Lilly Alzheimer’s drug slowed disease by roughly half a year, new results show

17 Jul 2023
www.biopharmadive.com
Clinical ResultDrug ApprovalClinical Study
A closely watched experimental drug for Alzheimer’s disease slowed the decline patients typically experience by about half a year in a key clinical trial, according to new results released Monday.
The drug, called donanemab, is being developed by Eli Lilly and works in a similar way as two other medicines recently approved in the U.S. to treat Alzheimer’s. These therapies are designed to break up clusters of “amyloid beta,” a mutated protein that forms toxic brain plaques and has long been viewed as a root cause of the disease.
In May, Lilly announced donanemab succeeded in a large, late-stage study that enrolled more than 1,700 people with early forms of Alzheimer’s. The drug effectively cleared amyloid from the brain, and patients treated with it declined around 35% slower on a disease rating scale than those given a placebo. Encouraged by the results, Lilly said it would submit an approval application to the Food and Drug Administration before the end of June.
On Monday, the company provided a more detailed look at the trial data during a presentation at the Alzheimer's Association International Conference, an annual research meeting. After a year and a half of treatment, donanemab delayed disease progression by roughly five to seven months in certain patients.
“We agree this is a starting point, but wow, what a starting point,” Mark Mintun, Lilly’s head of neuroscience research and development, said during a press conference Monday.
John Sims, another Lilly neuroscience executive, compared these initial amyloid-targeting therapies to drugs for diabetes. “Diabetes doesn’t have a cure, either, but it doesn’t mean you can’t have meaningful treatments,” he said at the press conference.
Along with its presentation, Lilly disclosed it had completed its approval application to the FDA and expects a verdict by the end of the year. The results were also published in the medical journal JAMA.
Until recently, there were no medicines approved in the U.S. to treat the underlying cause of Alzheimer’s. That changed in mid-2021 with the conditional clearance of Biogen and Eisai’s Aduhelm, though use of the drug has been extremely limited due to conflicting data and controversy surrounding its high price.
Biogen and Eisai have since secured full approval of another amyloid-targeting therapy, Leqembi, which is backed by more consistent clinical trial results and is expected to have much broader use.
Donanemab, should it gain approval, would help affirm the prominent theory that mutated amyloid is a main driver of Alzheimer’s. This so-called amyloid hypothesis has faced increased scrutiny in recent years, due to the many failures of other experimental therapies.
Lilly also examined the role played by “tau,” another protein tied to Alzheimer’s. Tangles of this protein usually grow in the brain as the disease advances, and Lilly focused its study analysis on people with low or intermediate levels.
“It was just a short year ago we were still arguing about how removing amyloid and tau might not have any benefit,” Maria Carrillo, the Alzheimer’s Association’s chief science officer, said during Monday’s press conference. “Now there’s evidence that really will propel the entire field into looking into these other markers [of disease]. It’s important to double down and not slow down.”
Though donanemab could become a valuable new option for some of the estimated 6 million Alzheimer’s patients in the U.S., it doesn’t work for everyone. Participants who entered Lilly’s study with high amounts of tau, for example, didn’t benefit from the drug, the fuller data showed.
In the JAMA paper, the study’s authors wrote that this outcome “supports the hypothesis that a greater benefit from amyloid-lowering therapies may occur when initiated at an earlier disease stage.”
The degree of benefit offered by donanemab is also a matter of debate, particularly as Lilly’s drug, like Aduhelm and Leqembi, comes with the risk of brain swelling and bleeding. Three participants in Lilly’s trial with serious signs of these so-called ARIA side effects later died.
“Slowing progression by a quarter to a half a year as seen with donanemab allows for someone to remain in [mild cognitive impairment] or mild-stage dementia for just that much longer,” wrote three physicians in an editorial published alongside the data.
“The modest benefits would likely not be questioned by patients, clinicians, or payers if amyloid antibodies are low risk, inexpensive, and simple to administer,” they added. “However, they are none of these.”
Alzheimer’s experts have argued that testing for amyloid and, in the case of donanemab, tau will add further costs to treatment and may stretch the resources of smaller treatment centers.
Additionally, Lilly’s results are hindered by how few people of color were enrolled in its trial, and the cap on participants’ age of 85 years, limiting the data available for groups heavily impacted by the disease.
“Similar to previous trials of [Leqembi] and [Aduhelm], this donanemab trial does not provide sufficient evidence of safety or efficacy among people racialized as American Indian or Alaska Native, Asian, Black, or Hispanic,” wrote Jennifer Manly, of Columbia University, and Kacie Deters, of the University of California, Los Angeles, in another JAMA editorial.
Jonathan Gardner contributed reporting
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