Eli Lilly and Company (NYSE: LLY) today announced that the primary endpoints, both cognitive and functional, were not met in either of the two Phase 3, double-blind, placebo-controlled solanezumab EXPEDITION trials in patients with mild-to-moderate Alzheimer’s disease.
However, a pre-specified secondary analysis of pooled data across both trials showed statistically significant slowing of cognitive decline in the overall study population of patients with mild-to-moderate Alzheimer’s disease. In addition, pre-specified secondary subgroup analyses of pooled data across both studies showed a statistically significant slowing of cognitive decline in patients with mild Alzheimer’s disease, but not in patients with moderate Alzheimer’s disease.
Adverse events with an incidence of at least 1 percent that occurred statistically significantly more in the solanezumab group than in the placebo group were lethargy, rash and malaise (in EXPEDITION1) and angina (in EXPEDITION2).
An ongoing, open-label extension study, EXPEDITION-EXT, is fully enrolled and will continue as planned.
“We recognize that the solanezumab studies did not meet their primary endpoints, but we are encouraged by the pooled data that appear to show a slowing of cognitive decline,” said John C. Lechleiter, Ph.D., chairman, president and chief executive officer, Lilly. “We intend to discuss these data with regulatory authorities to gain their insights on potential next steps.”
“Lilly is committed to finding medicines that alter the underlying pathology of Alzheimer’s disease for the benefit of patients and their loved ones,” said Jan Lundberg, Ph.D., executive vice president, science and technology, and president, Lilly Research Laboratories. “We believe the pooled data support the amyloid hypothesis, as these are the first Phase 3 data with an anti-beta amyloid agent that appear to show a slowing of cognitive decline.”
An independent analysis of the data from the EXPEDITION studies is being performed by the Alzheimer’s Disease Cooperative Study (ADCS), an academic national research consortium that facilitates the discovery, development and testing of new drugs for the treatment of Alzheimer’s disease. ADCS will present their findings at the American Neurological Association (ANA) meeting in Boston, Mass., on October 8, 2012, and at the Clinical Trials on Alzheimer’s Disease (CTAD) meeting in Monte Carlo, Monaco, on October 30, 2012.
The next steps for solanezumab have not yet been decided and will be determined after discussions with regulators.
About the clinical trial endpoints for the EXPEDITION studies
The EXPEDITION1 study did not meet co-primary cognitive and functional endpoints in the overall mild-to-moderate patient population; however, pre-specified secondary subgroup analyses in patients with mild Alzheimer’s disease showed a statistically significant reduction in cognitive decline. Based on those results, Lilly modified the statistical analysis plan (SAP) for EXPEDITION2 prior to database lock to specify a single primary endpoint of cognition in the mild patient population. This revised primary endpoint did not achieve statistical significance. In both of the EXPEDITION study protocols, mild Alzheimer’s disease was defined as a baseline Mini-Mental Status Examination (MMSE) score of 20 to 26 and moderate Alzheimer’s disease was defined as a baseline MMSE score of 16 to 19.