Another AD Drug Disappoints (Although Placebo Looks Promising)

A novel, experimental molecule, AZD3480, did not significantly change cognition (per the ADAS-cog) at 12 weeks in a randomized, placebo-controlled, dose-finding study of 567 European or Canadian patients with mild-moderate Alzheimer's disease. Early results of the phase 2b study were revealed Monday by the molecule's codevelopers, Targacept and AstraZeneca.

In addition, the approved AD drug donepezil (Aricept; Eisai/Pfizer) did not significantly change the mean ADAS-cog score at 12 weeks. (The dosage of donepezil studied was not provided in the companies' press release.) Disappointing outcomes with AZD3480, a selective agonist of a neuronal nicotinic receptor subtype (α4β2), and donepezil, an AChE inhibitor, were due to unexpected cognitive improvement in those patients who received placebo, wrote the companies.

Patients who received 2 of 3 tested doses of AZD3480 did show modest cognitive improvement per secondary outcome measures, as did patients who received donepezil. AZD3480 appeared to be better tolerated than donepezil, with fewer episodes of diarrhea, nausea, or vomiting.

The companies indicate that analysis of the trial results is ongoing, and trial data will be presented in a scientific setting at some unspecified time and place. A decision regarding the continued development of the AD drug candidate is expected at the end of this calendar year. AZD3480 is also being evaluated for the treatment of cognitive dysfunction in schizophrenia (trial results are expected at the end of 2008) and adult attention deficit/hyperactivity disorder.

AChE = acetylcholinesterase; ADAS-cog = Alzheimer's Disease Assessment Scale-cognitive subscale.

Photograph: Atrophied brain from person with AD from National Institute on Alcohol Abuse and Alcoholism.