Shares of cash-strapped Medicure Inc. plunged 85 percent Monday after the firm said its lead product MC-1 failed to meet its primary endpoint of reducing the incidence of cardiovascular death or nonfatal myocardial infarction following coronary artery bypass graft (CABG) surgery.
Shares (AMEX:MCU) closed at 12 cents Monday, a drop of 68 cents.
Based on the Phase III results, the Winnipeg, Manitoba-based firm is indefinitely postponing its submission of a U.S. approval application for MC-1 for the CABG indication, CEO Albert D. Friesen said Monday during a conference call.
The analysis of MEND-CABG is ongoing, and details of the study results will be presented at the late-breaking clinical trial session of the American College of Cardiology (ACC) in Chicago on April 1, Friesen told investors and analysts.
Because of ACC's embargo rules for late-breaking clinical trials, he noted, the firm was unable Monday to provide any further details of the study results.
Friesen took no questions during the conference call.
"Although we are clearly and extremely disappointed in the study outcome, I believe that the MEND-CABG II study was executed in an efficient and well-executed manner," he said.
"The study design and the protocol for MEND-CABG II were developed with internationally recognized opinion leaders in both interventional cardiology and cardiothoracic surgery," Friesen noted.
The pivotal Phase III MEND-CABG II trial, initiated in November 2006 under an FDA special protocol assessment, was a double-blind, randomized, placebo-controlled clinical trial that enrolled more than 3,000 patients undergoing CABG surgery at more than 130 cardiac surgical centers throughout North America and Europe.
Study patients were randomized to receive placebo or MC-1 250 mg before surgery and for 30 days postoperatively. Study participants were followed for 60 days after treatment, or 90 days postoperatively, for additional safety and efficacy analysis.
Medicure conducted the MEND-CABG II study in conjunction with Duke Clinical Research Institute (DCRI) and Montreal Heart Institute.
The results of the study, said analyst Joseph P. Schwartz, of Leerink Swann, "must be clearly outside the scope of the company's special protocol assessment, since MCU does not plan on submitting an NDA to the FDA."
Schwartz wrote in a research note that his firm had downgraded Medicure to market perform from outperform.
John Alexander, associate professor of cardiovascular medicine at DCRI and a member of the MEND-CABG II study steering committee, said he shared in Medicure's disappointment in the outcome of the study.
Nonetheless, he said, "we've answered an important question, and I commend their company for their commitment to investigating such a difficult area. Ischemia reperfusion injury is a serious problem during cardiac surgery and other common cardiac interventions and Medicure's research in this area will only serve to enlighten us more."
The outcome of MEND-CABG II trial, Friesen said, "serves as a reminder that clinical studies at all phases have inherent risks."
Nevertheless, he said, "we believe we developed MC-1 with a very good step-like approach, completing two acute phase studies in well-run trials before proceeding to this important pivotal study for registration."
With the analysis of the Phase III study still ongoing, Friesen said, "it is premature to say without full certainty that Medicure will seek MC-1's acute development for CABG."
After the Phase III MC-1 "road bump," he said, if Medicure makes any future investments in the compound, it would be as a chronic application for hypertension, diabetes and dyslipidemia.
The company recently announced positive Phase II results of its combination product of MC-1 and the ACE inhibitor lisinopril in patients with coexisting diabetes and hypertension.
"As we all know, diabetes is a huge and a growing market and where MC-1 has already shown very good promise," Friesen said.
The firm also is developing MC-4262, a combination product using MC-1 and an angiotensin-receptor blocker to treat hypertension in patients whose condition is complicated by metabolic syndrome resulting in increased cardiovascular risk.
The firm plans to "aggressively explore" collaborations that will allow it to continue to develop MC-1 in chronic applications, Friesen said.
Although the outcome of MEND-CABG II is "clearly a setback" for the company, he said, "we remain focused on our core objective of developing novel cardiovascular drugs for the improvement of health of all patients."
Friesen noted that Medicure has one commercial cardiovascular product, Aggrastat (tirofiban hydrochloride), a drug used in combination with heparin for the treatment of acute coronary syndrome, including patients who are to be managed medically and those undergoing percutaneous transluminal coronary angioplasty or atherectomy.
Medicure acquired the rights to Aggrastat in August 2006 from Minneapolis-based MGI Pharma Inc. Whitehouse Station, N.J.-based Merck & Co. Inc. owns the marketing rights for the drug outside the U.S.
Medicure will focus investment on Aggrastat and explore options to maximize its value, Friesen said.
The firm also plans to significantly reduce its burn rate, "with the greatest savings anticipating in our clinical costs," he added.
Medicure has cash until near fiscal year-end, "but we are now terminating our MC-1 new drug application process and its related contracts and agreements, which should provide substantial savings and extend our cash position for several months beyond this fiscal year," Friesen said.
"We will evaluate various financial options in the coming weeks and months and provide more guidance as appropriate," he noted.