Eli Lilly: EXPEDITION is over but solanezumab should live on

Comtex News Network

Oct 09, 2012 (Datamonitor via COMTEX) --While both EXPEDITION studies missed their primary endpoints, a pooled analysis of solanezumab data has revealed a significant reduction in cognitive decline in mild Alzheimer's disease. The drug's commercial potential in this indication should ensure that Lilly conducts further studies, despite the inherent high risk of failure.

The Alzheimeras Disease Cooperative Study (ADCS) presented detailed, independent analyses of Eli Lillyas two 18-month Phase III trials of solanezumab in mild to moderate Alzheimer's disease patients at the annual meeting of the American Neurological Association in Boston. As previously reported, both studies missed their primary endpoints, even after the statistical analysis plan of EXPEDITION2 was modified to increase its likelihood of success based on the results of EXPEDITION1.

However, solanezumab appeared to be effective on cognition in a subset of patients with mild Alzheimer's disease only. In EXPEDITION1, solanezumab treatment resulted in a 42% reduction in cognitive decline (p=0.008), while drug treatment in EXPEDITION2 yielded a non-significant 20% decline (p=0.120). The difference in functional decline between solanezumab and placebo in both studies was also not significant.

A pooled analysis produced the headline figure of a 34% reduction in cognitive decline (p=0.001) compared with placebo, with a 17% reduction in functional decline just failing to meet significance (p=0.057). Angina and vasogenic edema were both reported in around 1% of solanezumab-treated patients, although no other side effects were found to significantly correlate with drug treatment.

This analysis provides evidence that solanezumab may be an effective treatment for cognition - and possibly even function - in mild Alzheimer's disease. However, optimism should be tempered by the fact that both trials comfortably missed their primary endpoints. Considering that these were registration studies, the effect of drug treatment is likely to be relatively small.

In deciding whether to pursue further expensive clinical studies of solanezumab, Eli Lilly should be cautioned against the sunk cost fallacy. The EXPEDITION is over, as are the prospects of bapineuzumab (Johnson & Johnson/Pfizer), whose head start in the race for first-to-market status forced Eli Lilly to enter Phase III with just 12 weeks of biomarker data. Lilly now has time to consider appropriate further solanezumab studies and judge whether these would provide an appropriate return on investment, given the inherent risk of further failure.

The commercial potential of solanezumab in mild Alzheimer's disease, even if only marginally effective, necessitates further studies. Furthermore, with its nearest potential competitor, Roche's gantenerumab, only at the start of a Phase II/III study, Lilly would have the opportunity to enjoy a disease-modifying monopoly.

Datamonitor currently forecasts solanezumab to achieve sales in excess of $4bn in the seven major markets (the US, Japan, France, Germany, Italy, Spain, and the UK) in 2021.

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