A US Food and Drug Administration (FDA) expert panel has approved lecanemab, a new drug that delays cognitive decline caused by Alzheimer’s by 27%. The six experts who made up the panel decided to vote in favour, after a long session of debate, argument and data review.
The decision represents a tremendous boost to the final approval of this drug, which is the first in decades to show some, albeit modest, efficacy against the progression of a neurological disease that affects 50 million people worldwide.
The authority provisionally approved the use of this drug in January, as long as there is still no reliable data on its effectiveness. Today, the Advisory Committee on Drugs in the Nervous System, composed of six independent specialists, reviewed the results of the Clarity clinical study on the efficacy of lecanemab and unanimously decided that the results are compelling.
In the coming weeks, the FDA must decide whether to finally approve the drug, which would be indicated for people with early-stage Alzheimer’s. The agency basically follows the recommendations of the Advisory Board. The biggest uncertainty is whether the European Medicines Agency will also approve the drug, a decision expected in early 2024.
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Lecanemab, with the trade name Leqembi, is a monoclonal antibody. This molecule, injected intravenously, is said to target and help clear plaques of amyloid protein in the brain, which are a marker of disease. The Clarity study involved nearly 900 people between the ages of 50 and 90 with symptoms of early Alzheimer’s disease (cognitive and memory problems but no need for caregivers). Lecanemab showed that disease progression was 27% slower in treated patients. This percentage means that patients who took the drug progressed six months more slowly than those who did not take it during the 18-month clinical study.
The biggest success in decades
These are the best results for an Alzheimer’s drug in decades. However, the effect is so small that neither patients nor caregivers are likely to notice it.
The key is whether the effect of this antibody lasts beyond the 18 months that the trial lasted. If this were the case, the benefits of this new drug would be more noticeable and its use would increase.
Preparation in the Brain Bank of the CIEN Foundation in Madrid. CIEN FOUNDATION
Lecanemab is not without controversy due to its side effects such as cerebral hemorrhage and brain swelling. During clinical trials, three patients died with brain hemorrhages, possibly due to the drug and its interaction with anticoagulants.
In the clinical study, people who received the treatment experienced more side effects, including minor bleeding in the brain, although most of these were not serious. The incidence of major brain hemorrhage was greatly reduced in both the placebo and drug-taking patients, although it was six times higher in the lecanemab group; 0.6% vs. 0.1%. Side effects requiring discontinuation of treatment occurred in 7% of treated patients, compared to 3% in the placebo group.
The study showed that side effects are particularly common and severe in patients taking anticoagulants, drugs that are common in older people with heart problems. Lecanemab is also more dangerous for people with the E4 mutation in the APOE gene. It is precisely these people who would need the drug the most, since this mutation increases the risk of developing Alzheimer’s fivefold.
The committee today recommended genetic testing for patients before they take the drug to determine if they have the mutation. They have also recommended banning people from taking blood thinners or informing them of the risk they are running if they decide to take them.
shrink the brain
A few months ago, another study uncovered another surprising side effect. Lecanemab shrinks patients’ brains. The paper pointed out that it is not clear whether this effect can have an impact on patient health. In general, shrinkage of the brain is a clear indication of a disease of this organ. The Eisai company postulates that this decrease could be due to the disappearance of amyloid protein plaques, so it’s a sign of improvement.
In April, Eisai published a study that modeled the long-term effects of lecanemab. Their conclusions suggest the drug could delay the onset of more serious phases of the disease by almost three years.
Speaking before the committee meeting, Miguel Medina, associate scientific director of the Center for Network Biomedical Research on Neurodegenerative Diseases, said, “It would be a surprise if this drug didn’t get final approval in the United States and Europe.” clear results, even if they are modest,” he adds. The expert is aware that the launch of this new drug poses significant challenges. Lecabemab is given intravenously in hospitals and requires a scan, an amyloid protein test and two MRIs about every six months, Medina explains. “It can be difficult to implement this not only in large hospitals but also in medium-sized hospitals; and it will incur enormous costs,” he stresses.
“There is a solid clinical study with clear results, even if it is modest”
Miguel Medina, associate scientific director of the Networked Biomedical Research Center on Neurodegenerative Diseases
Another important question that still needs to be answered is how much the Leqembi will cost. Monoclonal antibodies are among the most expensive drugs in the world. Aducanumab — a lecanemab-like antibody being developed by Biogen for Alzheimer’s — cost $56,000 per patient.
Lecanemab is controversial, among other things because of the failure of its predecessor aducanumab. The Expert Group on the Nervous System did not recommend the drug’s approval, believing that its effectiveness had not been proven. Despite this, the FDA decided to approve it, leading to the resignations of several physicians who were on the expert panel. The drug was a failure.
But with lecanemab and other similar drugs, that could change the story. In May, pharmaceutical company Lilly announced that donanemab, another monoclonal antibody against the amyloid protein, slowed cognitive decline by 35%.
Since the German doctor Alois Alzheimer described the disease more than a century ago, no cure has been found and even the causes are unclear. The modest success of lecanemab and donanemab seems to indicate that the theory that the amyloid protein plays a leading role in the disease is correct, but probably not the only one responsible. Alzheimer’s poses a major challenge because development begins decades before the first symptoms appear. In addition to amyloid, there is another pathological protein associated with the disease: tau, and other studies suggest there may be other contributing factors, such as some infections.
David Pérez, head of neurology at the Hospital 12 de Octubre in Madrid, believes that the approval of the medicine should be accompanied by certain precautions, such as the creation of a register of patients receiving this medicine for special monitoring. “Given the uncertainties surrounding the safety and usefulness of this drug, approval in the context of specific indications and protocols and careful monitoring and prioritization of ideal candidates would make sense. “In an environment like Europe, with national health systems, it seems important to develop a strategy beforehand for their implementation and to prevent the collapse of neurological care services,” he emphasizes.
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