Eli Lilly and Co has started a Phase III Clinical Trial of LY450139, an investigational gamma secretase inhibitor for the treatment of patients with mild/moderate Alzheimer’s disease. The trial aims to see whether it can slow the progression associated with Alzheimer’s by inhibiting gamma-secretase. Gamma-secretase is an enzyme that can create amyloid beta – a sticky protein.

The current theory goes that subtypes of amyloid beta stick together and form plaques – these plaques play a key role in killing off brain cells. If the gamma secretase can be blocked less amyloid beta is formed, and subsequently plaques are formed and fewer brains cells are killed off.

Patients whose Alzheimer’s progression is slowed down may be able to preserve independent functioning and quality of life in the milder disease stages. Also, it is hoped that LY450139 may delay the onset of the severe stages of Alzheimer’s.

To date, there are no Alzheimer’s disease treatments which have a documented effect on amyloid beta. At best, current treatment may provide modest improvements in symptoms, but have no impact on slowing down the underlying disease process.

The IDENTITY Trial
Interrupting Alzheimer’s Dementia by EvaluatiNg Treatment of AmyloId PaThologY

IDENTITY is a randomized, double-blind, placebo-controlled trial that will be carried in the United States and 21 other countries. As part of IDENTITY, 1,500 patients will be monitored for 21 months, and an open-label extension will be available to all participating patients who complete the study.

Participants who are taking currently available symptomatic treatments for Alzheimer’s disease may continue treatment during their participation in IDENTITY. As the IDENTITY study also incorporates a “randomized 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.

Eric Siemers M.D., Medical Director, Alzheimer’s disease research for Eli Lilly and Company, said “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.”

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% of people over age 65 are affected by Alzheimer’s disease, totaling 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 U.S. are estimated to be about $150 billion. The total cost globally in 2005 was estimated at $315.4 billion.

As life-expectancy grows, without the availability of medicines that delay or prevent the onset of Alzheimer’s disease, the number of affected people is expected to at least triple by the year 2050 in developed nations. The average duration between onset of symptoms and death due to complications of Alzheimer’s disease is about 8-10 years. The burden to caregivers and health care costs can increase dramatically in the late stages of Alzheimer’s disease, when patients cannot maintain independent function and are frequently bedridden.

To more completely characterize 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.

For further information about the IDENTITY trial, including global recruitment sites, visit www.clinicaltrials.gov or www.lillytrials.com or by call 1-877-CTLilly (1-877-285-4559).

About LY450139

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 diarrhea, upset stomach, and fatigue. For a more complete listing of potential side effects, prospective clinical trial participants should refer to the informed consent document.

www.lilly.com

Written by – Christian Nordqvist