The data also suggest that during the follow-on period from months 12 to 24, the benefit of Flurizan increases in terms of both effect size and significance, the longer patients remain on Flurizan. At month 24, patients taking 800 mg of Flurizan BID had an effect size of 72%, with a highly significant value of p=0.0005, as measured by their global function on the CDR-sb test. In terms of the performance of activities of daily living (ADCS-ADL) at 24 months, the patients showed a 67% effect size, with a value of p=0.015, which is also significant. Flurizan is improving the rate of cognitive decline also, as shown by the effect size of 52% at 24 months on the ADAS-cog scale. These data suggest that there was a substantial benefit from Flurizan on activities of daily living and global function, and that the benefit was increasing over time.
The vast majority (~94%) of patients in this Phase 2 study, at the time of enrollment, were receiving stable doses of acetylcholinesterase inhibitors, FDA-approved drugs for symptomatic treatment of Alzheimer's disease, at the time of enrollment. Thus, the benefits of Flurizan observed in these patients were over and above the current standard of care.
"The 24 month data completes the Phase 2 follow-on trial with mounting evidence of efficacy against mild Alzheimer's disease that consistently increased over the course of the study," said Adrian Hobden, Ph.D., President of Myriad Pharmaceuticals, Inc. "The results are consistent with a mode of action for Flurizan that is modifying the course of the underlying disease process."
Importantly, the Phase 2 trial also studied the occurrence and timing of serious psychiatric events in patients with Alzheimer's disease. The occurrence of psychiatric problems such as agitation, aggression, confusional state and depression was monitored throughout the study. Over the course of the 12-month study, approximately 35% of participants taking placebo experienced such an event. However, patients on 800 mg BID Flurizan experienced a 60% reduction in psychiatric events (14%, p=0.020) compared to those on placebo and the time to such an event was significantly longer with patients on Flurizan than those on placebo (333 days vs. 106 days, a difference of over 7 months, p=0.011). These data provide an indication that their disease had progressed more slowly than those on placebo.
"The decrease in the number of psychiatric events and the dramatic lengthening in time before patients experienced such events while on Flurizan is an important feature for spouses and caregivers of Alzheimer's patients, as well as for the patients themselves," said Jacobo Mintzer, M.D., Professor in the Departments of Psychiatry and Neurosciences and Director of the Alzheimer's Disease Program at the Medical University of South Carolina, who is presenting the psychiatric event findings at the conference. "These events can be as troubling as the more widely recognized memory loss and decline in cognition to those involved in the devastating deterioration caused by Alzheimer's disease."
After completion of Myriad's 12-month Phase 2 trial of Flurizan, study participants who had previously received placebo during the Phase 2 trial were randomized into the 400 mg BID group or the 800 mg BID group. In this "randomized start" design, former placebo patients were then followed for an additional 12 months. Results from this analysis indicate that patients treated with 800 mg twice daily of Flurizan for 24 months decline more slowly with regard to cognition, activities of daily living, and global function than those treated with the same dose for just 12 months in the follow-on study. Additionally, those former placebo patients who were randomized onto 800 mg Flurizan twice daily declined more slowly than those randomized onto 400 mg on both the ADAS-cog and the CDR-sb measures of disease progression. On the ADCS-ADL measure, the two groups experienced a comparable decline. Unlike currently marketed drugs for Alzheimer's disease, which show only symptomatic benefit, there was no indication that patients who had been on placebo for 12 months would catch up to patients treated for all 24 months. We believe these results are consistent with the hypothesis that Flurizan may have disease modifying properties and that the longer patients with mild Alzheimer's disease are treated with Flurizan, the slower their disease will progress.
Myriad has begun to enroll a Global Phase 3 trial in patients with mild Alzheimer's disease including investigators in Italy, France, Germany, Spain, Sweden, Switzerland, the United Kingdom, Netherlands, the United States, Belgium, Canada and Denmark. The trial will enroll approximately 800 participants into two groups, 800 mg twice daily and placebo, and the participants will receive treatment for 18-months.
"We are encouraged by the promising data from our Phase 2 study of Flurizan in patients with Alzheimer's disease," said Peter Meldrum, President and Chief Executive Officer of Myriad Genetics, Inc. "Based on that data, we have advanced our development plans and are pleased to announce that Myriad has enrolled its first patients in a new global Phase 3 trial."
Myriad is also enrolling patients with mild Alzheimer's disease into a Phase 3 trial, at 130 centers across the United States. This enrollment is well advanced and is expected to be complete this summer. The Phase 3 trial is a double blind, placebo-controlled trial. Patients will be randomized into one of two groups, receiving either 800 mg of Flurizan or placebo twice daily for the duration of the 18-month trial period. The study is designed to determine Flurizan's ability to reduce the rate of cognitive decline and activities of daily living in patients with mild Alzheimer's disease, as measured by ADAS-cog and ADCS-ADL, respectively. Information on participation is available by calling (888) 459-4888.
Flurizan is the first in a new class of drug candidates known as Selective Amyloid beta-42 Lowering Agents (SALAs). Flurizan lowered levels of Abeta42 in cellular assays and animal models. Abeta42 is the primary constituent of senile plaque that accumulates in the brain of patients with Alzheimer's disease. It is thought to be the key initiator of Alzheimer's disease, since Abeta42 has the greatest tendency to aggregate, cause neuronal damage and initiate amyloid deposits in the brain. Most genetic mutations that cause early-onset Alzheimer's disease appear to do so by increasing production of Abeta42. Myriad believes that Flurizan is the most advanced drug candidate that modifies the production of Abeta42 to be evaluated in a clinical trial for the treatment of Alzheimer's disease.
Myriad Genetics, Inc. is a biopharmaceutical company focused on the development and marketing of novel healthcare products. The Company develops and markets molecular diagnostic products, and is developing and intends to market therapeutic products. Myriad's news and other information are available on the Company's Web site at www.myriad.com.
Flurizan is a trademark of Myriad Genetics, Inc. in the United States and other countries.
This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These forward looking statements include: the suggestion that study participants taking 800 mg BID of Flurizan demonstrated a substantial benefit over other dose groups in the study and that his benefit continued to increase over 24 months; the suggestion that continued treatment with Flurizan will provide continued and increasing benefits in both effect size and significance in patients with mild Alzheimer's disease the longer patients remain on Flurizan; that Flurizan offers benefits over and above the current standard of care; the decrease in psychiatric effects and the indication that Alzheimer's disease progresses more slowly for patients on Flurizan; the belief that Flurizan may have disease modifying properties and that the longer patients with mild Alzheimer's disease are treated, the slower their disease will progress; the appearance that Flurizan is modifying the underlying course of the disease process; the continued encouragement of the Company by the potential of Flurizan to treat mild Alzheimer's disease; the anticipated completion of enrollment in the Phase 3 trial in order to confirm similar efficacy results for Flurizan in a larger population; the enrollment of patients with mild Alzheimer's disease in a global Phase 3 trial; the continued, on schedule, enrollment of patients with mild Alzheimer's disease in the Company's Phase 3 trial at 130 U.S. sites; the design of the Phase 3 study, and the ability of the Phase 3 study, to successfully determine Flurizan's ability to alter the course of cognitive decline and functional change in patients with mild Alzheimer's disease as measured by the ADAS-cog test, and the change in ADCS-ADL, respectively; and the belief that Flurizan is the most advanced drug candidate in a clinical trial that inhibits the production of Abeta42 to be evaluated in a clinical trial for the treatment of Alzheimer's disease. These forward looking statements are based on management's current expectation and are subject to certain risks and uncertainties that could cause actual results to differ materially from those set forth or implied by forward-looking statements. These include, but are not limited to, uncertainties as to the extent of future government regulation of Myriad Genetics' business; uncertainties as to whether Myriad Genetics and its collaborators will be successful in developing, and obtaining regulatory approval for, and commercial acceptance of, therapeutic compounds; the risk that markets will not exist for therapeutic compounds that Myriad Genetics develops or if such markets exist, that Myriad Genetics will not be able to sell compounds, which it develops, at acceptable prices; and the risk that the Company will not be able to sustain revenue growth for its predictive medicine business and products. These and other risks are identified in the Company's filings with the Securities and Exchange Commission, including the Company's current Report on Form 8-K filed October 28, 2005. All information in this press release is as of July 19, 2006 and Myriad undertakes no duty to update this information unless required by law.