Macro Tsimmis

intelligently hedged investment

Élan (ELN) update #9

Posted by intelledgement on Thu, 28 Feb 08

An Adam Feuerstein article published yesterday by TheStreet.com has raised questions about the criteria our premier biotech company, Élan (ELN) and their partner Wyeth (WYE) are employing in their ongoing Phase 3 trial of their Alzheimer’s Disease (AD) candidate drug AAB-001 (bapineuzumab). The companies have apparently asked the FDA to approve an alternative to ADAS-cog, the measure of cognitive function which has been used as the basis for approval for all Alzheimer’s disease drugs to date. This alternative measure, which has been designed by researchers working for Élan, is called Neuropsychological Test Battery, or NTB.

According to an article published in Volume 12 of “Research and Practice in Alzheimer’s Disease” last year, “it is agreed generally that the ADAS is an imperfect instrument and remains so despite efforts to correct its deficiencies…. [T]he ADAS-cog lacks appropriate measures of key cognitive skills and in particular attention, working memory and executive function.” The author of the article, J. E. Harrison—who consulted with Élan on the development of NTB—recounts that ADAS-cog dates from the early days of AD research, when the effects of the disease were not as well understood. So coming up with new criteria for measuring the efficacy of new AD drugs is a good idea.

Feuerstein points out, however, that having the folks developing one of those drugs also designing the new criteria is an apparent conflict of interest. As it happens, in a Phase 2 trial of an earlier Élan AD drug, AN-1792, patients taking the drug scored worse on the ADAS-cog test than those who received a placebo. When those patients were given the NTB test, the results demonstrated a cognitive benefit. (AN-1792 was subsequently shelved when toxicity issues developed.)

Although the issue must have been decided, the companies have not yet publicly announced the primary endpoint of the AAB-001 Phase 3 study, which aims to enroll 4000 patients. It is unimaginable that the FDA would sanction the launch of a Phase 3 study without the primary endpoint having been defined. It will be interesting to see if the FDA has agreed to let Élan and Wyeth use NTB test results as the primary end point (and relegate the old war horse ADAS-cog to being the secondary end point).

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