Elan, Wyeth Bury Missed Primary Endpoints in Phase 2 Trial of AD Drug

Elan and Wyeth announced "encouraging top-line results" from a randomized, dose-ranging phase 2 trial of bapineuzumab in 240 patients with mild-to-moderate Alzheimer's disease; although the monoclonal antibody was no better than placebo when assessing cognition or disability at 18 months, the primary endpoints. A press release from the companies contained the primary-endpoint data in the second paragraph.

Instead the companies chose to highlight results from the post-hoc analyses of subgroups, including patients who do not carry the high-risk apolipoprotein E4 allele (40%-70% of AD patients).* Data in this subgroup showed "statistically significant and clinically meaningful benefits" with bapineuzumab, per cognitive scales like the ADAS-cog. The treated subgroup also demonstrated relatively preserved brain volume on MRI, the press release reported.

Safety data in the phase 2 trial indicated that ApoE4 carriers may be especially prone to vasogenic edema with the agent. Consequently the dose of bapineuzumab, an anti-Aβ agent, is being modified for this subpopulation in phase 3 studies. According to ClinicalTrials.gov, two phase 3 studies of bapineuzumab in AD are currently recruiting subjects, and another two phase 3 studies are "active" but "not yet recruiting."

The Elan/Wyeth press release indicates that full details of the phase 2 study will be presented July 28 at the International Conference on Alzheimer's Disease in Chicago. Despite the mixed phase 2 results, the reaction of Wall Street was mostly optimistic, according to the WSJ Health Blog.

06/18/08 update: According to Forbes, analysts Leerink Swann and Davy Stockbrokers are talking up the study and the companies' prospects. For no particularly good reason, respective share prices of Elan and Wyeth shot up yesterday 10.6% and 4.8%.

Image: depiction of amyloid plaque from National Institute on Aging.

Aβ = amyloid beta.

*So, in this case, we may guess that approximately 12-20 patients per treatment group (4 for bapineuzumab; 4 for placebo) were noncarriers.