Shares in Eli Lilly, a pharmaceutical company, have surged after its experimental drug, donanemab, showed promising results in the final-stage trial for Alzheimer’s disease. The drug was able to slow the progression of the disease by 35% over 18 months in a trial of 1,182 patients with early-stage Alzheimer’s. Despite the positive results, 24% of subjects on the drug experienced brain swelling and 31% had bleeding in the brain, side effects that have been seen with similar drugs.
Eli Lilly plans to apply for US approval for donanemab this quarter, following the successful trial. 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. This bolsters 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’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.
Mark Mintun, Lilly group vice president for neuroscience R&D, stated that “We think this is actually a level of efficacy not seen in previous trials.” However, 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 hospitalisation or even death. In Lilly’s final-stage trial, three patients who had received donanemab died after experiencing such side effects. The company did not release details as to whether these patients had brain swelling, brain bleeding, or both.
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%. However, in January, the US Food and Drug Administration said it would not 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, despite 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.
The positive results from the donanemab trial provide hope for those living with Alzheimer’s disease and their caregivers. However, the potential side effects of the drug cannot be ignored, and further research is needed to determine its long-term effectiveness and safety.