EPIX Pharmaceuticals, Inc a biopharmaceutical company focused on discovering and developing novel therapeutics through the use of its proprietary and highly efficient in silico drug discovery platform, announced that it has initiated its phase-2b right-heart catheter study of PRX-08066 in patients with chronic obstructive pulmonary disease (COPD) and moderate-to-severe pulmonary hypertension (PH). PRX-08066 is a novel serotonin type 2B receptor (5-HT2B) antagonist that may represent a new mechanism of action for treating PH.

"There are currently no approved drugs to treat PH associated with COPD and it is estimated that this disease may affect up to six million people worldwide," said Elkan Gamzu, Ph D, interim chief executive officer of EPIX. "These patients have a very poor prognosis and, consequently, there is a significant unmet medical need for an effective treatment. We believe that PRX-08066 may be the only 5-HT2B antagonist being developed for pulmonary hypertension that has the potential to selectively and safely reduce pulmonary artery blood pressure in these patients without affecting their systemic blood pressure."

"There is an undeniable need for safe and effective treatments for patients with PH associated with COPD," said Aaron Waxman, MD, Ph D, assistant professor of medicine, Harvard Medical School and Massachusetts General Hospital, Pulmonary and Critical Care Medicine and lead investigator of this Phase 2b study. "We believe this drug may be an important advance toward effective treatment for patients with this progressive lung disease, and hope to see reductions in pulmonary artery blood pressure and improvements in exercise capacity in this trial similar to those seen in previous trials with PRX-08066 using more rigorous techniques."

This single-arm, open-label, phase-2b study is designed to evaluate the mean pulmonary artery blood pressure change from baseline as measured directly by right-heart catheterization and will also measure the change from baseline in the standard six-minute walk distance test after three months of treatment. Patients will be treated with 500 mg of PRX-08066 on day one of the trial followed by twice-daily dosing of 300 mg of PRX-08066 for three months. The trial is designed to enrol adult patients with COPD and moderate-to-severe PH.

PRX-08066 may represent a novel mechanism for selectively dilating diseased pulmonary arteries without affecting systemic blood pressure. Expression of the 5-HT2B receptor is increased in the pulmonary arteries of patients with PH. Blocking the 5-HT2B receptor in patients with PH may reduce or prevent the acute rise in pulmonary blood pressures which occurs when patients increase their activity. This mechanism means that the heart would do less work for a given level of activity, allowing for improvements in exercise tolerance. Moreover, by blocking the serotonin-dependent growth of pulmonary vascular smooth muscle cells, which further increases pulmonary blood pressures and increases workload demand on the heart, PRX-08066 could potentially slow the progression of PH. Over time, this effect could translate into long-term improvements in exercise tolerance and slowing of the vascular and cardiac remodelling that leads to right heart failure. These kinds of effects have been seen with PRX-08066 in pre-clinical animal models of hypoxia-induced pulmonary hypertension.

COPD is a progressive lung disease that affects nearly 30 million people worldwide and is characterized by airflow obstruction which interferes with normal breathing and impairs the ability to exercise and perform daily activities. According to a December 2005 Datamonitor report, PH is estimated to be present in up to 20 percent of patients with COPD. Despite the fact that patients with COPD and concomitant moderate-to-severe PH generally have poor prognoses, there are no agents currently approved to treat this patient population.

Discovered and designed using EPIX's proprietary G-protein coupled receptor (GPCR) modelling and optimization technology, EPIX is developing PRX-08066 to provide both symptomatic improvement of PH, through selective dilation of diseased pulmonary arteries, and to also slow disease progression by inhibiting the serotonin-mediated thickening of the pulmonary artery vessels. EPIX believes PRX-08066 may be a first-in-class selective antagonist of the 5-HT2B receptor for the treatment of PH.

EPIX Pharmaceuticals is a biopharmaceutical company focused on discovering and developing novel therapeutics through the use of its proprietary and highly efficient in silico drug discovery platform.