West Coast Editor

Amgen Inc. opted for a license arrangement rather than an equal partnership with Nuvelo Inc. for the Phase III-ready clot-dissolver alfimeprase, the lead product candidate that is the subject of a deal started almost three years ago.

Wall Street took the news calmly. Nuvelo's stock (NASDAQ:NUVO) closed at $9.07, down 15 cents.

"It had been discussed in the investment community for a while as a potential buying opportunity," given likely weakness in the stock if Amgen chose licensing, said Liana Moussatos, an analyst with Pacific Growth Equities in San Francisco. But when it happened, she realized "it was going to be a five-minute buying opportunity."

"Nuvelo did a good job of explaining it to The Street up front," she told BioWorld Today, and the investors were being braced for alfimeprase news in the company's third-quarter earnings call, originally slated for Nov. 1 but moved to Nov. 9.

Amgen, Moussatos said, simply chose not to develop a sales force in the acute cardiovascular area.

"We've seen the Phase II data and they're great," she added. Moussatos owns no Nuvelo stock, but her firm makes a market in the company and seeks to do investment banking for it.

Alfimeprase, a derivative of the fibrolase enzyme, was discovered by Amgen and is being developed to treat peripheral arterial occlusions (PAO), with Phase III trials expected to begin in the first quarter of next year.

Acute PAO, also known as "leg attack," strikes more than 100,000 in the U.S. every year and involves the blockage of arterial blood flow to the lower limbs by a clot. The trouble often develops at sites of underlying atherosclerotic peripheral arterial disease, and the classic early symptom of leg attack is leg pain. If untreated, the condition can lead to ulcers, gangrene, tissue death and amputation of the foot or leg.

Under the terms of the 2002 deal, Amgen had the option to collect milestone payments and royalties rather than split expenses and profits, and has decided to go that route. (See BioWorld Today, Jan. 10, 2002.)

Two Phase III studies, which may overlap, are included in the 700-patient program endorsed by the FDA. The primary endpoint is the avoidance of open vascular surgery at 30 days, with secondary endpoints to include restoration of arterial blood flow and increase in ankle brachial index (blood pressure).

The Phase III effort is expected to take as long as two years, followed by a 10-month FDA review and, if all goes well, launch in the fourth quarter of 2007. Talks are ongoing with the agency regarding a special protocol assessment.

Sunnyvale, Calif.-based Nuvelo was formed by way of a merger completed early in 2003 by Hyseq Pharmaceuticals Inc., also of Sunnyvale, and Variagenics Inc., of Cambridge, Mass. (See BioWorld Today, Nov. 12, 2002.)

With $80 million in cash as of its last quarterly report (for the period ending June 30), Nuvelo also has recombinant nematode anticoagulant protein c2 (rNAPc2), acquired from Seattle-based Dendreon Corp. in exchange for a $4 million up-front payment, to be followed by potential milestone and royalty fees. The product is in a Phase IIa trial for use in treating acute coronary syndromes including unstable angina and non-ST segment elevation myocardial infarction. (See BioWorld Today, Feb. 6, 2004.)

Also at the start of the year, Nuvelo entered a worldwide collaboration with Archemix Corp., of Cambridge, Mass., to develop and commercialize ARC183, a thrombin inhibitor for use in coronary artery bypass graft and percutaneous coronary intervention. The drug, a DNA aptamer, entered Phase I trials in August.

"They've been preparing for this," Moussatos said, regarding Amgen's decision related to alfimeprase. "They filed a big shelf [registration] a couple of months ago, and they did a line of credit, so they'll probably raise money" to push the compound along.

"I think they'll do fine by themselves," she added, but probably will seek a partner for marketing outside the U.S.

Thousand Oaks, Calif.-based Amgen's shares (NASDAQ:AMGN) ended the day at $54.99, down 68 cents.