Trial Of MEM 1003 In Alzheimer's Disease Shows Positive Results
Memory Pharmaceuticals announced top-line data from the multi-center, randomized, double-blind, placebo-controlled Phase 2a study of MEM 1003, a neuronal L-type calcium channel modulator, in Alzheimer's disease. The trial enrolled 183 subjects with mild to moderate Alzheimer's disease at over 40 centers in the United States and included monotherapy subjects and subjects on stable doses of cholinesterase inhibitors. The trial failed to meet its primary endpoint, which was a twelve-week mean change in the Alzheimer's disease Assessment Scale -- Cognitive subscale (ADAS-cog) score in the overall population.
The negative results were largely driven by an unusually large placebo response in the subgroup of monotherapy subjects. In the subgroup of subjects receiving cholinesterase inhibitors, the change in ADAS-cog favored treatment over placebo, although this difference was not statistically significant. Similarly, in this subgroup, numeric improvements were seen in all of the four secondary endpoints, which included the Mini-Mental State Exam, the Alzheimer's Disease Cooperative Study -- Activities of Daily Living, the Clinician Interview-Based Impression of Change with Caregiver Input and the Neuropsychiatric Inventory.
"Based on this information, I believe that further development of this compound merits consideration," said Pierre N. Tariot, M.D., Professor of Research Psychiatry, Director of the Memory Disorders Center of the Banner Alzheimer's Institute in Phoenix, and chairman of the study's data and safety monitoring board.
"While we are disappointed that the trial did not meet the primary endpoint, we are encouraged by the favorable trend seen in the subgroup of subjects receiving cholinesterase inhibitors," said Stephen R. Murray, M.D., Ph.D., Chief Medical Officer. "Clearly there is a significant need for new options for the treatment of Alzheimer's disease, and we believe that the effects of MEM 1003 seen in this study warrant further investigation."
Subjects participating in the study were randomized at enrollment into one of three treatment groups -- 30 mg of MEM 1003 twice a day, 90 mg of MEM 1003 twice a day or placebo twice a day. During the double-blind treatment segment of the study, subjects received MEM 1003 or placebo for a period of 12 weeks, which was followed by a four-week single-blind placebo treatment. Secondary measures assessed changes in activities of daily living, behavior and global function.
MEM 1003 was generally well-tolerated in the trial. The rates of treatment-emergent adverse events were similar in all arms of the trial. There were seven treatment-emergent serious adverse events (SAEs) in five subjects, including two deaths. Four of the subjects were in the 30 mg dose group and the fifth subject was in the 90 mg dose group. None of the SAEs were deemed to be treatment-related by the investigators.
The Company expects to report top-line results from its Phase 2a clinical trial of MEM 3454, its lead nicotinic alpha-7 agonist, in Alzheimer's disease by the middle of the fourth quarter.
MEM 1003 is a neuronal L-type calcium channel modulator that Memory Pharmaceuticals is developing for the treatment of Alzheimer's disease. By blocking L-type calcium channels, MEM 1003 may regulate the flow of calcium and reestablish normal levels of calcium, which may help treat and prevent the onset of Alzheimer's disease.