Lilly provides update on A4 study of solanezumab for preclinical Alzheimer's disease.

The treatment did not clear plaque or halt accumulation of amyloid in participants treated with the drug in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's disease (A4) Study.

"Results of the A4 Study clearly showed that the primary and secondary endpoints were not met. Therefore, the A4 Study concludes our clinical development of solanezumab and indicates that targeting soluble amyloid beta through this mechanism is not effective in this population," said John Sims, head of medical, global brand development – solanezumab, for Eli Lilly and Company. "While this study was negative, the unique data generated have increased our understanding of preclinical Alzheimer's disease and will advance the next generation of AD prevention studies. Raw data and analyses will be made widely available to researchers through the public-private partnership with the NIH-funded Alzheimer's Clinical Trial Consortium. These data will serve the scientific community and enable Lilly and other drug developers to enhance our clinical trial designs for other potential medicines targeting Alzheimer's disease."

Launched in 2013, the A4 Study was a first-of-its-kind secondary prevention trial, enrolling more than 1,100 individuals between 65 and 85 years of age who had PET-imaging evidence of amyloid plaque accumulation in the brain and who did not have clinical impairment. Participants were randomized to either solanezumab or placebo and then treated for approximately 4.5 years.

Solanezumab binds only to soluble amyloid-beta protein and was not expected to significantly remove deposited amyloid plaques. Donanemab and remternetug, other Lilly investigational antibodies currently being developed in Phase III, are different from solanezumab in that they specifically target deposited amyloid plaque and have been shown to lead to plaque clearance in treated patients.

The findings indicate that amyloid is a key driver of cognitive decline at the preclinical stage of Alzheimer's disease. Solanezumab did not substantially impact amyloid plaque burden in the brain, and unfortunately did not slow cognitive decline. These data suggest that we may need to be more aggressive with amyloid removal even at this very early stage of disease," said Reisa Sperling, M.D., a neurologist at the Brigham and Women's Hospital, Harvard Medical School and the A4 Study project director. "We are so very grateful to the participants, their study partners, the clinical trial site investigators and staff, and the entire study team for their longstanding dedication to this important study. It is imperative that we learn everything we can to inform ongoing and future trials in our quest to prevent memory loss due to Alzheimer's disease."