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Leuprolide Acetate Maintains Functional Capabilities In Women With Alzheimer's Disease

May 16, 2017

MADRID - Women with mild to moderate Alzheimer's disease who are treated with the investigational hormone drug leuprolide acetate and conventional therapy with acetylcholinesterase inhibitors (AChEI) seem to maintain their cognitive and physical function longer than women treated with AChEI therapy alone, according to phase II results released at the Tenth International Conference on Alzheimer's Disease and Related Disorders (ICAD).

Leuprolide acetate, which is commonly used in the treatment of prostate cancer and other hormone-related diseases, suppresses the synthesis and release of luteinizing hormone. Increased levels of luteinizing hormone have been shown to be associated with the risk factors and multiple pathologies characteristic of Alzheimer's disease. Voyager Pharmaceutical Corporation in Raleigh, North Carolina, is investigating the use of leuprolide acetate for the treatment of mild to moderate Alzheimer's disease.

For the trial, 109 women with mild to moderate Alzheimer's disease who were 65 years of age or older were randomized to treatment with a timed-release, injectable formulation of leuprolide or placebo. Treatment was administered every 12 weeks for 48 weeks.

"Leuprolide acetate has been used safely for more than twenty years in the treatment of other diseases," Chris Gregory, Ph.D., Voyager's vice president of research, said. "Our scientific hypothesis for these clinical trials was that lowering luteinizing hormone levels in Alzheimer's disease patients with leuprolide acetate may slow the progression of Alzheimer's disease by arresting some of the pathological processes occurring in the brain."

At enrollment, all subjects had a Mini-Mental State Examination (MMSE) score of 12 to 24.

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

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 Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) was used as a secondary efficacy measure.

Results of a pre-planned subgroup analysis of the 50 women on AChEI therapy showed that the active treatment group (22.5 mg leuprolide plus AChEI) performed better than the control group (placebo plus AChEI) on all efficacy measures.

The mean ADAS-cog score in the active treatment group (22.5 mg leuprolide acetate plus AChEI) declined by 0.18 points from baseline at week 48 compared to a mean decline of 3.30 points in the placebo group.

Fifty-eight percent of the active treatment group was rated as unchanged or improved on the ADCS-CGIC assessment compared with 38 percent of the placebo group at week 48.

The mean ADCS-ADL score in the active treatment group declined 0.54 points from baseline at week 48 versus a mean 6.85 point decline in the control group.

Leuprolide was well tolerated.

All women in the phase II trial were eligible to participate in an open-label extension study. Nearly 90 percent chose to continue in the extension study. All 13 women who have been followed for an additional 48 weeks in the extension study have continued to show benefit.

"Our results suggest that leuprolide acetate plus AChEI treatment results in better performance on important cognitive and behavioral measures, compared to treatment with AChEIs alone, and AChEIs are presently the most commonly prescribed therapy for Alzheimer's," Dr. Gregory said.

Approximately 18 million people worldwide have Alzheimer's disease, including 4.5 million Americans.

The study, which was conducted at five U.S. sites, was sponsored by Voyager Pharmaceutical Corporation, www.voyagerpharma.

By Jill Stein
Jill Stein is a Paris-based freelance medical writer.