"Current approaches for Alzheimer's provide only temporary incremental benefit for patients with Alzheimer's disease," said Christopher Gregory, PhD, vice-president of research, Voyager Pharmaceutical Corporation, Raleigh, North Carolina. "Thus far, our results show that leuprolide acetate together with AChEIs helps women function better on tests of memory and cognition, global function, and the ability to carry out daily routine activities, for nearly a year."

Voyager is investigating the use of leuprolide acetate for the treatment of mild to moderate Alzheimer's disease.

In the phase 2 clinical trial, 109 women who were 65 years of age or older were randomized to treatment with a timed-release, injectable formulation of leuprolide acetate (11.25 mg or 22.5 mg), or placebo, given every 12 weeks for 48 weeks.

Subjects who were on prior AChEI therapy were asked to remain on the same dose of AChEI therapy throughout the trial.

The investigation excluded patients with significant neurologic disease affecting the brain or psychiatric disease other than Alzheimer's disease.

The three treatment groups were similar with respect to baseline demographic and clinical characteristics.

The primary efficacy endpoints were the Alzheimer's Disease Assessment Scale-cognitive (ADAS-cog) and the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC). The ADCS-Activities of Daily Living (ADCS-ADL) was used as a secondary endpoint.

Results of a pre-planned subgroup analysis of 50 women showed that high-dose leuprolide acetate plus AChEI was better than placebo plus AChEI on all efficacy measures.

The mean ADAS-Cog score in the group receiving high-dose leuprolide and an AChEI declined by 0.18 points from baseline at week 48 compared with a mean decline of 3.30 points in the placebo arm (unadjusted, P = .026; adjusted for multiple group comparisons, P = .078).

On the ADCS-CGIC assessment, 58% of the group assigned to high-dose leuprolide and an AChEI was rated as unchanged or improved at week 48 compared with 38% of placebo patients (unadjusted, P = .031; adjusted, P = .093).

The mean ADCS-ADL score in the group treated with high-dose leuprolide and an AChEI declined 0.54 points from baseline at week 48 versus a mean 6.85 point decline in the control group (unadjusted, P = .015; adjusted; P = .044).

Leuprolide was well tolerated.

Leuprolide has been widely used over the past 20 years as a treatment for a range of hormone-related disorders, including prostate cancer, endometriosis, and precocious puberty.

The Alzheimer's Health Assistance Foundation estimates that approximately 350,000 new cases of Alzheimer's disease are diagnosed annually in the U.S. The disease is roughly twice as prevalent in women as in men.

The trial was sponsored by Voyager Pharmaceutical Corporation.


[Presentation title: Stabilization of Cognitive Decline in Alzheimer's Disease Following Treatment with Leuprolide Acetate. Abstract P4-353]

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