West Coast Editor
Cardiome Pharma Corp.'s oxypurinol fizzled in top-line results from a Phase II trial against congestive heart failure, missing the primary and secondary endpoints, but officials will sift the data further before making a decision on the fate of the program.
The company's stock (NASDAQ:CRME) closed Monday at $6.27, down 61 cents.
"Expectations were low for the program," Doug Janzen, chief financial officer of Vancouver, British Columbia-based Cardiome, told BioWorld Today, calling the oxypurinol "almost like a warrant on the stock. If [the drug] had worked, it would have been great."
The patient population targeted in the trial was challenging, "but we knew it was the right test," he added.
Oxypurinol, acquired through the 2002 buyout of New York-based Paralex Inc., is an oral xanthine oxidase inhibitor that was given to 405 CHF subjects at 600 mg daily for 24 weeks. The study measured outcomes in New York Heart Association Class 3 and Class 4 patients.
Failing to show a statistically significant benefit over placebo in the primary composite endpoint (p=0.357), oxypurinol also yielded no benefits over placebo in the Minnesota CHF Quality of Life index or time to acute clinical events, such as mortality or re-hospitalization for heart failure.
"We were trying to show that patients on standard therapy would have their heart failure well controlled" when oxypurinol was added, Janzen said.
The primary endpoint composite was made up of factors that included the NYHA class, the patient's global heart failure status, and any hospitalization, emergency room, or emergency office/clinic visit for worsening heart failure. Also part of the endpoint mix were administration of a new drug class for heart failure or intravenous diuretics for worsening disease, permanent withdrawal of study drug due to worsening condition, and cardiovascular death.
Randomized and double-blinded, the 53-center trial began in March 2003 and enrolled patients with ejection fractions less than or equal to 40 percent, with study visits made every four weeks.
In April, Cardiome released data from a clinical study with 400-mg oxypurinol in 20 CHF patients, which showed a statistically significant improvement in left ventricle ejection fraction, but that trial was open-label with no placebo group.
"It's one of our driving goals here to put [drugs] in the right Phase II programs and kill them or prove they have utility early on in the development," Janzen said. With oxypurinol, further analysis is yet to be done but "my gut feeling is that, as we go through the data deeper, our first conclusions will bear out to be the right ones," he said.
The oxypurinol program is one of three under way at Cardiome, which has two drugs targeting atrial arrhythmia. Farthest along is the I.V. version of RSD1235, which the company also is developing as an oral drug to maintain normal heart rhythm. Top-line results from ACT 1, the first of three Phase III trials for I.V. formulation, were disclosed in December 2004 and February. (See BioWorld Today, Dec. 21, 2004.)
Cardiome expects to file a new drug application "late this year or early next year," Janzen said. "We also want to in-license more programs and continue to build the franchise."
The anti-arrhythmia program is "where 90 percent of the value" of the company has been, he said.