Eli Lilly starts second global phase III trial of investigational Alzheimer's disease compound

Eli Lilly and Company today announced it will begin enrolling patients in a second Phase III study of LY450139, a gamma-secretase inhibitor being investigated as a potential treatment to delay the progression of mild to moderate Alzheimer's disease.

The study, called IDENTITY 2, is expected to enroll 1,100 patients from 22 countries. When its results are evaluated along with findings from the first Phase III trial, IDENTITY, a more complete understanding of dosing strategies will be available from a truly global sample of patient data. Because of the study design, IDENTITY 2 will give additional insights into how LY450139 might be dosed in a real-world clinical setting. Patients or caregivers interested in learning more about how to enroll in either IDENTITY study are encouraged to visit www.lillytrials.com or call 1-877-CTLilly (1-877-285-4559).

While the precise cause of Alzheimer's disease is not known, current theory is that subtypes of amyloid beta, a type of sticky protein, clump together and eventually kill brain cells, causing the symptoms of the disease. LY450139 is a once-daily oral agent that is believed to slow the progression of Alzheimer's disease by inhibiting gamma secretase, an enzyme that can create amyloid beta. By blocking gamma secretase, there is less amyloid beta formed and potentially less brain cell death.

"We are proud to begin a second global trial of our gamma-secretase inhibitor in patients suffering from the devastating effects of Alzheimer's disease," said Eric Siemers, M.D., medical director, Alzheimer's disease research for Eli Lilly and Company. "IDENTITY 2 is a study that we believe will give us additional insights into how LY450139 might best be given to patients in real clinical situations, information that is often not learned until a medicine is approved and prescribed in clinical practice. The start of this key trial is an important landmark for Lilly, especially considering the ongoing IDENTITY study, and the planned initiation of a Phase III study of our other investigational treatment for Alzheimer's disease, an anti-amyloid beta monoclonal antibody, next year. Lilly has a strong commitment to Alzheimer's disease -- we have an extensive early research program and are the only pharmaceutical company with two of its own Alzheimer's disease molecules in active late-stage development."

IDENTITY 2 - Interrupting Alzheimer's Dementia by EvaluatiNg Treatment of AmyloId PaThologY

IDENTITY 2 is expected to enroll 1,100 patients, and includes a treatment period of approximately 21 months. An open-label extension will be available to all participants completing the study. In IDENTITY 2, patients will be randomized to receive either 140 mg of LY450139 or placebo. Patients who are taking currently available symptomatic treatments for Alzheimer's disease can continue treatment during their participation in IDENTITY 2. The study also incorporates a "randomized delayed start" design, which means that even those subjects initially assigned to the placebo arm will be started on LY450139 sometime before the end of the 21-month study period. Also, because investigators have the flexibility to lower and then increase the dose based on patient tolerability, IDENTITY 2 is designed to provide a more real-world simulation of how LY450139 could be used in clinical practice.

The primary endpoints for IDENTITY 2 are the same co-primary endpoints as the IDENTITY trial: Alzheimer's Disease Assessment Scale-Cognition (ADAS-cog), which measures cognitive function with an emphasis on memory, and the Alzheimer's Disease Cooperative Study - Activities of Daily Living scale (ADCS-ADL), which measures the ability to independently perform daily activities such as eating, bathing, and using the telephone. A number of optional biomarker substudies will be available to patients that will utilize brain-scanning and biochemical techniques to detect markers of Alzheimer's disease.

Alzheimer's disease is a progressive neurodegenerative condition that is the most common cause of dementia, accounting for 60 to 80 percent of cases. Estimates show that 6-8 percent of people over age 65 are affected by Alzheimer's disease, totaling approximately 5.5 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 and other dementias in the U.S. are estimated to be about $150 billion. In 2005, the total cost worldwide of dementia, of which Alzheimer's disease is the most common cause, was estimated at $315.4 billion. 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.

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 and eventually kill 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.