Myriad Genetics Completes Enrollment in Second Phase 3 Clinical Trial of Flurizan(TM) in Alzheimer's Disease
- Category: Small Molecules
- Published on Wednesday, 21 March 2007 02:00
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SALT LAKE CITY, UT, USA | Mar 20, 2007 | Myriad Genetics, Inc. (NASDAQ: MYGN) (www.myriad.com) announced today that it has completed enrollment of patients in its global Phase 3 clinical trial of Flurizan(TM) (tarenflurbil) in Alzheimer's disease.
The global Phase 3 clinical trial, ActEarliAD, is a multinational, randomized, double-blind, placebo-controlled study of Flurizan in over 800 patients with mild Alzheimer's disease, who will be followed for 18 months. Patients enrolled in the study take 800 mg twice daily of either Flurizan or placebo and attend periodic physician visits for analysis of their performance on memory, cognition and behavioral tests. The two primary clinical endpoints of the trial are the change in cognitive decline and function, as measured by the Alzheimer's Disease Assessment Scale -- cognitive subscale (ADAS-cog) and changes in activities of daily living, as measured by the Alzheimer's Disease Cooperative Study -- Activities of Daily Living inventory (ADCS-ADL). A secondary endpoint of the trial is the change in overall function, measured by the Clinical Dementia Rating -- sum of boxes (CDR-sb) test. Additional exploratory outcome measures are designed to assess the psychological, physical and financial impact of this disease on caregivers and medical resources. The trial is designed to meet the requirements of the European Agency for the Evaluation of Medicinal Products, or EMEA, for marketing approval of Flurizan in Europe.
The primary endpoints in the global trial are identical to those of the U.S. Phase 3 trial and are the same as two of the three endpoints in the Phase 2 study. As was the case with the Phase 2 study, all patients in the Phase 3 studies are permitted to take current standard of care medicines in addition to Flurizan or placebo, provided their dose has been stable for six months. Therefore, benefits seen in the trials are in addition to any benefit provided by the current standard of care drugs. Myriad announced the completion of enrollment in the U.S. Phase 3 trial in August 2006.
Myriad conducted a double-blinded, placebo-controlled Phase 2 trial of Flurizan for 12 months duration in 207 patients with mild to moderate Alzheimer's disease. The study enrolled patients in the United Kingdom and Canada. After 12 months, patients with mild Alzheimer's disease in Canada were eligible to enroll in an additional double-blinded 12-month treatment study. The results of this study were presented in July 2006 at the 10th International Conference on Alzheimer's Disease and Related Disorders, in Madrid, Spain. Additional results were presented earlier this month at the American Association for Geriatric Psychiatry in New Orleans, Louisiana.
Highlights of the Phase 2 Flurizan study include:
1. CDR-sb. A semi-structured interview with both the patient and caregiver, it is an overall (global) functional measure of Alzheimer's disease. A patient's performance is assessed in memory, orientation, judgment, problem solving, community activities, home and hobbies and personal care. Mild patients on 800 mg twice daily Flurizan showed a 72% reduced rate of decline (p=0.0005) at 24 months versus the placebo patient rate of decline over the first 12 months.
2. ADCS-ADL. A test completed by the patient's caregiver, it is a measure of the patient's ability to perform basic activities of daily living, such as dressing, eating, bathing and traveling. Mild patients on 800 mg twice daily Flurizan had a 67% (p=0.015) reduced rate of decline at 24 months in their ability to perform these activities, versus the placebo patient rate of decline over the first 12 months.
3. ADAS-cog. A test completed by the patient, it is a measure of a patient's performance in word recall, response to directions, ability to copy geometric forms, delayed word recall, ability to name objects, memory and quality of speech. It is the primary measure of memory and understanding used by regulatory authorities. Mild patients on 800 mg twice daily Flurizan showed a 52% (p=0.109) reduced rate of decline in these areas, versus the placebo patient rate of decline over the first 12 months.
4. MMSE. A test completed by the patient and administered by the physician, it is the standard clinical measure used by practicing physicians to assess, diagnose and monitor patients with Alzheimer's disease. Mild patients on 800 mg twice daily Flurizan showed a reduction in their rate of decline of 67% (p=0.001) in the Phase 2 follow-on trial, compared to the placebo patient rate of decline over the first 12 months.
5. Time to Psychiatric Events (TPE). This measure assesses the time to the first psychiatric event such as aggression, depression, confusion and agitation. Delaying the time before a patient experiences these types of events or reducing the number of events may keep patients out of nursing care facilities. Patients on 800 mg twice daily Flurzan had fewer events (p=0.020) and those events were delayed by more than 227 days (p=0.011) compared to patients on placebo after 12 months in the Phase 2 study.
6. Dose Response. Plasma concentrations of Flurizan were significantly correlated with the size of the benefit to patients, so that the more Flurizan patients had in their blood, the more they benefited in reduction of decline on measures of Alzheimer's disease.
"Flurizan has been a well tolerated drug in the elderly in studies to date that total over 1,200 patient-years of safety data," said Adrian Hobden, Ph.D., President of Myriad Pharmaceuticals, Inc. "We are very pleased with the speed of the enrollment in the global Phase 3 trial and we look forward to confirming our belief that Flurizan can provide significant benefit to patients with mild Alzheimer's disease."
SOURCE: Myriad Genetics, Inc.