AstraZeneca drops NMDA antagonist in stroke, refocuses on NXY 059

AstraZeneca has halted development of its neuroprotectant drugAR-R15896, which was in Phase II trials for the prevention of brain damage in acute ischemic stroke patients, reports the Financial Times. At its R&D meeting in December last year, the firm said that it planned to file for approval of AR-R15896 in 2002.

AR-R15896 is a non-competitive, low-affinity NMDA antagonist, which was thought to have advantages over other drugs in this class in terms of achieving relevant plasma concentrations and tolerability. It was designed to prevent the overexcitation of neurones during ischemia, which starves the tissue of oxygen and causes apoptosis of the nerve cell. However, a number of companies have terminated work on NMDA antagonists because of toxicity issues.

Despite this, Claes Wilhelmsson, R&D director at AstraZeneca, told the newspaper that AR-R15896 had not experienced problems in trials, rather that it was an issue of cost, noting that "cost limited the company's ability to move more than one candidate forward to Phase III clinical trials." AstraZeneca has two other compounds in the pipeline for acute ischemic stroke (and one already in pivotal trials), and has high hopes for one candidate, NXY 059, a free-radical trapping agent which is in Phase II clinical development under a license from Centaur Pharmaceuticals. NXY-059 traps reactive oxygen species (by a mechanism known as nitrone spin trap), and has been found to be well-tolerated when given by eight-hour infusion in Phase I studies.