antibodies. Seb Walsh, a public health researcher at the University of Cambridge, noted, "The drugs are effective at removing amyloid from the brain, but the effects on people’s cognition and quality of life are small." He pointed out that trial participants were in the earliest stages of cognitive decline, where the disease progresses slowly. Walsh suggested that after 18 months, the difference between the average person on the drug and the average person on placebo would be difficult for a doctor to discern.
De Strooper acknowledges the limitations of the drug but emphasizes its potential for preventing further degeneration in the pre-clinical phase of Alzheimer's. This would require earlier diagnosis, screening, and stratified studies to identify patients who would benefit most.
Challenges and Future Directions
Walsh raised concerns about the small population likely to benefit from Leqembi, estimating that only about 8% of people with early Alzheimer's would have met the clinical trial eligibility criteria. He also highlighted concerns about long-term adverse effects and the significant resources needed for screening and treatment delivery.
In the UK, while Lecanemab was approved, the National Institute for Health and Care Excellence (NICE) concluded that its benefits were too small to justify the cost to the National Health Service (NHS), considering the need for frequent infusions and intensive monitoring.
Despite these challenges, other anti-amyloid antibodies are progressing. Eli Lilly has submitted donanemab for regulatory approval after positive phase 3 results. Roche is also developing trontinemab, an amyloid-clearing antibody with technology to cross the blood-brain barrier, showing promising interim results in early trials.
Walsh cautioned against overly optimistic headlines, emphasizing the need to temper expectations and avoid giving false hope to patients.