Tag: lecanemab

Categories : Neurodegenerative DiseasesTags :

Alzheimer’s Drug Lecanemab Well Tolerated in Real-world Use

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Side effects of lecanemab are manageable, study finds

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The Food and Drug Administration’s approval in 2023 of lecanemab – a novel Alzheimer’s therapy shown in clinical trials to modestly slow disease progression – was met with enthusiasm by many in the field as it represented the first medication of its kind able to influence the disease. But side effects of brain swelling and bleeding emerged during clinical trials that have left some patients and physicians hesitant about the treatment. [Especially considering its $26 500 per year cost – Ed.]

Medications can have somewhat different effects once they are released into the real world with broader demographics. Researchers at Washington University School of Medicine in St. Louis set out to study the adverse events associated with lecanemab treatment in their clinic patients and found that significant adverse events were rare and manageable.

Consistent with the results from carefully controlled clinical trials, researchers found that only 1% of patients experienced severe side effects that required hospitalisation. Patients in the earliest stage of Alzheimer’s with very mild symptoms experienced the lowest risk of complications, the researchers found, helping to inform patients and clinicians as they navigate discussions about the treatment’s risks.

The retrospective study, published in JAMA Neurology, focused on 234 patients with very mild or mild Alzheimer’s disease who received lecanemab infusions in the Memory Diagnostic Center at WashU Medicine, a clinic that specialises in treating patients with dementia.

“This new class of medications for early symptomatic Alzheimer’s is the only approved treatment that influences disease progression,” said Barbara Joy Snider, MD, PhD, a professor of neurology and co-senior author on the study. “But fear surrounding the drug’s potential side effects can lead to treatment delays. Our study shows that WashU Medicine’s outpatient clinic has the infrastructure and expertise to safely administer and care for patients on lecanemab, including the few who may experience severe side effects, leading the way for more clinics to safely administer the drug to patients.”

Lecanemab is an antibody therapy that clears amyloid plaque proteins, extending independent living by 10 months, according to a recent study led by WashU Medicine researchers. Because amyloid accumulation is the first step in the disease, doctors recommend the drug for people in the early stage of Alzheimer’s, with very mild or mild symptoms. The researchers found that only 1.8% of patients with very mild Alzheimer’s symptoms developed any adverse symptoms from treatment compared with 27% of patients with mild Alzheimer’s.

“Patients with the very mildest symptoms of Alzheimer’s will likely have the greatest benefit and the least risk of adverse events from treatment,” said Snider, who led clinical trials for lecanemab at WashU Medicine. “Hesitation and avoidance can lead patients to delay treatment, which in turn increase the risk of side effects. We hope the results help reframe the conversations between physicians and patients about the medication’s risks.”

Hesitation around lecanemab stems from a side effect known as amyloid-related imaging abnormalities, or ARIA. The abnormalities, which typically only affect a very small area of the brain, appear on brain scans and indicate swelling or bleeding. In clinical trials of lecanemab, 12.6% of participants experienced ARIA and most cases were asymptomatic and resolved without intervention. A small percentage (2.8%) experienced symptoms such as headaches, confusion, nausea and dizziness. Occasional deaths have been linked to lecanemab in an estimated 0.2% of patients treated.

The Memory Diagnostic Center began treating patients with lecanemab in 2023 after the drug received full FDA approval. Patients receive the medication via infusions every two weeks in infusion centers. As part of each patient’s care, WashU Medicine doctors regularly gather sophisticated imaging to monitor the brain, which can detect bleeding and swelling with great sensitivity. Lecanemab is discontinued in patients with symptoms from ARIA or significant ARIA without symptoms, and the rare patients with severe ARIA are treated with steroids in the hospital.

In looking back on their patients’ outcomes, the authors found the extent of side effects aligned with those of the trials – most of the clinic’s cases of ARIA were asymptomatic and only discovered on sensitive brain scans used to monitor brain changes. Of the 11 patients who experienced symptoms from ARIA, the effects largely resolved within a few months and no patients died.

“Most patients on lecanemab tolerate the drug well,” said Suzanne Schindler, MD, PhD, an associate professor of neurology and a co-senior author of the study. “This report may help patients and providers better understand the risks of treatment, which are lower in patients with very mild symptoms of Alzheimer’s.”

Source: WashU Medicine

Categories : Neurodegenerative DiseasesTags :

Shrinking Brain Volume may be Reflective of Alzheimer’s Treatment Efficacy

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Neurons in the brain of an Alzheimer’s patient, with plaques caused by tau proteins. Credit: NIH

Brain shrinkage observed in people receiving drugs for Alzheimer’s treatment actually reflects their efficacy, suggests to a new study from University College London. The researchers analysed data from a dozen different trials of amyloid-targeting immunotherapy – including lecanemab, recently approved in the UK for Alzheimer’s treatment but not yet used by the NHS.

While brain shrinkage is usually an undesirable outcome, the team found that the excess volume loss was consistent across studies and correlated with how effective the therapy was in removing amyloid and was not associated with harm.

As a result, the researchers believe that the removal of amyloid plaques, which are abundant in Alzheimer’s patients, could account for the observed brain volume changes. And, as such, the volume loss should not be a cause for concern.

To describe this phenomenon, the research team coined a new phrase: “amyloid-removal-related pseudo-atrophy” or ARPA. The team published their findings in published in Lancet Neurology.

Senior author and Director of the UCL Dementia Research Centre, Professor Nick Fox said: “Amyloid-targeting monoclonal antibodies represent a significant therapeutic breakthrough in the treatment of Alzheimer’s disease. These agents work by binding to and triggering the removal of amyloid plaques from the brain.

“One area of controversy has been the effect of these agents on brain volumes. Brain volume loss is a characteristic feature of Alzheimer’s disease, caused by progressive loss of neurons.

“Amyloid immunotherapy has consistently shown an increase in brain volume loss – leading to concerns in the media and medical literature that these drugs could be causing unrecognised toxicity to the brains of treated patients.

“However, based on the available data, we believe that this excess volume change is an anticipated consequence of the removal of pathologic amyloid plaques from the brain of patients with Alzheimer’s disease.”

In August, the Medicines and Healthcare Products Regulatory Agency (MHRA) licensed lecanemab, for use in the early stages of Alzheimer’s disease in the UK *.

The drug works by targeting beta amyloid – a protein that builds up in the brains of people with Alzheimer’s disease and is thought to be the triggering event leading to neuronal dysfunction and cell death.

The National Institute for Health and Care Excellence (NICE) that decide whether drugs should be made available on the NHS have published draft guidance advising that the benefits of lecanemab are too small to justify the cost to the NHS. However, the decision will be reviewed following a public consultation and a second independent committee meeting later this year.

Source: University College London

Categories : Neurodegenerative Diseases New Compounds and TreatmentsTags :

Third Alzheimer’s Drug is ‘Opening a Chapter in a New Era’

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With yet a third new Alzheimer’s drug, the monoclonal antibody donanemab, expected to be approved by the Food and Drug Administration (FDA), the field is beginning to show progress in the fight to slow the disease. But the drugs work best for those in the earliest stages of Alzheimer’s, and other therapies will be needed to help those with advanced disease, according to Gil Rabinovici, MD, director of the UCSF Alzheimer’s Disease Research Center.

This is likely “just the opening chapter in a new era of molecular therapies for Alzheimer’s disease and related neurodegenerative disorders,” Rabinovici wrote in an editorial that is being published along with the results of the latest drug, donanemab, in JAMA. Rabinovici was not involved in the trial.

Donanemab is a monoclonal antibody, like the two earlier Alzheimer’s drugs, aducanumab (Aduhelm) and lecanemab (Leqembi). These drugs attack plaques in the brain that are made of a protein called amyloid. They disrupt cell function and lead to the rapid spread of another protein called tau. Both amyloid and tau contribute to the development of Alzheimer’s disease.

The trial showed donanemab slowed cognitive decline by 35% compared with placebo in patients with low-to-intermediate levels of tau in the brain. These results are similar to those reported with Leqembi, which received FDA approval earlier this month. In the donanemab trial, patients also experienced a 40% lower risk of progressing from mild cognitive impairment to mild dementia, or from mild-to-moderate dementia.

Donanemab was better at removing amyloid plaques compared to Aduhelm and Leqembi. It reduced tau concentrations in the blood, but not in a key area of the brain.

While these results are encouraging, Rabinovici said an in-depth analysis still is needed to understand how these findings affect patient outcomes.

Limited benefit in advanced disease

Patients with more advanced disease showed little to no benefit compared to those who received the placebo. Together with the drug’s potentially serious side effects, this should push experts to “aim higher in developing more impactful and safer treatments,” wrote Rabinovici, who is affiliated with the UCSF Memory and Aging Center, departments of Neurology, Radiology and Biomedical Imaging, as well as the Weill Institute for Neurosciences.

Donanemab should be restricted to patients with low-to-intermediate levels of tau, which indicates mild disease. Other trials are evaluating how well monoclonal antibodies work in the earliest phase of the disease before symptoms appear.

Like the two other new Alzheimer’s drugs, donanemab was associated with ARIA, amyloid-related imaging abnormalities that may include brain swelling and microbleeds. Serious ARIA occurred in 3.7% of patients, including three deaths. Risks were higher among patients with the APOE4 gene, which is related to an increased risk for Alzheimer’s. For that reason, Rabinovici said, genetic testing should be recommended prior to monoclonal antibody treatment.

While ARIA has generally been managed safely in clinical trials, Rabinovici urged caution as these drugs enter into real-world practice. He suggested limiting access to patients with normal pre-treatment MRIs, repeating MRIs at regular intervals and stopping or suspending treatment when ARIA occurs.

Lack of racial and ethnic diversity was a major limitation of the trial. Just 8.6% of the 1,251 U. S. participants were non-white. Rabinovici said this raises ethical concerns about the “generalisability of results to populations at highest risk,” noting studies that have shown higher rates of dementia in Black and Latino populations.

Given the anticipated high cost of donanemab and high patient demand, Rabinovici said it might make sense to limit the treatment duration to the time needed to clear amyloid plaques from the brain, which is the approach pioneered in the trial. He said this could “greatly enhance the feasibility of treatment for patients, clinicians, insurers and health systems.”

Source: University of California – San Francisco

Note: this article previously used an incorrectly attributed image. This has since been taken down and replaced.

Categories : Neurodegenerative Diseases New Compounds and TreatmentsTags : 1 Comment

Alzheimer’s Drug Breakthrough Hailed as ‘Momentous’

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Photo by Matteo Vistocco on Unsplash

An 18-month randomised controlled trial of the new Alzheimer’s drug lecanemab has been hailed as “momentous” after encouraging Phase III trial results. The effects, while moderate, stand in contrast to virtually all other Alzheimer’s drug development efforts which have ended in failure.

According to the trial results published in the New England Journal of Medicine, lecanemab slows the rate of progression of Alzheimer’s by about 25%, though it is only really effective if the disease is caught early. Cognitive assessment scores as well as positron-emission tomography (PET) imaging of amyloid showed benefits.

This may be of great benefit to those who already know that they are already at risk of the disease, such as actor Chris Hemsworth who, at age 39, is taking a break from acting after he discovered that he has a high genetic risk of Alzheimer’s.

At present, the only FDA-approved drug to slow the progression of Alzheimer’s, Aduhelm, is of questionable benefit at best, is exorbitantly expensive and there has been an official probe into alleged irregularities in its approval process.

The 1975 trial participants were 50–90 years old with early Alzheimer’s disease (mild cognitive impairment or mild dementia due to Alzheimer’s disease) with evidence of amyloid on PET or by cerebrospinal fluid testing. Participants were randomised to receive intravenous lecanemab (10mg/kg of body weight every 2 weeks) or placebo.

The primary end point was the change from baseline at 18 months in the score on the Clinical Dementia Rating–Sum of Boxes (CDR-SB; range, 0 to 18, with higher scores indicating greater impairment). Key secondary end points included change in amyloid burden on PET, and on other cognitive impairment assessment scores.

 The mean CDR-SB score at baseline was approximately 3.2 in both groups. The adjusted least-squares mean change from baseline at 18 months was 1.21 with lecanemab and 1.66 with placebo. In a substudy involving 698 participants, there were greater reductions in brain amyloid burden with lecanemab than with placebo. Other cognitive assessments favoured lecanemab as well. Lecanemab resulted in infusion-related reactions in 26.4% of the participants and amyloid-related imaging abnormalities with oedema or effusions in 12.6%.