Target Indication: Pulmonary Hypertension Associated with Chronic Obstructive Pulmonary Disease
High blood pressure in the arteries that supply the lungs is called pulmonary hypertension. There are several types of pulmonary hypertension (PH). Pulmonary arterial hypertension (PAH) is a serious, often fatal cardiovascular disease characterized by elevation of pulmonary artery blood pressure and progressive thickening and narrowing of the blood vessels of the lungs, which can lead to heart failure. According to Datamonitor, the global market for PAH drugs is growing rapidly, from over $800 million in 2005, to an estimated $1.8 billion in 2010, as more patients with PAH are diagnosed and initiated on drug therapy.
COPD is a progressive lung disease characterized by airflow obstruction that 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 approximately 20 percent of patients who have COPD. These patients are generally known to have a very poor prognosis and currently there are no agents approved for this indication.
EPIX is currently developing what it believes to be the only selective 5-HT2B antagonist for pulmonary hypertension. In 2006, we completed two Phase 1 clinical trials with PRX-08066 in healthy volunteers, as well as a Phase 1b trial to assess the effects of PRX-08066. The Phase 1b trial assessed the effects of PRX-08066 on pulmonary artery pressure in athletes whose pulmonary pressures were increased by exposure to a reduced oxygen level (hypoxia). The results of this Phase 1b trial indicated that 200 mg of PRX-08066 given orally twice daily significantly reduced the increase in pulmonary artery blood pressure during hypoxic exercise (by 3.6mmHg compared with placebo), without affecting systemic blood pressure.
In August 2007, we announced positive, top-line results from our randomized, double-blind, placebo-controlled Phase 2a clinical trial of PRX-08066 in 71 patients with pulmonary hypertension (PH) associated with chronic obstructive pulmonary disease (COPD). Patients were randomized to one of three arms: 200 mg of PRX-08066 once-daily; 400 mg of PRX-08066 once-daily; or placebo. The two-week double-blind phase of the study was followed by an open-label extension in which 10 patients received 200 mg daily for six weeks.
The primary endpoints of the trial were safety and tolerability of PRX-08066. Efficacy was measured by the effect of PRX-08066 compared to placebo on systolic pulmonary artery pressure (SPAP) and included 58 evaluable patients who completed the double-blind portion of the study. The results show a statistically significant (p=0.017) dose-response for the patients that demonstrated a decrease of 4mmHg or more in post-exercise SPAP (responders). In the 400 mg dose group, 44% of the patients had a reduction in post exercise SPAP of 4mmHg or more versus 10% on placebo (p=0.026). An analysis of SPAP changes in all subjects revealed a dose response with median reductions of 1.1mmHg and 3.37mmHg in the 200 mg and 400 mg dose groups, respectively, compared with a 0.2mmHg increase on placebo (p=0.06 for high dose versus placebo). As observed in prior trials, PRX-08066 had no effect on systemic blood pressure, further demonstrating its selective pulmonary vasodilatory action.
In August 2008, EPIX announced the initiation of a Phase 2b right-heart catheter study of PRX-08066 in patients with chronic obstructive pulmonary disease (COPD) and moderate-to-severe pulmonary hypertension (PH).
Sources for the above are the EPIX site, the National Heart, Lung, and Blood Institute and the Pulmonary Hypertension Association.
