For the second time in less than a month, cardiovascular drug company Nuvelo Inc. bolstered its portfolio through the acquisition of a clinical-stage product.
The Sunnyvale, Calif.-based company gained a worldwide license to an anticoagulant from Dendreon Corp. in exchange for a $4 million up-front payment, to be followed by additional fees. Nuvelo acquired recombinant nematode anticoagulant protein c2 (rNAPc2), a naturally occurring protein in a Phase IIa trial, to study its ability to block the Factor VIIa/Tissue Factor protease complex and all other rNAPc proteins.
"It's a beautiful fit with our pipeline," Nuvelo President and CEO Ted Love told BioWorld Today. "We have been trying to create the premier acute cardiovascular medicine franchise, so we've been particularly focused on hospital-based products. They have a synergy with a sales force we expect to build to sell [lead candidate] alfimeprase, and they have great synergy with the expertise and infrastructure that we've built within the company to develop these drugs. But they don't cannibalize each other's market."
He added that as acute-care products, their drug development path includes relatively quick trials with set endpoints, as well as less stringent safety guidelines given their one-time use in a hospital setting.
Nuvelo is making its initial payment to Dendreon in the form of cash and common stock, and the agreement provides for milestone payments and royalties upon commercialization of any rNAPc product candidates. More specific financial terms were not disclosed.
For Dendreon, the decision to divest the product stems from its oncology focus. The licensing arrangement allows the Seattle-based company to maintain rNAPc2's downstream potential through the possible royalty stream.
Nuvelo will own worldwide rights to all indications for rNAPc products.
Originally isolated from hookworms, rNAPc2's anticoagulant effect is the result of blocking the Factor VIIa/Tissue Factor mechanism responsible for beginning the blood clot-formation process. Nuvelo said that unlike aspirin, heparin and antiplatelet agents, which exert their effects at later stages of the blood-coagulation cascade, rNAPc2 blocks the first step in the clotting cascade, inhibiting coagulation before it starts.
A multicenter study began investigating the product's safety and efficacy in about 75 patients with acute coronary syndrome, a condition that usually occurs when an atherosclerotic plaque ruptures in one or more arteries of the heart, though Dendreon halted its enrollment. It acquired the drug through its $73 million purchase of San Diego-based Corvas International Inc., and at the time Dendreon made it clear that it planned to partner rNAPc2 down the road. Love said Nuvelo plans to complete the trial through the addition of 50 more patients, after which it will analyze the data and evaluate further clinical development directions. (See BioWorld Today, Feb. 26, 2003.)
"The first thing to weigh, quite frankly, is the probability that it will work," Love said. "We'll also weigh markets, and I don't mean that purely from a commercial perspective, but instead whether there really is an unmet medical need or is there a significant number of patients with the problem."
To date, rNAPc2 has been shown to be well tolerated in more than 500 patients and healthy volunteers in several Phase I and II studies. Love said bleeding has been the only side effect of note, adding that such an occurrence is expected in those patient populations.
A Phase II trial demonstrated that rNAPc2 appears to reduce the risk of developing deep-vein thrombosis and its related complications by more than 50 percent, compared to standard therapy for patients undergoing total knee-replacement surgery, without compromising safety. A second Phase IIa study demonstrated that rNAPc2 was well tolerated when added to standard therapy with unfractionated heparin, aspirin and clopidogrel in patients undergoing elective percutaneous coronary intervention. Its findings also demonstrated that rNAPc2 suppresses the formation of thrombin for at least 36 hours following a single administration, compared to standard therapy alone, in which thrombin generation continued unabated.
Other potential indications include uses of rNAPc2 in orthopedic and vascular surgery. Also, data published in The Lancet suggest rNAPc2 might be effective in treating the Ebola virus infection, while preclinical findings published in Cancer Research showed that blocking the protease complex Factor VIIa/Tissue Factor prevented the growth of primary and metastatic tumors in animal models.
Love said the company has yet to contemplate whether to move development forward on its own or with a development partner. Earlier this month, Nuvelo signed on as a partner to Archemix Corp. for ARC183, a thrombin inhibitor expected to enter Phase I development in the second half of this year. Cambridge, Mass.-based Archemix initially will lead development and maintain responsibility for all clinical development activities. Nuvelo can opt to lead commercialization efforts, in which both companies may participate.
The investigational product, which is characterized by short survival in the blood, will be evaluated for potential use in coronary artery bypass graft surgery, percutaneous coronary intervention and other acute anticoagulant applications. Nuvelo made an undisclosed up-front payment to Archemix, which also will be eligible for milestone payments, though the partners will split all development costs equally and have 50/50 ownership of the compound.
Beyond its latest additions, Nuvelo's pipeline includes the aforementioned alfimeprase, which remains in Phase II trials for both peripheral arterial occlusion and catheter occlusion. The company expects the peripheral arterial occlusion study to complete enrollment in a month or two, with plans to begin Phase III work in that indication in the second half of this year. Interim analysis in the catheter-occlusion study is expected by next month or April. The product is partnered with Thousand Oaks, Calif.-based Amgen Inc.
Dendreon's lead investigational candidate, Provenge, is a cancer immunotherapy in a pivotal Phase III trial for androgen-independent prostate cancer.
On Thursday, Nuvelo's stock (NASDAQ:NUVO) gained 1 cent to close at $5.24, while Dendreon's shares (NASDAQ:DNDN) dropped 53 cents to close at $13.30.