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Next Steps for Solanezumab, Potential Alzheimer’s Drug

Company decides to withhold FDA application (Dec. 12)

Eli Lilly and Company has provided an update on the next steps planned for solanezumab, its phase III monoclonal antibody being studied as a potential therapy for patients with mild Alzheimer's disease (AD). Following discussions with regulators in the U.S., Canada, and Europe, the company has announced that it plans to conduct an additional phase III trial of solanezumab in patients with mild AD. The new study is expected to be initiated no later than the third quarter of 2013.

Based on recent meetings with the FDA, the company does not intend to submit a Biologics License Application (BLA) at this time in the U.S. based solely on the existing analyses of data from the EXPEDITION studies.

Solanezumab is a monoclonal antibody that binds to soluble monomeric forms of amyloid-beta, allowing the amyloid to be cleared before it clumps together to form beta-amyloid plaques.

The EXPEDITION trials were two phase III, double-blind, placebo-controlled studies of solanezumab in patients with mild-to-moderate AD. In both protocols, mild AD was defined as a baseline Mini-Mental Status Examination (MMSE) score of 20 to 26, and moderate AD was defined as a baseline MMSE score of 16 to 19.

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

The primary efficacy endpoints — both cognitive and functional — were not met in either EXPEDITION trial. However, a prespecified secondary analysis of pooled data in patients with mild AD showed a statistically significant slowing of cognitive decline. This finding represented a 34% reduction in decline.

In pooled analyses of the two 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 incidence of vasogenic edema was approximately 1%, occurring in 11 patients treated with solanezumab and in five patients given placebo, which was not statistically significant.

An open-label extension study, EXPEDITION-EXT, is ongoing.

Source: Eli Lilly; December 12, 2012.

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