2005 - Predix Pharmaceuticals Announces Positive Findings from First Clinical Trial in Alzheimer's Disease Patients
11/14/2005 9:00:00 AM EST
PRX-03140 Preclinical Data to be Presented at the 35th Annual Meeting of the Society for Neuroscience
Predix Pharmaceuticals, a drug discovery and development company, announced today that PRX-03140, its highly selective, proprietary serotonin 4 (5-HT4) receptor agonist, showed the desired alterations in brain wave activity in patients with mild-to-moderate Alzheimer's disease and was well-tolerated in a recently completed 14-day Phase Ib clinical trial.
"The results of this Phase Ib trial in patients with Alzheimer's disease suggest that PRX-03140 is stimulating the 5-HT4 receptor in the brain and is eliciting the desired effects on brain waves consistent with approved drugs for Alzheimer's disease," said Stephen Donahue, M.D., vice president of clinical and regulatory affairs. "The excellent tolerability profile of PRX-03140 at all doses studied, combined with these early indicators of activity, are exciting preliminary results and warrant further evaluation in a Phase II trial."
Michael G. Kauffman, M.D., Ph.D., president and CEO of Predix, added, "We believe there is a significant unmet medical need for a well-tolerated, effective treatment for Alzheimer's disease that can be given once daily, and we are excited about the data we have seen from our experience with PRX-03140 in over 100 patients and healthy volunteers. We expect to initiate a Phase II dose-ranging trial in Alzheimer's disease patients early next year."
In parallel with these clinical development efforts, several positive studies of PRX-03140 in key preclinical models for memory, cognition, and disease modification are the subject of four poster presentations at the 35th Annual Meeting of the Society for Neuroscience in Washington, D.C. on November 12 - 16, 2005.
Study Design
This Phase Ib clinical trial was the second of two multiple dose studies with PRX-03140, Predix's proprietary drug candidate intended to treat Alzheimer's disease and other disorders of cognitive impairment. The primary objectives of these randomized, blinded Phase Ib studies in both healthy subjects and patients with mild-to-moderate Alzheimer's disease were to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of the compound over a 14-day period. A total of 110 healthy volunteers and 12 Alzheimer's patients were enrolled in the Phase I clinical trials.
The Phase Ib study in patients was a double-blind, placebo-controlled trial, in which patients with mild-to-moderate Alzheimer's disease received a once-daily dose of the study drug or placebo for 14 days. The trial assessed the effects of PRX-03140 on quantitative electroencephalograms (EEGs), a measure of the electrical activity in the brain that has been used to characterize the effects of drugs that act on the central nervous system. In Alzheimer's disease patients, a specific EEG slow wave pattern has been linked with severity of dementia. With PRX-03140 treatment of Alzheimer's disease patients, there was a statistically significant improvement in the quantitative EEG slow wave pattern when compared with placebo. The short-term EEG effects observed with PRX-03140 treatment are similar to the published effects seen in patients that have an improvement in cognitive function after months of treatment with approved acetylcholinesterase inhibitor therapies for Alzheimer's disease. As expected, no change was seen in clinical parameters in this two-week study.
In the single and multiple dose studies in healthy volunteers and Alzheimer's patients, adverse events have all been mild or moderate in intensity, with no serious adverse events or adverse events resulting in discontinuations. No significant gastrointestinal adverse events were observed. The drug concentrations in humans increased in proportion to increases in dose, with a half-life of 10-12 hours, indicating that the drug may be administered once daily.
About PRX-03140
PRX-03140 is Predix's second of three clinical drug candidates discovered utilizing computer-based GPCR models and optimized with integrated computational-medicinal chemistry. PRX-03140 is highly selective for the 5-HT4 receptor in the brain, and preclinical studies have shown that it improves cognitive function, as well as increases levels of acetylcholine (ACh), soluble amyloid precursor protein (sAPP) and brain-derived neurotrophic factor (BDNF) in regions of the brain known to be important for memory.
About Alzheimer's Disease
An estimated 4.5 million Americans have Alzheimer's disease (AD), with epidemiological data suggesting a growing increase in disease incidence with an aging population. Currently, nearly one in 10 people over age 65 and as many as five in 10 people over age 85 have AD. According to recent studies, by the year 2050, the range of individuals with AD could be from 11 million to 16 million.
Acetylcholinesterase (AChE) inhibitors, a class of drugs approved for the treatment of Alzheimer's disease, are active in patients provided that endogenous production of ACh is sufficient to maintain local levels. As Alzheimer's disease progresses, ACh production declines, and brain levels of this critical neurotransmitter decline. In parallel with effective therapeutics in other neurodegenerative diseases (e.g., Parkinson's Disease), replacement of the prominent neurotransmitter lost in Alzheimer's disease should provide significant clinical benefit. However, neither ACh nor its components can be given in sufficient quantities to increase brain ACh levels with tolerable side effects. The search for agents which increase the production and/or release of ACh, which can be used alone or in combination with AChE inhibitors, may therefore yield a drug candidate with significant clinical benefit. Early data suggest PRX-03140 may meet this need.
About Predix
Predix Pharmaceuticals Holdings, Inc. is a pharmaceutical company focused on the discovery and development of novel, highly selective, small-molecule drugs that target G-Protein Coupled Receptors (GPCRs) and ion channels. Using its proprietary drug discovery technology and approach, Predix has advanced three drug candidates into clinical trials and has six additional programs in preclinical development and discovery. Predix initiated the first of at least two pivotal Phase III clinical trials for generalized anxiety disorder for its lead drug candidate, PRX-00023, in August 2005. It has two other clinical-stage drug candidates: PRX-03140 for the treatment of Alzheimer's disease, entering Phase II, and PRX-08066 for the treatment of pulmonary arterial hypertension.
CONTACT:
Predix Pharmaceuticals Kim Drapkin, 781-372-3272 or Andrea Johnston, 910-681-1088
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