By Debbie Strickland

The Medicines Co. has been in business just 16 months and has yet to conduct a clinical trial, yet the firm has filed its first new drug application (NDA) with the FDA, for Hirulog, an anticoagulant licensed from Biogen Inc.

Cambridge, Mass.-based Medicines is seeking approval for the drug — the only one in its portfolio — for use in patients with unstable angina undergoing percutaneous transluminal coronary angioplasty.

Hirulog (bivalirudin) is a direct thrombin inhibitor derived from hirudin, a natural anticoagulating enzyme secreted by leeches.

Four years ago, Biogen discontinued development of Hirulog when the drug failed to achieve statistical significance in Phase III trials for preventing cardiac complications associated with angioplasty. Biogen, also of Cambridge, noted the drug performed well in certain patient subgroups.

Results released at the time, along with those subsequently published in the New England Journal of Medicine in 1995, were preliminary.

"Biogen did design and oversee the clinical trials that were the basis for the submission," said Peyton Marshall, Medicines' chief financial officer. "After acquiring Hirulog, The Medicines Co., together with our partners at Quintiles [Transnational Corp., of Research Triangle Park, N.C.] analyzed the data according to protocol specifications."

The final analysis, he said, "supports the view that Hirulog improves the benefit-to-risk relationship for patients receiving anticoagulation for angioplasty."

Though the NDA is based on Biogen trials, Medicines plans to launch two Phase III trials this year, one in angioplasty and one, described as "substantial," in myocardial infarction. A Phase II trial comparing Hirulog with heparin showed that Hirulog was significantly more effective in restoring coronary blood flow following heart attack.

Medicines also is aiming to "reduce manufacturing costs substantially," said Marshall.

With its first drug now at the FDA, Medicines, whose business model centers on in-licensing, is casting for new candidates.

"We are looking at other alternatives and are in active discussions with other companies," said Marshall, "but at this point there is nothing firm."

Medicines acquired Hirulog in March 1997 from Biogen in a licensing deal worth up to $30 million, including upfront fees, milestone payments, development commitments and royalties. *