Staff Writer

Nuvelo Inc. took the first step in getting its alfimerprase development program back on track as it began enrollment in the previously discontinued SONOMA-3 trial.

The open-label, single-arm trial will use a higher dosage of alfimerprase than was used in the failed SONOMA-2 Phase III trial, which also was for treating central venous catheter occlusion. That setback in December was accompanied by the failure of alfimerprase in a separate Phase III trial in acute peripheral arterial occlusion.

Since then, Nuvelo lost its partner for the thrombolytic agent, a recombinant, direct-acting fibrinolytic, but officials there were encouraged enough to decide to continue development on their own.

The SONOMA-3 trial will evaluate safety and efficacy of a single 10-mg dose of alfimeprase with a concentration of 5 mg per milliliter in up to 100 patients. The primary efficacy endpoint is restored catheter function within 15 minutes. The failed study used a 3-mg dose with a concentration of 1.5 mg/ml.

Data from the trial are expected in 2008, and if positive, could support a full Phase III program in catheter occlusion. A Phase II trial in the larger indication of stroke is expected to start this year, while Nuvelo has moved back to preclinical development in peripheral arterial occlusion to optimize delivery in that indication.

The company in August announced a restructuring program that laid out plans for development of alfimerprase and two early stage products, NU206 and NU172, while suspending development of its rNAPc2 programs. The restructuring also included a headcount reduction of about 30 percent, bringing Nuvelo to fewer than 80 employees.

"We have a lot of interesting programs ahead of us, and a lot of execution that needs to happen," said Nicole Foderaro, a spokeswoman for Nuvelo. "We'll be starting stroke soon, we are up and running in catheter occlusion, and we have the preclinical programs. We have a lot going on, and we need to make sure we get the story out there and people understand," she told BioWorld Today. "We are still moving forward. We have the cash on hand, the programs and the people."

The failed SONOMA-2 trial in catheter occlusion actually did demonstrate restoration of catheter function, with a "p" value of 0.022. The trial, however, was designed to show a higher level of statistical significance.

Company officials said that although thrombolytic activity was seen, it was not enough to translate into commercial success.

Former partner Bayer Healthcare AG has backed out of its alfimerprase collaboration with Nuvelo since the failed trials in December, and it was in June that Nuvelo disclosed its intention to move forward on its own. (See BioWorld Today, Dec. 12, 2006, and June 28, 2007.)

Nuvelo had $120.2 million in cash as of June 30, a total that did not include $15 million due from Leverkusen, Germany-based Bayer related to termination of their deal. Foderaro said the money on hand was expected to provide more than two years of operating cash.

Bayer retained a one-time option to opt back into the collaboration, which began in January 2006 and gave Bayer rights to the product outside the U.S. Nuvelo got $50 million up front in that potential $385 million deal. Bayer's option to get back in the program would come at the time Nuvelo initiates a pivotal Phase III trial in stroke. The option covers all indications, not just stroke, Foderaro said.

In addition to the SONOMA-3 trial and the upcoming CARNEROS-1 trial in stroke, Nuvelo intends to move NU172, an antithrombin aptamer, into the clinic later this year or early next year. Its other preclinical product, NU206 (R-spondin1), is a recombinant, secreted protein designed to stimulate gastrointestinal epithelial cells. Target indications include inflammatory bowel disease and mucositis.

Nuvelo's stock (NASDAQ:NUVO) had fallen 79.3 percent, to $4.05, in December when it reported the negative Phase III data. The shares gained 27 cents Wednesday to close at $1.90.