Myogen Inc. started enrolling two pivotal Phase III trials for ambrisentan, a Type A selective endothelin receptor antagonist for the treatment of pulmonary arterial hypertension.
Initiation of the Phase III program means Myogen, a Denver-based company, has three late-stage development candidates, when adding to its lead product, enoximone, a small organic molecule being studied in heart failure; and darusentan, an ETA selective endothelin receptor antagonist in trials for uncontrolled hypertension.
The ambrisentan program aims to enroll 186 patients in each of two trials designed to evaluate exercise capacity measured by the six-minute walk test, Derek Cole, Myogen's director of investor relations, told BioWorld Today.
Since the trials are just getting under way, Cole said it's too early to discuss a timeline for completion or regulatory filing.
In a prepared statement, William Freytag, Myogen's president and CEO, said: "The rapidity with which [the trials] began enrolling patients is encouraging given some of the challenges we face regarding competing trials and the availability of existing medications. We hope that we can maintain this early momentum throughout the remainder of the studies."
Competing medications include Remodulin (treprostinil sodium) from United Therapeutics Corp., of Silver Spring, Md., and Tracleer (bosentan) from Actelion Inc., of Allschwil, Switzerland.
Ambrisentan, a small peptide hormone, works by preventing the constriction of blood vessels and increasing blood flow to vital organs. The company said it believes ambrisentan will capture a share of the pulmonary arterial hypertension market due to a long half-life, possibly allowing it to be dosed once a day. In Phase II studies, data indicated a low incidence of abnormal liver function, and there were no significant drug-to-drug interactions.
The Phase III trials, referred to as ARIES I and II, are randomized, double-blind and placebo-controlled. They are identical except for the doses of ambrisentan and the geographical locations of the investigative sites. ARIES I will evaluate ambrisentan doses of 5 mg and 10 mg, administered orally once daily for 12 weeks to patients in the U.S. and Canada. ARIES II will evaluate ambrisentan doses of 2.5 mg and 5 mg, administered once daily for 13 weeks to patients in Europe and South America.
Myogen acquired exclusive worldwide rights to ambrisentan from Abbott Laboratories, of Abbott Park, Ill., in late 2001 for an undisclosed up-front fee, milestones and royalties. (See BioWorld Today, Nov. 30, 2001.)
Cole said the company might consider partnering the candidate at some point. "We will look at all possibilities for maximizing what we can do with all of our compounds. We are open to partnering discussions, but we'll really look to pursue the most economically beneficial strategy," he said.
Two months after raising $40 million in a Series D financing, Myogen in late October completed its initial public offering, netting $73.2 million. (See BioWorld Today, Aug. 29, 2003, and Oct. 31, 2003.)
While year-end and fourth-quarter financials have not been released, Cole said he expects that the company ended 2003 with between $113 million and $117 million in cash.
Myogen's stock (NASDAQ:MYOG) closed Thursday at $16.42, up 19 cents.