In the early 2000s, researchers from Washington University in St. Louis and drugmaker Eli Lilly began testing an experimental drug, solanezumab, in mice, aiming to disable a protein believed to be the root cause of Alzheimer’s disease. After nearly two decades of research and multiple Phase 3 trials, Lilly has conceded defeat for solanezumab. The final study, known as the A4 study, which began in 2013 and involved over 1,100 older adults across the U.S., Canada, Australia, and Japan, showed that solanezumab failed to slow cognitive decline in individuals whose brains harbored the suspect protein but had not yet shown clinical signs of Alzheimer’s.
John Sims, Lilly’s head of the drug’s medical and global brand development, stated that the A4 study clearly showed that the primary and secondary endpoints were not met, concluding the clinical development of solanezumab. This announcement marks the end of Lilly’s efforts to develop solanezumab into a blockbuster medicine for Alzheimer’s, despite the drug once being the prize of Lilly’s pipeline.
Lilly’s journey with solanezumab included enrolling thousands of people in multiple Phase 3 trials, comparing the drug to a placebo, with the hope that removing amyloid from the blood could treat Alzheimer’s. Despite initial failures in 2012 and a subsequent large Phase 3 trial in 2016, Lilly continued its research, leading to another investigator-led study that came up short in 2020. These trials suggested that targeting insoluble amyloid in the blood might be necessary and raised questions about the sufficiency of reducing amyloid brain accumulation for treating Alzheimer’s.
Despite the setbacks with solanezumab, Lilly remains committed to Alzheimer’s research, developing other drugs like donanemab and remternetug, which target amyloid in different ways. Lilly believes that the failure of solanezumab does not diminish the prospects of these new drugs, as they specifically target deposited amyloid plaque and have shown to lead to plaque clearance in treated patients. However, Lilly now trails behind rivals Eisai and Biogen, which have already secured FDA approval for their amyloid-targeting drug, Leqembi.
The pharmaceutical industry continues to face skepticism from insurers and physicians regarding Alzheimer’s treatments, as seen with Biogen’s Aduhelm, which secured accelerated FDA approval in 2021 but failed to gain payer support. This has prompted companies like Eisai, Biogen, and Lilly to focus on securing full FDA approvals to better establish their drugs in the market.
