Details of the study

For the study, which has not yet been peer reviewed, Eli Lilly recruited 1,736 patients who were selected based on cognitive assessments and imaging to detect whether they had both amyloid and tau proteins.

Donanemab, similar to  Biogen's Aduhelm, targets and breaks up plaques of amyloid proteins associated with the progression of Alzheimer's disease.

Those in the study were stratified by their tau levels, and those whose tau levels and Alzheimer's symptoms were considered intermediate participated in the Phase 3 study, which totaled 1,182 people.

The patients were then given either donanemab or a placebo and were followed for 18 months. The researchers found that those who took the drug saw a 36% slowing of cognitive decline compared to the placebo group according to the Clinical Dementia Rating-Sum of Boxes. In addition, 47% of patients who took donanemab showed no decline at one year compared to 29% of those in the placebo group.

Donanemab did come with some side effects, including some incidents of amyloid-related imaging abnormalities (ARIA) — swelling and bleeding in the brain that is a known side effect of these types of drugs. The study saw brain swelling in 24% of patients and bleeding in 31.4%. According to Eli Lilly, the incidence of serious ARIA was 1.6% in the study, including two patients whose deaths were attributed to the complication and one patient who died "after an incident of serious ARIA."

Reaction

FDA recently rejected an application for donanemab because the agency wanted to see results from more people. According to Daniel Skovronsky, Eli Lilly's chief scientific and medical officer, the new study should satisfy those requirements.

"These are levels of efficacy that just haven't been seen before in Alzheimer's, setting a new benchmark for what's possible this disease," he said.

"We are encouraged by the potential clinical benefits that donanemab may provide, although like many effective treatments for debilitating and fatal diseases, there are associated risks that may be serious and life-threatening," said Mark Mintun, group VP of neuroscience research and development at Eli Lilly. "We note that these results suggest that people in the early pathological stage of disease could be the most responsive to therapeutics targeting amyloid."

Anne White, EVP of Eli Lilly and president of  Lilly Neuroscience, said she believes the data "meets the 'high level of evidence' [CMS] has described as the trigger for reconsideration of its National Coverage Determination. People with early Alzheimer's disease need and deserve full coverage and access for approved therapies."

"The progress we've seen in this class of treatments, as well as the diversification of potential new therapies over the past few years, provides hope to those impacted by this devastating disease," said Maria Carrillo, chief science officer for the  Alzheimer's Association.

However, Lon Schneider, a professor of psychiatry at the  University of Southern California's Keck School of Medicine, noted that the findings in the study suggest the benefits of donanemab are modest and may be outweighed by safety risks for some patients. (Vinluan, MedCity News, 5/3; Loftus, Wall Street Journal, 5/3; Twenter, Becker's Hospital Review, 5/3; Weixel, The Hill, 5/3)

There have been a lot of news stories about pharmaceutical treatments for memory care disorders. Healthcare leaders and patients are hoping for an effective treatment for Alzheimer's and other dementias. To understand how likely this is, we examine the state of the memory care drug pipeline, and explore the effects of the pipeline analysis in this blog.