From the International Conference on Alzheimer’s Disease
MADRID—Patients with mild-to-moderate Alzheimer’s disease (AD) who receive leuprolide acetate (Lupron) as an adjunct to standard acetylcholinesterase inhibitor (AChEI) therapy appear to maintain cognitive and physical functioning longer than those treated with AChEIs alone, based on a phase 2 study presented at the International Conference on Alzheimer’s Disease and Related Disorders.
Leuprolide acetate is an anti-gonadotropic agent that has been safely used for 20 years to treat hormone-related disorders, such as prostate cancer, endometriosis, and precocious puberty. Voyager Pharmaceutical Corporation, Raleigh, NC, is testing a biodegradable, polymeric implant that provides a sustained-release formulation of leuprolide.
“Thus far, our results show that leuprolide acetate, together with AChEIs, helps women function better than AChEIs as solo therapy on tests of memory and cognition, global function, and the ability to carry out daily routine activities for nearly a year,” said Christopher Gregory, PhD, vice-president of research at Voyager.
AChEIs are currently the only drugs approved by the FDA for the treatment of mild-to-moderate AD.
“Increased levels of luteinizing hormone have been shown to be associated with the risk factors and multiple pathologies characteristic of Alzheimer’s disease,” Dr Gregory pointed out. “We believe that decreasing luteinizing hormone levels in Alzheimer’s disease patients with leuprolide acetate may postpone the progression of Alzheimer’s disease by arresting some of the pathological processes in the brain that are linked to the development of Alzheimer’s disease.”
In this phase 2 trial, 109 women aged ≥65 years were randomized to a timed-release, injectable formulation of leuprolide (11.25 or 22.5 mg) or placebo, given every 12 weeks for 48 weeks. Patients were instructed to continue AChEI therapy.
The primary end points were changes from baseline scores on standard AD cognitive tests. The change from baseline score in Alzheimer’s Disease Cooperative Study-Activities of Daily Living was a secondary efficacy measure.
Preplanned subgroup analysis of 50 women showed improved cognitive functioning at 48 weeks’ follow-up in the high-dose leuprolide group compared with the placebo group. The treatment was well tolerated.
“The limitations of current therapies are that they are palliative only—they reduce the symptoms of the disease temporarily, but eventually the disease will continue to progress to the point that the drugs will no longer be beneficial,” said Kathleen Toups, MD, medical director at the Bay Area Research Institute in Lafayette, Calif, and an investigator in a phase 2 men’s study and ongoing phase 3 trials of leuprolide.?
“The difference with leuprolide is that it actually appears to have a disease-modifying effect, theorized to be due to?blocking luteinizing hormone from causing destruction of neurons in the brain. Interrupting the disease at this level is thought to prevent the downstream effects of amyloid plaques and neurofibrillary tangles that occur from neuron destruction and which are the hallmark characteristics of Alzheimer’s disease.”
An estimated 4.5 million people in the United States have AD. Annual costs are expected to account for 40% ($100 billion) of Medicare costs by 2050.