Lilly’s New Alzheimer’s Drug Suffers Setback as Phase 3 Results Fall Short of Expectations

Eli Lilly and Company (Lilly) recently announced the latest results of the Phase 3 Anti-Amyloid Treatment in Asymptomatic Alzheimer’s disease (A4) Study regarding solanezumab, the company’s investigational anti-amyloid antibody. Despite Lilly’s high expectations for the new drug, clinical trial results clearly indicated that the primary and secondary endpoints were not met.

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Antibody Targeting Soluble Amyloid-beta Peptides

In the United States, more than 6.5 million people suffer from dementia due to Alzheimer’s disease, and scientists anticipate that the number will nearly triple by 2050. Besides, it is estimated that over 20 million Americans and approximately 315 million people worldwide have preclinical Alzheimer’s disease, the earliest stage of the disease. 

According to the amyloid hypothesis, the accumulation and deposition of amyloid-beta (Aβ) peptides play a key role in the pathogenesis of Alzheimer’s disease. In particular, individuals at the preclinical stage of the disease have an elevated level of amyloid plaque in their brain which can be shown by PET amyloid imaging. Although they have not yet been clinically impaired, they are at a high risk of cognitive decline in the future.

Lilly’s solanezumab is a humanized monoclonal antibody which is designed to increase clearance from the brain of soluble Aβ. In 2013, the company launched the A4 Study to determine if solanezumab could slow the cognitive decline associated with the disease, as well as if anti-amyloid therapy could delay the progression of Alzheimer’s-related brain injury via imaging and other biomarkers over a period of approximately 4.5 years. The study recruited approximately 1,100 participants between 65 and 85 years of age.

Pathological and Cognitive Examination Proves Failure of Solanezumab

Based on the latest results released by Lilly, solanezumab did not slow the cognitive decline associated with Alzheimer’s disease on the primary outcome measure, while the secondary outcome results were also consistent with the primary outcome, in a way that solanezumab failed to show any significant clinical advantages over the placebo. 

With the assessment using Clinical Dementia Rating-Global Scale, it was found that the percentage of participants showing disease progression in the solanezumab group was similar to that in the placebo group. Also, on amyloid PET imaging, amyloid continued to accumulate over time in both the solanezumab and placebo groups.

“These findings indicate that amyloid is a key driver of cognitive decline at the preclinical stage of Alzheimer’s disease. Solanezumab did not substantially impact the 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., the A4 Study project director.

Author

Richard Chau