West Coast Editor
The Medicines Co. voluntarily suspended enrollment in its Phase III safety trials with the blood pressure drug Clevelox after about half the study's drug population showed what the company called a "puzzling" and "very surprising" rate of atrial fibrillation.
Wall Street didn't take the news too poorly, clipping the Parsippany, N.J.-based company's shares (NASDAQ:MDCO) by 7.9 percent, or $1.90, to end Monday at $22.27.
"I think the buy side and even the sell side agrees that Angiomax [the company's marketed anticoagulant] is essential to our story," said Michael Mitchell, Medicines Co.'s director of corporate affairs, who called Clevelox (clevipidine) "a good drug" but said the trial holdup is "not the end of the world."
Clevelox is designed to reduce blood pressure in cardiac surgery.
Atrial fibrillation, or irregular heartbeat, generally occurs on the second or third post-operative day following cardiac surgery in about one-third of patients. The incidence among patients randomized to Clevelox in the Phase III trials was well within the ranges reported in the cardiac surgery literature - but lower rates of the condition in the comparator groups led the firm to suspend the trial.
"There are still data from patients who have been enrolled, and those data are being cleaned," Mitchell said. "That's step No. 1. Then we will figure out what type of study we need to do to figure out this phenomenon."
He told BioWorld Today it's unclear whether a full new study would be required.
"We could probably do something smaller that would indicate whether there's a problem, and we could start back up, but we don't know" for certain, he said. Atrial fibrillation measures, Mitchell noted, are not part of the existing study's primary endpoint.
How long the analysis will take is not known, either. The company said earlier that it expected to file a new drug application for Clevelox in the fourth quarter.
"Obviously, we're off that timeline," Mitchell said.
Five trials make up the Clevelox Phase III program. The two efficacy studies, known as ESCAPE, finished last year and met their pre-specified trial objectives. The safety trials, know as ECLIPSE, are evaluating Clevelox perioperatively (immediately before, during and after surgery) in about 1,500 patients, with a goal of establishing safety. Rates of death, stroke, myocardial infarction and renal dysfunction are being measured between the Clevelox and other treatment groups. The comparative treatments are nitroglycerin, sodium nitroprusside and nicardipine.
Angiomax, the firm's revenue driver, was approved in the U.S. in late 2000 for patients undergoing percutaneous transluminal coronary angioplasty procedures.
In September, the European Commission granted the go-ahead to market Angiomax as Angiox in the member states of the European Union. The company had begun selling Angiox to Nycomed Danmark A/S, of Roskilde, Denmark, a European distribution partner, in August.
Total net revenue was $144.3 million in 2004, $85.6 million in 2003 and $38.3 million in 2002, and the firm achieved profitability on an annual basis for the first time last year, with net income of $17 million.
As of the end of last year, the company had about $161.2 million in cash and cash equivalents, available-for-sale securities and accrued interest receivable.