Why do neuroprotective drugs that are so promising in animals fail in the clinic? An industry perspective

1. No neuroprotective drug has yet been shown to be effective in treating acute ischaemic stroke in the clinic, despite evidence of efficacy in animal models. 2. An academic/industry round-table group recently published guidelines to be met if a drug was to be progressed to clinical trial. 3. Major points included obtaining full dose-response evaluation and measurement of the therapeutic time window for efficacy, functional behavioural testing in addition to measurement of infarct volume, measurement of physiological parameters, use of appropriate models (transient and permanent focal ischaemia) and reproducibility of data by external laboratories. 4. The present paper examines both failed compounds and disodium 4-[(tert- butylimino) methyl] benzene-1, 3-disulphonate N-oxide (NXY-059), a nitrone radical-trapping agent currently in clinical development. It aims to determine whether these guidelines were met by compounds that have failed and, thus, determine whether following the guidelines, as is being done with NXY-059, will increase the chances of developing efficacious drugs for treating acute ischaemic stroke. 5. It is concluded that we will only achieve the goal of producing a clinically effective neuroprotective agent if the guidelines have been met by the novel compound under investigation.