Elan, Wyeth Play by Own Rules in Alzheimer's Trial

The paper used a complicated statistical analysis to demonstrate that an alternative cognitive test like the NTB could be just as reliable, perhaps more so, than traditional measures like ADAS-cog.

The paper concludes that the "NTB may represent a useful cognitive measure for clinical trials to assess cognitive change in patients with mild to moderate [Alzheimer's] ... and may be more effective than traditional measures in detecting cognitive changes in the clinical assessment of a therapy designed to reverse or halt disease pathological features."

But the same paper states, "This is the first study to formally evaluate the NTB as a composite measure for [Alzheimer's] clinical trials. Performance on the NTB from other [Alzheimer's] patient samples would provide additional support for the NTB as an alternative cognitive tool."

Five of the six authors of the paper published in the Archives of Neurology are employed by Elan or Wyeth, which paid for the study to be conducted. The sixth author is an outside consultant who works for the companies.

In the phase II study of Elan's AN-1792, patients taking the drug scored worse on the ADAS-cog test than those administered a placebo. It was only using the NTB test that any cognitive benefit was demonstrated with AN-1792, and even then, the improvement was limited.

Whether bapineuzumab can improve the cognitive function of Alzheimer's patients remains an unanswered question. A phase II study of the drug is nearing completion. Analysis of the data from this randomized and controlled study, which enrolled approximately 240 patients with mild to moderate Alzheimer's disease, is expected to begin in April, with results made public in the middle of the year.

It's unusual for drug companies to start pivotal phase III studies without first getting complete data from a phase II study. Elan investors have brushed this anomaly aside and, in some cases, embraced it as a bullish indicator.

That sentiment follows this logic: If bapineuzumab weren't showing a remarkable effect on Alzheimer's patients in the phase II study, Elan and Wyeth would not have taken the risk -- and committed tens of millions of dollars -- to start an ambitious phase III program with 4,000 patients enrolled worldwide.

Most investors expect bapineuzumab to demonstrate any profound effect on cognitive function via an improvement in ADAS-cog scores. But if bapineuzumab follows the path of Elan's past Alzheimer's drug candidates, it may be the NTB, and not ADAS-cog, that picks up any improvement in mental status.

Given the unproven and uncertain nature of the NTB, investors may be in for an unpleasant surprise.