Pivotal work has gotten under way for cangrelor, an intravenous antiplatelet agent in development by the Medicines Co.
The Parsippany, N.J.-based company's first Phase III trial is expected to enroll a whopping 9,000 patients, followed by a 4,000-patient study to begin late this year. Both multinational trials - large because low event rates necessitate big numbers for statistical purposes - are designed to evaluate the fast-acting, reversible drug's ability to prevent platelet activation and aggregation during the clotting process.
"We think that I.V. cangrelor will provide superior platelet coverage," said Michael Mitchell, the company's executive director of corporate affairs, "which will lead to better outcomes"
Specifically, the studies will test the anti-clotting drug in preventing ischemic events in patients undergoing percutaneous coronary intervention (PCI), a catheter lab procedure to treat coronary artery disease. That acute setting is supported by Phase II findings published in last month's issue of the American Heart Journal, in which the authors described cangrelor's potential in treating acute coronary syndromes such as "those targeted for an early invasive strategy, in need of urgent percutaneous or emergent surgical revascularization, or in the case of vascular trauma."
The first trial, CHAMPION PCI, will test cangrelor against the standard treatment in that space, Plavix (clopidogrel, from Bristol-Myers Squibb Co. and the Sanofi-Aventis Group). The latter drug, which is delivered orally, has limitations because of its potential for bleeding complications in patients needing surgery after PCI - Plavix stays with a platelet for its remaining life, usually lasting several days, therefore delaying surgery. On the other hand, cangrelor's less-than-five-minute half-life means that a platelet "gets its activity back in less than an hour," Mitchell said, which frees physicians to move patients into an operating room, if need be, without fear of excessive bleeding.
The trial's primary endpoint is superiority at 48 hours, and patients may be treated with other intravenous anticoagulants, at the investigator's discretion. Cangrelor will be delivered at the beginning of the PCI procedure in a bolus, followed by further infusion. That route of administration is thought to be another advantage over Plavix, which is given in a high dose of up to eight tablets before PCI but takes several hours to kick in because of its need to metabolize in the liver. Also, cangrelor's IV delivery gives a physician more control than oral administration, especially in patients who could be partly sedated.
The second study, labeled Champion Platform, will measure cangrelor against placebo. The Medicines Co., which sees cangrelor as a centerpiece in its acute hospital care product franchise that already includes the anti-thrombin Angiomax (bivalirudin), expects enrollment to last 18 to 24 months.
"These studies are designed to show an improvement in the clinical outcome of a patient," Mitchell said, noting that the trials would watch for incidents such as deaths, myocardial infarction and revascularization.
Should cangrelor receive FDA approval, it could be the first marketed I.V. platelet inhibitor that binds directly to the P2Y12 receptor, the same target on which Plavix acts to treat or prevent arterial thrombosis in PCI patients. The company plans to internally commercialize the product in the U.S. and seek partners elsewhere. Analyst Liana Moussatos with Pacific Growth Equities LLC estimated annual peak sales topping $300 million for Cangrelor and has forecasted its potential launch at the end of 2009.
The Medicines Co. controls cangrelor's worldwide rights, save for a few Asian territories, via a December 2003 license agreement with AstraZeneca plc, of London. That deal involves milestone payments to AstraZeneca upon major market approval, followed by royalty payments. The Medicines Co. also paid an up-front fee for the product.
Down the road, the company might study its use in surgical settings. "There isn't any antiplatelet that a surgeon can use currently," Mitchell said.
Angiomax, the Medicines Co.'s approved acute hospital care drug, is marketed in the U.S. and other countries for use in patients undergoing coronary angioplasty. Sales of the anticoagulant totaled $150 million last year, and its profile recently received a boost at the American College of Cardiology meeting in Atlanta, where data showed it to be better than heparin in treating patients with acute coronary syndromes.
Analyst Moussatos predicted that Angiomax sales could receive a boost in the future with positive results from the Champion trial program and approval for cangrelor.
Also in late-stage development is clevidipine, an intravenous, short-acting calcium channel antagonist in Phase III for the short-term control of high blood pressure in hospital settings such as intensive care units or operating rooms. Pivotal work is scheduled to wrap up by the end of this year, with a new drug application planned for early next year.
On Tuesday, the company's stock (NASDAQ:MDCO) gained 11 cents to close at $20.17.