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Bivalirudin Supplemental NDA Submitted to FDA

PARSIPPANY, N.J., Aug 4, 2003 (BUSINESS WIRE) -- The Medicines Company (Nasdaq: MDCO) today announced that it has submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) seeking an amended Angiomax(R) (bivalirudin) product label in percutaneous coronary intervention (PCI). Angiomax was approved in the U.S. in December of 2000.

The Company submitted data from studies in more than 7,000 patients undergoing coronary angioplasty in the REPLACE-1 and REPLACE-2 trials, and the ATBAT study in angioplasty patients with heparin-induced thrombocytopenia and thrombosis syndrome, or HIT/HITTS. HIT/HITTS is a clinical condition caused by heparin, a family of products manufactured from by-products of cow lungs or pig intestines that carries multiple clinical and practical limitations. HIT/HITTS is characterized by reduced platelet counts and potentially widespread, life-threatening blood clots.

"Angiomax has been evaluated in clinical studies in a wide range of patients from elective to acute treatment, with stable and unstable coronary disease, with different types of stents, and with several combinations of concomitant pharmaceutical products," said Clive Meanwell, Executive Chairman of The Medicines Company. "We have invested aggressively in Angiomax Phase 3 and Phase 4 clinical programs because we expect to expand the use of Angiomax by demonstrating its superiority to heparin."

The REPLACE program evaluated the use of Angiomax as a replacement for heparin in patients undergoing coronary angioplasty with stents, and with concomitant pharmaceuticals such as clopidogrel and GP IIb/IIIa inhibitors. REPLACE-1 evaluated Angiomax safety and effectiveness when used with clopidogrel and GP IIb/IIIa inhibitors routinely, with GP IIb/IIIa inhibitors used in 70% of the patients. REPLACE-2 evaluated Angiomax use with recommended clopidogrel and provisional use of GP IIb/IIIa inhibitors.

REPLACE-2 results, published in the Journal of the American Medical Association (JAMA), demonstrate that the anticoagulant regimen built on Angiomax with provisional (7.2 % of patients) GP IIb/IIIa inhibitor use is superior to heparin alone for both efficacy and safety endpoints. Similarly, when the regimen built on Angiomax was compared to a study arm that included heparin plus GP IIb/IIIa inhibitors, the Angiomax arm was found to be as effective, while easier to use, safer and less costly. The study was also conducted to evaluate an Angiomax dose that The Medicines Company intends to revise with the supplemented label, if approved.

Mandated by the FDA, the ATBAT study will provide a new indication for Angiomax in patients undergoing PCI with HIT/HITTS if results are accepted and approved. Approximately one to three percent of patients who have received heparin experience HIT/HITTS. The underlying mechanism for HIT/HITTS appears to be an immunological response, which results in thrombocytopenia, or lower platelet counts, and in some cases in arterial or venous clotting. The clotting may result in death or the need for limb amputation. Because further administration of heparin is not possible in patients with HIT/HITTS, an alternative anticoagulant is necessary in order to provide anticoagulation for coronary angioplasty.

The Medicines Company separately announced today that it submitted a Market Authorisation Application (MAA) to the European Agency for the Evaluation of Medicinal Products (EMEA) for Angiomax use in PCI.

About Angiomax
Angiomax is a synthetic product currently approved in the U.S., New Zealand, Canada, Argentina and Israel for use in unstable angina patients undergoing coronary angioplasty. Angiomax is a direct thrombin inhibitor with a naturally reversible mechanism of action. In clinical trials, Angiomax has shown a reduction in the incidence of death, myocardial infarction, and the need for revascularization in patients undergoing coronary angioplasty, as well as significant reductions in bleeding complications compared to heparin, or heparin plus a GP IIb/IIIa inhibitor in the contemporary catheterization lab setting. These reductions in ischemic and bleeding complications are consistent and remain evident in high-risk patients unlike outcomes in high-risk patients treated with heparin. Reductions in these complications represent not only the opportunity for better patient care, but also the opportunity for cost savings.

Angiomax is indicated for use as an anticoagulant in patients with unstable angina undergoing percutaneous transluminal coronary angioplasty (PTCA). Angiomax is intended for use with aspirin. The most common adverse events for Angiomax in clinical trials comparing Angiomax and heparin were back pain, pain, nausea, headache, and hypotension. The incidence of these adverse events was comparable in both the Angiomax and heparin groups. An unexplained fall in blood pressure or hematocrit, or any unexplained symptom, should lead to serious consideration of a hemorrhagic event and cessation of Angiomax administration. Angiomax is contraindicated in patients with active major bleeding or hypersensitivity to Angiomax or its components. Please see full prescribing information available at

Source: The Medicines Group

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