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Eli Lilly & Co.’s shares climbed in premarket trading after its experimental drug for Alzheimer’s slowed the progress of the disease in a final-stage trial, paving the way for the company to apply for US approval.
The drug, donanemab, slowed the disease by 35% over a year and a half in a trial of 1,182 patients with early-stage Alzheimer’s, Lilly said Wednesday in a statement.
About 24% of subjects on the drug experienced brain swelling and an overlapping 31.4% had bleeding in the brain, side effects that have been seen with similar drugs. The company said it plans to apply for US approval this quarter, and the shares rose 5.2% in trading before US markets opened.
The results represent the second time Alzheimer’s was slowed in a final-stage trial by a drug that clears a brain protein called amyloid. They bolster the controversial theory that the abnormal protein plays a key role in the disease.
The success means patients and their caregivers could soon have another therapy shown to slow the disease alongside Eisai Co.’s Leqembi, which was approved in January.
The study is also a vindication for Lilly, which has spent billions of dollars and decades of research time on Alzheimer’s drug development.
"We think this is actually a level of efficacy not seen in previous trials,” said Mark Mintun, Lilly group vice president for neuroscience R&D, in an interview.
The price of the new drug will be in the range of similar therapies, Chief Executive Officer Dave Ricks told CNBC. Leqembi, the product from Eisai and partner Biogen Inc. that was the first to slow Alzheimer’s in a final-stage trial, received expedited US approval in January and has a list price of $26,500 a year.
The partners have applied for full approval based on a final-stage trial that showed it slowed cognitive and functional decline by 27% on a slightly different scale.
Full approval is important for Alzheimer’s drugs, because the US Medicare program has indicated it won’t broadly cover amyloid-lowering drugs without it.
The Medicare program that covers US older and disabled people has said it will only cover the new dementia drugs in tightly limited clinical trials until more evidence that they work is available.
Most analysts praised the results. Citigroup’s Andrew Baum called it the "new gold standard” in Alzheimer’s drugs, while Paresh Malhotra, professor of clinical neurology at Imperial College London said "we are now entering the treatment era of Alzheimer’s disease.”
Side Effects
One significant drawback of amyloid-lowering antibodies such as donanemab is that they can cause brain swelling and bleeding. While most of these cases do not cause symptoms, they can lead to hospitalization-or worse.
In Lilly’s final-stage trial, three patients who had received donanemab died after experiencing such side effects. The company didn’t release details as to whether these patients had brain swelling, brain bleeding or both.
Bloomberg Intelligence analysts John Murphy and Sam Fazeli said the trial suggests Lilly’s drug doesn’t have a strong competitive edge versus rival Leqembi.
"While reduction in the pace of disease progression with Lilly’s donanemab was similar to Leqembi over 18 months, the rates of serious complications were worse,” they wrote in a note. They also pointed to a higher rate of brain bleeding in the Lilly trial.
The trial also looked at a population of 552 patients who were deemed to be at a greater level of disease severity based on brain scans. When that group was combined with the larger, less acute population, the drug showed less impressive results, slowing the progress of the disease by 22% over 18 months.
Lilly had tried to get accelerated approval for donanemab based on its ability to lower amyloid in the brains of patients.
A mid-stage trial published in 2021 showed that donanemab slowed decline from Alzheimer’s disease by 32%. But in January, the Food and Drug Administration said it wouldn’t clear the drug because not enough of the subjects had received the drug for a full 12 months.
That setback put the focus on Lilly’s larger, final-stage trial.
Over the years, most human studies of amyloid-lowering drugs have fallen short or produced mixed results in Alzheimer’s patients, in spite of research linking the abnormal protein to the disease.
Companies have begun testing drugs at earlier stages of Alzheimer’s, hoping to show greater impact on cognitive decline, and have developed more-potent amyloid removers such as donanemab.
Lilly will present the results of the trial at an Alzheimer’s conference in July.
