NitroMed Inc. entered a multiyear research collaboration with a subsidiary of Merck & Co. Inc. to develop nitric oxide-based medicines.

The collaboration leverages the Bedford, Mass.-based company's NitRx technology platform with Merck's research and development knowledge. Privately held NitroMed has developed a pipeline of nitric oxide-based molecules, as well as existing medicines enhanced with nitric oxide donors. While the companies have not disclosed specific details of the research, NitroMed's clinical focus areas include the treatment and prevention of cardiovascular and inflammatory diseases.

Particular financial details were not disclosed either, though Whitehouse Station, N.J.-based Merck will invest an undisclosed amount in NitroMed's research program. Specifically, the agreement secures multiyear funding for NitroMed scientists and equipment. Merck also will pay an up-front fee, certain research-based milestone payments and royalty payments.

Merck also will lend its commercialization expertise in the partnership.

"The company is really pleased to be partnered with one of the premier R&D-driven pharmaceutical companies in Merck," NitroMed CEO Michael Loberg told BioWorld Today. "From the moment that Merck approached us and began to look at our technology, we had the deal done in four months, which I think also speaks a little bit to our technology and its value."

The NitRx technology is designed to add the pharmacology of nitric oxide to the pharmacology of existing medicines.

"This is a way we take a good medicine and make it better," Loberg said. "And in the process, we create new intellectual property surrounding that medicine and give it a new patent life."

He said nitric oxide's therapeutic benefit stems from a number of factors - it is produced in endothelial cells, it is a vasodilator, it inhibits platelet aggregation and it has strong anti-inflammatory properties.

In addition to the Merck collaboration, NitroMed also is applying its technology in the area of drug-coated stents through an agreement with an undisclosed partner.

"You can imagine how nitric oxide could work to diminish the inflammation that accompanies the standing of the stent, and how it could also eliminate the platelet aggregation that sometimes occludes stents," Loberg said. "There's a host of ways that we can use nitric oxide to improve existing medicines."

NitroMed's most advanced product is BiDil, a combination drug containing isosorbide dinitrate and hydralazine hydrochloride designed to improve survival in African-Americans with heart failure. A pivotal confirmatory trial is continuing in 600 African-American men and women, with results expected early next year.

The trial, A-HeFT (African-American Heart Failure Trial), is being conducted with the assistance of the Association of Black Cardiologists and it monitors patients for survival, hospitalization and quality of life over a six- to 12-month period. NitroMed said A-HeFT is the first heart failure trial conducted exclusively in African-American patients.

Previously, BiDil was evaluated based on two large-scale vasodilator heart failure trials. Published analysis from both showed that BiDil provides a selective benefit to African-American patients with heart failure as compared to non-African-American patients receiving the drug. (See BioWorld Today, March 9, 2001.)

"An interim analysis in August was designed to test the hypothesis that BiDil would provide an outcomes advantage," Loberg said. "Indeed, the data were consistent with that hypothesis."

He said the analysis was based on the first 150 patients completing minimum follow-up requirements, with another interim analysis planned for March. The trial is scheduled to have enrolled 300 patients at that point.

NitroMed plans to develop BiDil on its own, but its business model features a partnering component, as evidenced by its latest agreement. For example, Loberg said the company is in partnering discussions for its program with COX-inhibiting nitric oxide donors.