BOSTON—Pooled data from a secondary analysis of two large phase III trials of solanezumab suggest that the drug may modestly slow cognitive loss in patients with mild to moderate Alzheimer’s disease, according to a presentation by Rachelle S. Doody, MD, PhD, at the 2012 Annual Meeting of the American Neurological Association (ANA).
The trials, EXPEDITION 1 and EXPEDITION 2, were conducted by Eli Lilly to study the effects of solanezumab, a humanized anti–amyloid-beta monoclonal antibody that binds to soluble amyloid-beta. In August, Lilly reported that its early analysis of the data indicated that both studies failed to meet their cognitive and functional primary end points.
Further Analysis, New Hope?
The solanezumab analysis presented at the ANA meeting was independently performed by the Data Analysis and Publications Committee of the Alzheimer’s Disease Cooperative Study (ADCS). “As part of our contract with [Lilly], the ADCS receives the raw data from the company, which is really quite unusual, and there are no constraints on our analysis,” said Dr. Doody, Effie Marie Cain Chair in Alzheimer’s Disease Research at the Baylor College of Medicine in Houston.
The two trials involved patients with mild to moderate Alzheimer’s disease, which was defined as a Mini-Mental State Examination score ranging from 16 to 26. A total of 2,052 patients were randomized to receive either placebo or 400 mg of solanezumab every four months for 18 months.
The coprimary end points of EXPEDITION 1 were scores on the Alzheimer’s Disease Assessment Scale Cognition 11 (ADAS Cog 11) and the Alzheimer’s Disease Cooperative Scale–Activities of Daily Living (ADCS–ADL), and these end points were initially chosen as the end points for EXPEDITION 2. With the approval of the FDA, Eli Lilly modified the EXPEDITION 2 end points after the completion of EXPEDITION 1. The primary end point of EXPEDITION 2 was ADAS Cog 14 score in the milder subset of patients.
According to Dr. Doody, the ADCS analysis found similar results to those of Eli Lilly for the specified outcomes. However, the statistical analysis approach of the ADCS analyzed all the outcomes in both trials, as well as a combined analysis of both trials together. They found positive results for both studies in the milder subgroups.
When the researchers examined the combined outcomes of EXPEDITION 1 and 2 in the overall mild and moderate patients, they found a statistically significant difference between the solanezumab and placebo groups on all of the cognitive outcomes. In this combined analysis, there was also a significant effect on the cognitive measures and the activities of daily living measures in the mild subgroup, said Dr. Doody.
Solanezumab May Provide a Small Improvement
“I believe that these data, taken together, suggest that solanezumab slowed cognitive loss, compared to placebo, in mild to moderate patients, and that there was some evidence of a functional benefit in the mild subgroup,” said Dr. Doody.
She added that although the overall effect may be small, may take several months to become apparent, and may be limited to mild patients, “I think there is evidence that targeting amyloid-beta may benefit Alzheimer’s disease patients.”
—Lauren LeBano