Eli Lilly and Company has started a phase III clinical trial studying LY450139, an investigational gamma secretase inhibitor for the treatment of mild to moderate Alzheimer's disease. LY450139 is being tested to see if it can slow the progression associated with Alzheimer's disease by inhibiting gamma-secretase, an enzyme that can create a sticky protein called amyloid beta. Current Alzheimer's disease theory is that subtypes of amyloid beta clump together into plaques that eventually kill off brain cells. By blocking gamma secretase, there is less amyloid beta formed, potentially slowing brain-cell death.
Slowing the rate of disease progression could preserve independent functioning and quality of life for Alzheimer's patients in the milder stages of the disease, potentially delaying the onset of the severe stages of the disease. Currently available treatments for Alzheimer's disease have no documented effect on amyloid beta. They provide modest improvements in symptoms but do not slow the underlying disease process.
IDENTITY (Interrupting Alzheimer's Dementia by EvaluatiNg Treatment of AmyloId PaThologY) is a randomised, double-blind, placebo-controlled trial that would be conducted in the US and 21 additional countries. As part of IDENTITY, 1,500 patients will be studied for 21 months, and an open-label extension will be available to all participants completing the study. Patients who are taking currently available symptomatic treatments for Alzheimer's disease can continue treatment during their participation in IDENTITY. Because the IDENTITY study also incorporates a "randomised delayed start" design, even those subjects initially assigned to the placebo arm of the study will be started on active LY450139 treatment sometime before the end of the 21-month study period. Both the subjects and investigators will be blinded to the exact timing of this delayed start of study drug administration.
"Alzheimer's is a devastating disease that destroys brain cells, affecting everything from a patient's memory to their work and social life. Currently available medications treat the symptoms of Alzheimer's disease but have not been shown to change its underlying progression, creating an urgent unmet medical need. Today, we are proud to announce the start of the IDENTITY clinical trial and hold hope that LY450139 will represent an advance in the attempt to slow the progression of this fatal disease. We encourage patients or their caregivers to review the enrollment criteria for IDENTITY to see if they are eligible to participate," said Eric Siemers M.D., medical director, Alzheimer's disease research, Eli Lilly and Company.
Alzheimer's disease is a progressive neurodegenerative condition that is the most common cause of dementia in patients over 65 years of age. Estimates show that 6-8 per cent of people over age 65 are affected by Alzheimer's disease, totalling approximately 5 million people in the United States alone. Every 72 seconds, an American is developing Alzheimer's disease, and it is the seventh-leading cause of death in the United States. The direct and indirect health care costs associated with Alzheimer's disease in the US are estimated to be about $150 billion. In 2005, the total cost worldwide was estimated at $315.4 billion.
To more completely characterise the disease-modifying effects of LY450139, a number of optional biomarker sub-studies will be available to patients. These optional sub-studies will utilize new brain-scanning techniques to determine the amount of amyloid beta plaque in the brain, employ other, more established scanning techniques to examine brain structure and function, and evaluate a number of additional biochemical measures of Alzheimer's disease. By determining the effect of LY450139 on these objective biomarkers, a more complete understanding of the effect of LY450139 on underlying Alzheimer's disease pathology is possible.
LY450139 inhibits gamma secretase, an enzyme that cuts a protein, creating a shorter, sticky protein called amyloid beta. Alzheimer's disease theory suggests that some subtypes of amyloid beta clump together into plaques that eventually kill off brain cells. Clinical studies have examined the effect of LY450139 on amyloid beta in blood and cerebrospinal fluid. The most frequently occurring side effects experienced in earlier clinical studies with LY450139 include diarrhoea, upset stomach, and fatigue.
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Dec 2009 - Bad effects in animals can indicate possible risks to humans. A higher rate of cancer of the ovaries and cancer of the uterus was seen in old animals that were given LY450139 every day from the time they were young compared with animals not given LY450139. The effect on ovaries was likely ralted to the effect of LY450139 on young, active ovaries. The effect on the uterus might also be related to the effects on ovaries and changes in hormones that might occur because of that. hile the relevance to humans is not completely understood, human females taking LY450139 must be post menipausal (i.e. have no menstrual periods for at least 12 months in a row or have had both ovaries removed), so their ovaries will no longer be active when they start taking LY450139. Including only post menpausal women is likely to reduce the risk. Ovarian or uterine cancer has not been reported with LY450139 in any of the human studies done so far.
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