Positive results from a Phase II study of MC-1 boosted Medicure Inc.'s stock Monday and offered promise that the small molecule could be used to reduce heart attacks in patients that undergo coronary artery bypass graft surgery.

Shares (TSE:MPH) climbed C28 cents, or 20.4 percent, on the Toronto Stock Exchange to close at C$1.65. In the U.S., shares (AMEX:MCU) rose 24 cents, or 20.2 percent, to close at $1.43.

The Phase II data fueled optimism not only among investors and patients, but also among clinical investigators and the company's management. MC-1, a purinergic receptor antagonist, represents Medicure's lead product and the second one, along with MC-4232, now ready to advance into Phase III trials. It has FDA fast-track status and has shown positive results in a prior Phase II trial, called MEND-1, in which it significantly reduced ischemic heart damage in patients undergoing percutaneous coronary interventions.

"MC-1's ability to protect the heart from injury has now been demonstrated in two Phase II studies," said Albert Friesen, Medicure's president and CEO, in a conference call. The latest results "support our belief that MC-1 will make a significant impact on saving lives following bypass surgery," he said, adding that "this study has exceeded our expectations and fully warrants the advancing of MC-1 into Phase III."

In this second Phase II trial, called MEND-CABG, a 250-mg dose of MC-1 resulted in a 14 percent reduction in the primary endpoint composite of death, non-fatal myocardial infarction and non-fatal stroke up to postoperative day 30 vs. placebo (p=0.312).

While MC-1 missed its primary endpoint, investigators were enthused by top-line results of another endpoint in which MC-1 at 250 mg showed a 37.2 percent reduction in death, non-fatal myocardial infarction and non-fatal stroke vs. placebo (p=0.028). The difference between the two had to do with the way myocardial infarction (MI) was defined. Since the trial was designed only to achieve a statistical trend, the primary endpoint used a low measure of MI, defining it by peak CK-MB levels being greater than or equal to 50 ng/ml. CK-MB is a cardiac enzyme that is released into the bloodstream by dying heart muscles. Increases in the enzyme help physicians to diagnose MIs.

But 90 percent of patients receiving CABG surgery have elevated levels of CK-MB, and investigators may have been "capturing things that aren't true events," Derek Reimer, Medicure's chief financial officer, told BioWorld Today.

Therefore, the company designed the trial to include a separate endpoint defining MI by a more standard measurement of peak CK-MB levels of greater than or equal to 100 ng/ml, "a level which has been used in previous Phase III trials," Reimer said. It was that definition that enabled MC-1 to achieve the 37.2 percent reduction in the composite endpoint. The percentage was driven largely by a 46.9 percent reduction in non-fatal MI vs. placebo (p=0.008).

And by taking the CK-MB measure completely out of the equation, investigators found that the 250-mg dose, which notably had greater efficacy than the 750-mg dose, resulted in a 78.7 percent reduction in physician-diagnosed MI vs. placebo (p=0.0065).

The MEND-CABG trial enrolled 901 patients at 42 sites in Canada and the U.S. The primary endpoint evaluated the effect of MC-1 at postoperative day (POD) 30, while secondary endpoints evaluated the product at POD four and 30, and will evaluate it again at POD 90. Other secondary endpoints included cardiac tissue damage as determined by CK-MB and neurological function. Medicure has not disclosed the full results, including safety and tolerability data, but intends to do so upon completion of POD 90 data, presenting the findings at a scientific meeting or by publication in the coming months.

The top-line data of MC-1 led investigators to conclude that a Phase III trial design likely would use a 250-mg dose to evaluate the drug's effect on death and non-fatal MI in CABG surgery patients, measuring the incidences of MI with the 100 ng/ml CK-MB threshold. They also might choose to again include non-fatal stroke in the composite endpoint, though the limited number of cases in the Phase II trial indicate it may not be necessary.

A Phase III trial is expected to start in the coming third quarter, and take between 12 and 18 months to complete, meaning MC-1 could reach the market in late 2008 or early 2009. Reimer said it could be a $500 million drug for Medicure since CABG is "one of the most frequently performed surgeries right now in North America," and there is no therapy that currently "addresses this ischemic damage that develops as a result of the surgery."

A naturally occurring small molecule, MC-1 appears to reduce the amount of damage to the heart following ischemic or ischemic reperfusion injury by protecting cardiomyocytes, or heart muscle cells, which are important for normal heart function and do not regenerate following an ischemic event. Preserving them is important in the maintenance of proper heart function.

Medicure is actively looking for a partner for MC-1. As the company enters a much larger, Phase III study, it hopes to have the "muscle power of a large pharmaceutical company to promote the product," Reimer said.

Medicure, of Winnipeg, Manitoba, also has its MC-4232 product slated to begin a Phase III trial about the same time that MC-1 does. That product is a combination of MC-1 and the ACE inhibitor, lisinopril, and is being developed for patients with diabetes and hypertension. Phase II data have demonstrated MC-4232's antihypertensive, hypoglycemic and lipid-lowering properties.