The first drug capable of slowing the rate of deterioration of Alzheimer’s patients has been discovered. The experimental drug, called lecanemab, is an antibody that targets the toxic clumps of amyloid protein associated with this mind-disturbing disease. While these results are cause for celebration, important questions remain about their safety and implementation.
Full results of the phase 3 trial of the drug lecanemab (the final phase of human testing) have been published in the New England Journal of Medicine. The trial showed that patients who received the drug had 27% slower disease progression after 18 months of treatment than those who received a placebo.
Are good news. For the first time we have a potential treatment that has a demonstrated effect on both the symptoms and the underlying pathology of Alzheimer’s disease. These results represent a breakthrough in the search for treatments for this devastating disease and are an important indication that the course of the disease can be altered.
But the results paint a mixed picture. On the one hand, it is the first drug that has been shown to have some effect in slowing down the progression of the disease. On the other hand, the apparent effects are slight and the risks are not negligible.
The overall trial involved about 1,800 people with early-stage Alzheimer’s. Participants were randomly assigned to receive intravenous lecanemab or placebo every two weeks. The study was “double-blind,” meaning that until the end of the trial neither the participants nor the investigators knew who was receiving the experimental drug and who was receiving the placebo.
Throughout the study, the participants’ disease progression was followed using the Clinical Dementia Rating Scale, which rates the patient based on their cognition and ability to live independently. The participants’ brains were also scanned for the two proteins commonly associated with Alzheimer’s disease: amyloid and tau.
Scores in both groups worsened over the 18 months of the study, but the rate of deterioration was slower in those who received lecanemab. Also, the magnitude of the slowdown, while statistically significant (not likely due to chance), was small: a reduction of 0.45 on an 18-point scale.
Some experts are concerned that this effect is not clinically significant. In a statement to the Science Media Centre, Rob Howard, professor of elderly psychiatry at UCL, said “none of the reported results, including the primary outcome, reached accepted levels of improvement to constitute a clinically significant treatment effect.” .
The success of lecanemab was also measured by the amount of amyloid and tau proteins in patients who received the experimental drug compared to those who received the placebo infusion. The results showed a reduction in these proteins in those who received lecanemab.
In fact, brain amyloid levels dropped below the threshold required for a positive diagnosis of Alzheimer’s. However, markers of brain cell death were not affected, indicating that amyloid in Alzheimer’s disease is just one mechanism in a complicated landscape of the disease.
Approximately one in four participants (26.6%) in the lecanemab group experienced brain swelling or bleeding in the brain (which can be minor or major). STAT, a medical news website, reported that a man died of a brain hemorrhage after receiving lecanemab, citing a possible interaction with his anticoagulant medication.
Shortly thereafter, the journal Science reported a second trial patient death, also after receiving treatment for a stroke. However, the drug’s developer, Eisa, told Science: “All available safety information indicates that lecanemab treatment is not associated with an increased risk of death overall or from any specific cause.”
However, given the potential for patients to take the drug for the rest of their lives, more research is needed on the safety and interactions with existing medications.
It is also important to find out how long the improvements in cognition last and whether the drug continues to slow the rate of decline or whether the results level off, or even decline.
It should be noted that only patients in whom a sufficient level of amyloid was detected in the brain or cerebrospinal fluid – requiring a PET brain scan or invasive lumbar puncture – were eligible to participate in this phase 3 trial. United Kingdom, Alzheimer’s is currently diagnosed through an interview with a doctor. Dr Susan Kohlhaas, the UK’s head of Alzheimer’s research, says the public health system is not ready for a new era of dementia treatment.
We estimate that unless there are drastic changes in the way specialized diagnostic tests for Alzheimer’s disease are accessed, only 2% of people eligible for drugs such as lecanemab will be able to access them.
Restructuring the dementia services of the UK health system to offer PET scans or lumbar punctures on a routine and timely basis would be a costly and lengthy process.
Based on the above results, Eisai applied to the US drug regulator (Food and Drug Administration) for expedited approval of his drug. A decision is expected on January 6, 2023. If the regulator grants rush approval, these latest results will likely support a full approval application.