Positive top-line data in patients with mild to moderate Alzheimer's

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Memory Pharmaceuticals Corp. (Nasdaq: MEMY) announced positive top-line data from the randomized, placebo-controlled, multi-center Phase 2a proof-of-concept trial of MEM 3454, the Company's lead nicotinic alpha-7 receptor partial agonist, in 80 patients with mild to moderate Alzheimer's disease over an eight week treatment period. The trial was an exploratory efficacy study to learn about MEM 3454 as a potential treatment for Alzheimer's disease. The primary endpoint of the trial was the change from baseline in the Quality of Episodic Secondary Memory (QESM) factor score of the Cognitive Drug Research (CDR) battery. QESM is a composite score derived from memory tests in the CDR battery that measure the ability to store, hold and retrieve information. There were three oral daily doses of MEM 3454 tested in the trial, 5 mg, 15 mg and 50 mg. The CDR battery was administered at baseline and on six days during the treatment period, at four time points (pre-dosing and 2, 4 and 8 hours post-dosing) each day. For the eight hour post-dose time points over the treatment period, subjects receiving 5 mg and 15 mg of MEM 3454 demonstrated a statistically significant effect on the QESM compared to placebo (p=0.023 and p=0.050, respectively).

Secondary endpoints in the trial included other composite scores from the CDR battery that measure working memory, attention and executive function, and the Alzheimer's Disease Assessment Scale -- cognitive subscale (ADAS-Cog). On secondary CDR battery measures, using all time points combined over the treatment period, the trial showed that the 5 mg and 15 mg doses achieved statistically significant positive results on Quality of Working Memory (p=0.031 and p=0.047). The 15 mg group also demonstrated trends to efficacy on Speed of Memory (p=0.080). Quality of Working Memory is a composite score derived from accuracy measures in the CDR battery that reflect how well subjects can hold information in working memory. The Speed of Memory composite score reflects the time it takes to recall an item from memory. For the ADAS-cog, the 15 mg group showed numeric improvements favoring treatment over placebo. There were two additional secondary endpoints in the study from the CDR battery, Power of Attention and Continuity of Attention, and on these measures the study found no statistically significant differences between treatment and placebo. The 50 mg group also showed no statistically significant differences favoring treatment at any endpoint in the study.

In analyses of QESM at certain other time points, and for all time points combined, the placebo group performed statistically significantly better than the treatment groups due to substantially lower QESM scores at baseline for the placebo group, at the 2 and 4-hour time points, as compared to the treatment groups. After adding a covariate for baseline scores to the statistical model, the MEM 3454 5 mg group demonstrated a statistically significant change from baseline on QESM at all time points combined compared to placebo (p=0.032). The MEM 3454 5 mg and 15 mg dose groups demonstrated statistical significance (p=0.003 and p=0.023, respectively), and the 50 mg dose group demonstrated a trend favoring treatment (p=0.083) for the eight hour post-dose time points on QESM. In addition, the 5 mg and 15 mg dose groups demonstrated a statistically significant effect on Quality of Working Memory, over all time points combined (p=0.006 and p=0.004, respectively). The 5 mg dose group also demonstrated a statistically significant effect on Speed of Memory (p<0.001) over all time points combined.

"Overall, the data from this study demonstrate that MEM 3454 is providing cognitive benefit and these results are consistent with our previous work with this compound in volunteers. When an appropriate baseline covariate is included, the results of this trial are even more robust," stated Keith Wesnes, Ph.D., the developer of the CDR battery. "It is exciting to improve the ability of Alzheimer's patients to store and retrieve information from both working and episodic memory, not only in terms of accuracy but also speed. These improvements have clinical relevance."

"We believe these trial results provide evidence of MEM 3454's potential to treat Alzheimer's disease," stated Stephen R. Murray, M.D., Ph.D., Chief Medical Officer of Memory Pharmaceuticals. "This data is consistent with our preclinical and Phase 1 results and reinforces our belief that MEM 3454 warrants continued development. We look forward to commencing our Phase 2a trial of MEM 3454 in cognitive impairment associated with schizophrenia in the near term."

MEM 3454 was well-tolerated in this trial, with the exception that the number of subjects with constipation was higher in the treatment groups (43%) compared to placebo (5%). There was one treatment-emergent serious adverse event in the 15 mg group, which was deemed not to be treatment-related by the investigator. http://www.sciencedaily.com

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