Medicure Inc. began enrolling patients in its pivotal Phase III study of MC-1, a cardioprotectant aimed at reducing heart attacks in patients undergoing coronary artery bypass graft (CABG) surgery.

Designated MEND-CABG II, the double-blind, randomized, placebo-controlled trial is expected to involve about 3,000 patients at 120 cardiac surgical centers in North America and Europe. Patients will receive either MC-1, administered at 250 mg, or placebo prior to surgery and for 30 days following surgery, and the primary endpoint will measure the reduction in the composite cardiovascular death and nonfatal myocardial infarction up to postoperative day (POD) 30.

Medicure still is in discussion with the FDA regarding specific protocol, but the overall trial design is expected to be similar to the previous 901-patient Phase II MEND-CABG study, with a couple of exceptions.

"The biggest change is in the primary endpoint," said Dawson Reimer, vice president of operations for Medicure. While the Phase II study measured the reduction in composite death, myocardial infarction and stroke at POD 30, the pivotal trial will look "only at death and myocardial infarction."

That's because MC-1's mechanism does not appear to be antithrombotic, and therefore, the drug's impact on stroke is not an efficacy focus, Reimer said. The pivotal study also revises the definition of myocardial infarction to a measurement of peak CK-MB levels of greater than or equal to 100 ng/ml, rather than the 50 ng/ml used in the Phase II trial. That puts it in line "with the FDA's expectations," Reimer said, "and with what is the standard in this kind of setting."

CK-MB is a cardiac enzyme released into the bloodstream by dying heart muscles. In the Phase II study, MC-1 missed its primary endpoint under the 50 ng/ml CK-MB assessment, but demonstrated a 46.9 percent decrease in the incidence of nonfatal myocardial infarctions when the peak CK-MB was at 100 ng/ml or greater. (See BioWorld Today, Dec. 6, 2006.)

Reimer said pivotal trial enrollment is expected to take about a year. Following treatment, patients will be followed for an additional 60 days for further safety and efficacy analysis.

Pending positive results, the Winnipeg, Manitoba-based firm expects to file a new drug application for MC-1, which has fast-track status in the U.S., with a market launch expected in late 2008 or early 2009. If approved, MC-1 would become the first cardioprotectant drug for patients undergoing CABG surgery, a procedure that's performed about 500,000 times yearly in the U.S. but still carries risks, including perioperative ischemia, inadequate myocardial protection and reperfusion injury. MC-1, a naturally occurring small molecule, aims at protecting cardiomyocytes, or heart muscle cells, which are not capable of regeneration following an ischemic event.

At this time, Medicure holds all rights to the product. "Our intent was to take it as far as we can on our own," Reimer told BioWorld Today, though he added that the company anticipates to seek "at minimum, a marketing partner for North America and a more substantial marketing partner for places like Japan and Europe."

Last month, Medicure launched a 20-person U.S. acute cardiovascular sales force that initially would market Aggrastat, an approved glycoprotein IIb/IIIa inhibitor for acute coronary syndrome. The company gained U.S. rights to Aggrastat from Minneapolis-based MGI Pharma Inc. in August, in exchange for $19 million and fees for existing inventory. Medicure also agreed to pay royalties to Aggrastat developer Whitehouse Station, N.J.-based Merck & Co. Inc. (See BioWorld Today, Aug. 10, 2006.)

That sales force also is being "built to carry some of the load of marketing MC-1," Reimer said.

Beyond MC-1, Medicure has a second late-stage product in its pipeline, MC-4232. That drug is designed as a combination of MC-1 and lisinopril, an ACE inhibitor, to treat diabetic patients with hypertension. That product has completed Phase II, and the company anticipates starting a Phase III program in the coming year, Reimer said.

Shares of Medicure (AMEX:MCU) closed Friday at $1.40, down 2 cents.

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