The randomized, double-blind, placebo-controlled Phase 1b, multiple ascending dose clinical trial was designed to study the safety, tolerability, pharmacokinetics, and pharmacodynamics of PRX-07034 administered orally once-daily for 28 days in a population of obese, but otherwise healthy, adults (average weight 100kg or 220 pounds). The 33-person trial, which was conducted in an in-patient setting, included measures to assess potential effects on cognitive function and obesity. Highlights from the study include: -0-
-- Primary endpoint: safety and tolerability. -- PRX-07034 was well tolerated up to 600 mg once per day. No dose limiting toxicity was identified, and no serious adverse events were reported. There were no withdrawals due to adverse events. -- PRX-07034 demonstrated predictable pharmacokinetics with dose proportional increases in exposures, and a half-life supporting once-daily administration. -- Secondary endpoint: cognitive function (CogScreen(TM) test battery). -- Overall results on cognitive function showed a dose-dependent trend for improvement associated with PRX-07034. -- For the predetermined endpoint that combines speed and accuracy, there was a dose-dependent effect which was statistically significant (p=0.014 vs. placebo) at the 600 mg dose. -- Additional findings: signals suggestive of pharmacologic activity were observed for obesity, even in the in-patient setting. -- A greater proportion of subjects on drug experienced weight loss during the o ne month period than subjects on placebo.
"We are very pleased with the tolerability and pro-cognitive effects observed in this Phase 1b clinical trial of PRX-07034," said Michael G. Kauffman, M.D., Ph.D., chief executive officer, EPIX Pharmaceuticals. "These data support plans to initiate further clinical trials to evaluate the efficacy of PRX-07034 in obesity, cognitive impairment associated conditions, or both. We will continue to evaluate the data and provide an update on our plans in the coming months."
Dr. Kauffman added, "We are continuing to advance our pipeline of proprietary drug candidates and look forward to our next milestone - obtaining the results from our ongoing Phase 2a trial of PRX-08066 in pulmonary hypertension associated with chronic obstructive pulmonary disease, which we expect mid-year."
These results were announced this morning in an oral presentation by Kimberley S. Gannon, Ph.D., senior director of biology for EPIX, at the "ALZHEIMER'S DISEASE: From Molecular Mechanisms to Drug Discovery" conference in Punta Cana, Dominican Republic.
PRX-07034 is a novel, highly selective, small-molecule antagonist of a specific G-protein coupled receptor (GPCR) known as 5-HT6, which was discovered by EPIX using its proprietary in silico drug discovery platform. PRX-07034 has shown cognitive-enhancing properties in preclinical animal models of memory impairment, as well as reductions of both food intake and body weight in several preclinical animal models of obesity. The human 5-HT6 receptor is found predominantly in the central nervous system with little or no expression in peripheral tissues, which may result in fewer peripheral side effects.
CogScreen(TM) is a widely used tool that encompasses a battery of tests originally designed to assess memory and cognition in normal individuals with demonstrated utility in clinical trials of cognitive enhancers. CogScreen(TM) measures multiple cognitive domains including immediate memory recall; delayed memory recall; visual attention and memory; psychomotor/reaction time; and information processing.
EPIX Pharmaceuticals is a biopharmaceutical company focused on discovering, developing and commercializing novel pharmaceutical products through the use of proprietary technology to better diagnose, treat and manage patients. The company has five internally-discovered therapeutic and imaging drug candidates currently in clinical trials targeting conditions such as depression, Alzheimer's disease, cardiovascular disease and obesity. These drug candidates include PRX-08066 in Phase 2 clinical development for pulmonary hypertension associated with chronic obstructive pulmonary disease, PRX-03140 which is in a Phase 2a clinical trial in Alzheimer's disease, PRX-00023 which is in Phase 2b clinical development to treat major depression, and PRX-07034, which recently completed a Phase 1b trial and is in clinical development for the treatment of obesity and cognitive impairment. The company also has a blood-pool imaging agent (Vasovist(TM)) approved in 32 countries and marketed in Europe. EPIX has collaborations with leading organizations, including GlaxoSmithKline, Amgen, Cystic Fibrosis Foundation Therapeutics, and Bayer Schering Pharma AG, Germany.
This news release contains expressed or implied forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, that are based on current expectations of management. These statements relate to, among other things, our expectations regarding the progress and results of our clinical development program for PRX-07034, as well as PRX-08066 and other drug candidates. These statements are neither promises nor guarantees, but are subject to a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in these forward-looking statements. In particular, the risks and uncertainties include, among other things: risks that product candidates, including PRX-07034, may fail in the clinic or may not be successfully marketed or manufactured; risks relating to the our ability to advance the development of product candidates currently in the pipeline or in clinical trials, any failure to comply with regulations relating to our products and product candidates, including FDA requirements; failure to obtain the financial resources to complete development of product candidates; the risk that the FDA may interpret the results of our studies differently than we have; competing products may be more successful; our inability to interest potential partners in our technologies and products; our inability to achieve commercial success for our products and technologies; the possibility of delays in the research and development necessary to select drug development candidates; the risk that we may be unable to successfully secure regulatory approval of and market our drug candidates; and risks of new, changing and competitive technologies and regulations in the U.S. and internationally. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. We undertake no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise. For additional information regarding these and other risks that we face, see the disclosure contained in our filings with the Securities and Exchange Commission, including our most recent Annual Report on Form 10-K.
Kim C. Drapkin, 781-761-7602
Chief Financial Officer
Andrea L. Johnston, 910-616-5858