NS1209/SPD 502, A Novel Selective AMPA Antagonist for Stroke, Neuropathic Pain or Epilepsy? Drug Development Lessons Learned

Jan M Keppel Hesselink

Drug Dev Res. 2017 Mar;78(2):75-80.

PMID: 28195646


Preclinical Research The selective AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor antagonist, NS1209 (also known as SPD 502) has been explored in several research and development campaigns since its selection as a lead drug candidate in the early 1990s by the Danish biotechnology company, NeuroSearch. The compound was successively tested in animal models of stroke, neuropathic pain and epilepsy. The preclinical data to support development for the treatment of stroke were incomplete, as the compound was administered after the stroke episode, and did not protect subcortical areas of the brain. Preclinical data for neuropathic pain and epilepsy appeared more promising, but the design of the Phase IIa studies in both indications was suboptimal, and an exploratory study in neuropathic pain, like one in refractory epilepsy gave inconclusive results. Preclinical data in pain models were much less convincing than reported by the authors in abstract and discussion sections. Due to a long preclinical sequential testing phase and insufficiently powered clinical trials, NS 1209 disappeared from the CNS development pipeline, while its patent protection exclusivity was markedly reduced due to the unfortunate slow speed in development-a phenomenon far from unusual in CNS drug discovery. NeuroSearch ceased operations as an R&D entity in 2012 and its R & D portfolio was transferred to Teva Pharmaceuticals and to a spin off, Saniona A/S. Based on an in-depth case analysis of the development of NS 1209, a number of recommendations are given to reduce chances of failure during clinical development of neuropathic pain compounds and, more generally, of CNS compounds. Drug Dev Res 78 : 75-80, 2017. © 2017 Wiley Periodicals, Inc.

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