Once-Promising Stroke Drug Fails in Trial

NXY-059 is a member of a chemical family whose brief designation is PBN, Proctor said. That PBNs have a strong tendency to "hydrolyze" -- react chemically with water -- is well known, he said. Proctor contends that the breakdown products of hydrolysis reactions produce the beneficial effects of NXY-059.

NXY-059 has a completely different action than tPA, which reduced brain damage by dissolving a clot that blocks a brain artery. Instead, NXY-059 protects brain cells by trapping free radicals, inflammatory cells that are generated in a blocked artery. "It is the hydrolysis products that are biologically active," Proctor said.

There could well have been less hydrolysis in the drug used in the second trial than that used in the first, he said.

AstraZeneca, the pharmaceutical company that's developing NXY-059 as a stroke treatment, obtained a patent between the two trials on a method of stabilizing the molecule by certain methods -- including preventing hydrolysis in the compound, Proctor said. Thus, it is possible that patients in the two trials received versions of the drug different enough to account for the conflicting results, he said.

When he tried to present that idea to AstraZeneca officials, "they wouldn't talk to me," Proctor said. But he acknowledged that he is in a patent battle that pits him against the drug company. Proctor said he holds patents on the medical use of hydrolysis products of PBN chemicals.

However, study co-investigator Leyden said AstraZenecadidinvestigate Proctor's claim. "They took the allegation very seriously, did the testing, and said they were confident there was no breakdown product involved," he said.

In the meantime, Proctor said a paper written by him, describing the proposed beneficial effects of PBN-linked hydrolysis reactions, has been accepted by the journalStrokeand will be published in that journal in September.

AstraZeneca did not respond immediately for a comment on the paper.

More information

There's more on current stroke treatments at the American Heart Association.

SOURCES: Kennedy R. Lees, M.D., professor, cerebrovascular medicine, University of Glasgow, Scotland; Peter H. Proctor, M.D., Ph.D., Houston, Texas; Patrick Leyden, M.D., director, University of California, San Diego/Veterans Administration Stroke Center; Aug. 9, 2007,New England Journal of Medicine