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Mixed Phase III Results for Solanezumab in Alzheimer’s Disease

Cognitive decline slowed versus placebo (Oct. 8)

On October 8, Eli Lilly and Company announced the results from its phase III, double-blind, placebo-controlled EXPEDITION studies of solanezumab, a monocloncal antibody, in patients with mild-to-moderate Alzheimer's disease (AD). This announcement followed the presentation of results from independent analyses of the EXPEDITION study data conducted by the Alzheimer's Disease Cooperative Study (ADCS), an academic research consortium, at the annual meeting of the American Neurological Association (ANA).

Lilly provided the full data set collected from the EXPEDITION studies to the ADCS. The ADCS statisticians then performed independent analyses of the information.

The EXPEDITION-1 trial was designed with co-primary cognitive and functional endpoints — the Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-Cog11) and the Alzheimer's Disease Cooperative Study–Activities of Daily Living (ADCS-ADL), respectively — in patients with mild-to-moderate AD.

Lilly's prespecified secondary analyses showed that results in patients with mild AD taking solanezumab demonstrated a slowing of cognitive decline compared with placebo (P = 0.008), as measured by the ADAS-Cog11. This finding represented a 42% reduction in decline at the end of the 18-month study. The difference in functional decline (ADCS-ADL) was not statistically significant.

Based on the results of EXPEDITION-1 study, Lilly modified the statistical analysis plan for EXPEDITION-2 to specify a single primary endpoint of cognition in patients with mild AD, as measured by the ADAS-Cog14, a 14-item scale that includes three additional items considered relevant for patients with mild AD.

At the conclusion of EXPEDITION-2, there was a 20% reduction in cognitive decline in patients with mild AD taking solanezumab; however, the treatment difference versus placebo was not statistically significant (P = 0.120). In the prespecified secondary endpoint of ADCS-ADL, there was a 19% reduction in functional decline in patients with mild AD treated with solanezumab compared with placebo; again, this difference was not statistically significant (P = 0.076).

A secondary analysis of pooled data in patients with mild AD from both studies showed a slowing of cognitive decline (P = 0.001) compared with placebo, as measured by the ADAS-Cog14; this finding represented a 34% reduction in decline. In addition, the secondary analysis of the pooled data showed a 17% reduction in functional decline, as measured by the ADCS-ADL; however, the treatment difference was not statistically significant compared with placebo (P = 0.057).

In the EXPEDITION studies, the only adverse event with an incidence of at least 1% that occurred significantly more often in the solanezumab group than in the placebo group was angina (1.1% vs. 0.2%, respectively).

The designs of EXPEDITION-1 and EXPEDITION-2 were the same. Patients aged 55 to 94 years were eligible to participate in the studies; EXPEDITION-1 enrolled 1,012 patients, and EXPEDITION-2 enrolled 1,040 patients. The patients received either 400 mg of solanezumab infused intravenously or placebo every 4 weeks for approximately 18 months. Both EXPEDITION trials allowed patients to remain on stable standard of care (defined as their existing treatment regimen). More than 85% of the patients in these trials were taking an acetycholinesterase inhibitor and/or memantine.

For more information, visit the Eli Lilly Web site.

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