2023-07-17 18:16:58
The scientific magazine ‘JAMA’ has published on Monday the results of a phase 3 trial with the drug donanemab, from the pharmaceutical company Lilly, which show it slows cognitive decline by 35 percent, compared to placebo in patients with low to intermediate levels of tau in the brain.
Donanemab is a monoclonal antibody, like the other two new Alzheimer’s drugs, aducanumab (‘Aduhelm’) and lecanemab (‘Leqembi’). These drugs attack brain plaques made of a protein called amyloid. They disrupt cell function and cause the rapid spread of another protein called tau. Both amyloid and tau contribute to the development of Alzheimer disease.
Approval in the United States this month
In the study, donanemab cleared amyloid plaques better than Aduhelm and Leqembi, and reduced tau levels in the blood, but not in a key area of the brain. These results are similar to those obtained with ‘This team’, which received US approval earlier this month.
In the donanemab trial, patients also experienced a 40 percent lower risk of transitioning from mild cognitive impairment to mild dementia, or mild to moderate dementia. On average, disease progression slowed between 4.4 and 7.5 months over 18 months.
In May, Lilly announced that it would work with the United States and other countries globally to “get the drug approved in the shortest amount of time possible.” The US already rejected accelerated approval of donanemab in January due to the limited number of patients who had been exposed to the drug for at least 12 months in a clinical study.
New era
In an editorial accompanying the study in the journal ‘JAMA,’ the director of the Alzheimer’s Disease Research Center at University of California at San Francisco (United States), Gil Rabinovici, has highlighted that the arrival of this new drug against Alzheimer’s shows that progress is being made in the fight to stop the disease.
However, he points out that these drugs work best in the early stages of the disease and other therapies will be needed to help people with advanced disease.
In any case, consider that it is “just the opening chapter of a new era of molecular therapies for Alzheimer’s disease and other related neurodegenerative disorders.
Although these results are encouraging, Rabinovici notes that further analysis is still needed to understand how these findings affect patient outcomes. For example, he details that patients with more advanced disease showed little benefit compared to those who received placebo.
Like the other two new Alzheimer’s drugs, donanemab was associated with ARIA, amyloid-related imaging abnormalities that can include brain swelling and microbleeds. Severe ARIAs occurred in 3.7 percent from the patientsincluding three deaths.
The risks were higher among patients with the APOE4 gene, which is linked to an increased risk of Alzheimer’s. Therefore, according to Rabinovici, genetic testing should be recommended before treatment with monoclonal antibodies.
Although ARIA has generally been treated safely in clinical trials, Rabinovici has urged caution when these drugs are introduced into real-world practice. For example, he has suggested limiting access to patients with magnetic resonance imaging (MRI) normal prior to treatment, repeat MRIs at regular intervals, and interrupt or discontinue treatment when ARIA occurs.
Given the expected high cost of donanemab and high patient demand, Rabinovici has stressed that it might make sense to limit the duration of treatment to the time needed to clear amyloid plaques from the brain. “This could greatly improve the feasibility of treatment for patients, clinicians, insurers and healthcare systems,” he said.
Available in one or two years
On the other hand, Liz Coulthard, associate professor of Dementia Neurology at the University of Bristol (United Kingdom), has defended in statements to SMC that the results of the study “are encouraging and mean that in one or two years it will be possible to offer patients a series of treatments that slow the progression of Alzheimer’s disease.
According to the expert, the drug appears to have “significant benefit, at least for some patients.” However, she points out that “it is not yet known if this benefit would continue after 18 months.”
In the same line, Ivan Koychev, principal clinical investigator and neuropsychiatrist for the Dementia Platform UK and the University of Oxford (United Kingdom), has ensured that the results published this Monday “add new evidence that immunological therapies that successfully eliminate amyloid plaques are associated with a modest slowdown in the progression of Alzheimer’s disease “.
In the future, the expert considers that the next stage consists of “finding out what the long-term results of those who have followed the therapy are: we still do not know when patients would stop treatment in the real world,” he stressed in statements to SMC.
#Advance #Alzheimers #drug #slows #cognitive #decline