Start Of Phase 2b Right-heart Catheter Study Of PRX-08066 In Patients With Chronic Obstructive Pulmonary Disease And Moderate-To-Severe PH

Main Category: Respiratory / Asthma
Also Included In: Cardiovascular / Cardiology
Article Date: 13 Aug 2008 - 1:00 PDT

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EPIX Pharmaceuticals, Inc. (NASDAQ:EPIX), 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, M.D., 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 enroll 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 remodeling 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.

About PRX-08066

Discovered and designed using EPIX's proprietary G-protein coupled receptor (GPCR) modeling 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.

In a Phase 2a, randomized, double-blind, placebo-controlled trial of 71 patients, 62 of whom were evaluable, treatment with PRX-08066 resulted in statistically significant (p=0.043) reductions in median systolic pulmonary artery pressure (SPAP) compared with placebo after two weeks of treatment. Responder (defined as greater than or equal to a 4mmHg drop in SPAP) rates were 45% on 400 mg of PRX-08066 given once-daily vs. 14% on placebo. The company has also completed several Phase 1 trials with PRX-08066 in healthy volunteers, including a Phase 1b study that assessed the effects of PRX-08066 on pulmonary artery blood 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 vs. placebo), without affecting systemic blood pressure. The half life of PRX-08066 is approximately 20 hours and the agent has shown good oral absorption. PRX-08066 was well-tolerated when given alone and when combined with standard medications for COPD patients as all of the patients in the Phase 2a trial were on several concomitant medications. One patient in the 400 mg dose group who continued into the six-week open-label extension experienced a modest increase in liver enzyme levels at the end of the extension that was believed to be drug-related. These values returned to normal within two weeks and the patient remained asymptomatic.

About EPIX

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. The company has a pipeline of internally-discovered drug candidates currently in clinical development to treat diseases of the central nervous system and lung conditions. EPIX also has collaborations with leading organizations, including GlaxoSmithKline, Amgen, Cystic Fibrosis Foundation Therapeutics and Bayer Schering Pharma.

This news release contains express 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 our Phase 2b study of PRX-08066 in patients with COPD and moderate-to-severe PH and the potential efficacy of PRX-08066. 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 PRX-08066 may fail in the clinic or may not be successfully marketed or manufactured; risks relating to our ability to advance the development of PRX-08066; failure to obtain the financial resources to complete development of PRX-08066; our inability to achieve commercial success for our products and technologies; our failure to comply with regulations relating to our products and product candidates, including FDA requirements; the risk that the FDA may interpret the results of our studies differently than we have; 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 and subsequent Quarterly Reports on Form 10-Q.

EPIX Pharmaceuticals