Target Indication: Alzheimer's disease
Millions of families live each day with acute awareness of the ravages of Alzheimer's disease-a progressive, degenerative disorder that destroys the brain's nerve cells and, along with them, memory, cognition, language skills, and basic body functions.
Compounding the challenge these families face in caring for loved ones while watching their personality and life skills worsen is the sobering fact that there is no cure for Alzheimer's, or a way to slow its progressive nature.
At EPIX, we are working diligently each day to change that. We believe that our drug candidate PRX-03140 has the potential to improve cognition and memory, and to slow the progression of Alzheimer's disease, with fewer and less-severe side effects than drugs currently on the market to treat this condition.
PRX-03140 is a novel, highly selective, small-molecule agonist of a specific GPCR known as 5-HT4 for the treatment of Alzheimer's disease. In December 2007 and January 2008, EPIX announced the compelling results of a Phase 2a clinical trial of PRX-03140 as a single agent and in combination with Aricept® in patients with mild Alzheimer's disease.
These Phase 2a results indicated that patients receiving daily oral 150 mg doses of PRX-03140 as monotherapy achieved a mean 3.6 point improvement on the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) versus a 0.9 point worsening in patients on placebo (p= 0.021). The ADAS-cog endpoint is the current standard for evaluating drug efficacy for cognition in Alzheimer's disease and is an established and accepted registration endpoint. PRX-03140 was well tolerated as monotherapy and in combination with donepezil (Aricept®) with no serious drug-related adverse events.
In three Phase 1 trials and this Phase 2a trial, with more than 180 patients and healthy subjects, PRX-03140 has been well tolerated. In a 14-day Phase 1b clinical trial, treatment with PRX-03140 resulted in changes in brain wave activity in Alzheimer's patients that are consistent with those seen in clinical trials with currently approved drugs for Alzheimer's disease. In preclinical studies, PRX-03140 has shown to improve cognitive function through increasing levels of acetylcholine, soluble amyloid precursor protein (sAPP) and brain-derived neurotrophic factor (BDNF) in regions of the brain known to be important for memory.
PRX-03140 is one of EPIX's four drug candidates currently in clinical trials discovered utilizing its proprietary computer-based G-Protein Coupled Receptors (GPCR) platform and optimized with integrated computational-medicinal chemistry. In May 2008, EPIX announced the initiation of its Phase 2b program in Alzheimer's disease. The Phase 2b proof-of-concept program consists of two clinical trials - a six-month trial evaluating PRX-03140 in combination with donepezil and a three-month trial studying PRX-03140 as monotherapy. The combination trial began in May 2008 and the monotherapy trial was initiated in June 2008. For information about these two ongoing clinical trials, please visit ClinicalTrials.gov and use the search terms EPIX and/or PRX-03140.
5-HT4 Agonist - Potential Mechanism of Action
