Myriad Genetics Inc. said preliminary Phase II data pointed to positive trends among certain Alzheimer's disease patients on Flurizan, its lead product candidate, though the study did not achieve statistical significance.
Nevertheless, the Salt Lake City company plans to continue a Phase III trial with some modifications based on the Phase II findings. Those data showed encouraging tendencies on all three primary endpoints in mild Alzheimer's patients who received 800-mg, twice-daily doses of Flurizan. Also, those mild patients who achieved high plasma concentrations of the drug demonstrated a statistically significant effect in two of the three primary endpoints.
Such findings weren't a complete surprise, the company said, given the drug's mechanism of action as a selective amyloid beta 42 lowering agent and the hypothesis that points to amyloid deposits as the cause of the disease.
"We thought that patients earlier in their disease should be affected first," Adrian Hobden, the president of Myriad's pharmaceutical division, said during a conference call, "and more severe patients might take longer to show an effect."
The double-blinded, placebo-controlled Phase II study included mild and moderate patients, though the latter group did not respond as well to treatment. Among possible changes to the Phase III protocol would be to focus future enrollment on mild patients, subject to regulatory approval.
"This Phase II data will be very useful," Myriad President and CEO Peter Meldrum said, "as we look at modifying the current Phase III protocol to improve the study's design and focus."
Enrollment in the 750-patient study began early this year to test primary efficacy endpoints such as changes in cognitive function, as assessed by the Alzheimer's Disease Assessment Scale-cognitive subscale test (ADAS-cog), and changes in daily living activities. It has been testing twice-daily doses of 400 mg and 800 mg, though based on the latest data the company now believes the latter to be the preferred dose of Flurizan. (See BioWorld Today, Jan. 13, 2005.)
The year-long, 207-patient Phase II study also included twice-daily doses of 400 mg of the drug, which was well tolerated throughout the trial. Myriad plans to further analyze its findings to better understand Flurizan's effect on moderate patients.
The primary endpoints measured a trio of disease assessment scales: the ADAS-cog, the Alzheimer's Disease Cooperative Study - Activities of Daily Living inventory (ADCS-ADL) and the Clinical Dementia Rating - Sum of Boxes (CDR-sb).
Mild patients who received the dose demonstrated a 44 percent slowing of decline in their performance of daily activity, as measured by the ADCS-ADL scale. The same group demonstrated a 41 percent slowing of decline during the study in global function as measured by the CDR-sb evaluation and a 29 percent slowing of cognitive decline, as measured by the ADAS-cog scale.
"Slowing the rate of decline of Alzheimer's disease by this magnitude," Hobden said, "suggested that these results might mean that we keep patients out of nursing homes for three or more years longer than if they had no treatment."
A further analysis of data from 128 mild patients indicated that those who achieved the greatest plasma concentrations of Flurizan demonstrated a statistically significant 67 percent reduction in decline in activities of daily living (p=0.017, two-sided) as measured by ADCS-ADL, compared to placebo patients. That finding was confirmed by analyzing the same group of patients vs. the control group for the global function assessment, which showed a 54 percent slower decline (p=0.034, two-sided) as measured by CDR-sb. Also, the high plasma concentration group demonstrated a non-statistically significant 30 percent slowing in the rate of decline of cognitive function as measured by ADAS-cog.
"It appears from this study that Flurizan, even when taken in addition to standard-of-care drugs - the cholinesterase inhibitors - has the potential to slow the rate of decline of Alzheimer's disease in mild patients," Hobden said. But he also conceded that placebo patients declined at a slower rate than historical controls. The company plans to report full results next month at a scientific meeting in Washington.
Beyond Alzheimer's, Flurizan also has been tested for use in prostate cancer patients and remains in Phase IIb for that indication. Myriad owns all rights to the drug.
On Monday, its shares (NASDAQ:MYGN) fell 1 cent to close at $16.15.