BioWorld International Correspondent
The antidepressant drug development alliance between Danish firm NeuroSearch A/S and partner GlaxoSmithKline plc has hit a bump that will delay progress by several years. The two companies have decided to discontinue development of the neurotransmitter reuptake inhibitor NS2389, which had been in Phase II clinical trials.
They are working on three alternatives, one of which will go forward into preclinical development. “We are very near to selecting one of them now,” NeuroSearch President and CEO Jorgen Buus Lassen told BioWorld International. The replacement compound should be chosen before the end of the second quarter, he said.
NeuroSearch had selected NS2389, which blocks reuptake of the three monoamine neurotransmitters serotonin, noradrenaline and dopamine as a potential substitute for currently available serotonin reuptake inhibitors. The Ballerup-based company aims to develop a drug with faster onset of activity and a better patient response profile. It entered a deal with London-based GlaxoSmithKline worth a potential US$57 million, plus royalties, in January 2000. (See BioWorld International, Jan. 26, 2000.)
The Phase II trial was suspended the following June, however, because of negative data emerging from animal studies. Since then, further animal toxicology work has uncovered cell changes occurring in experimental animals that have received high doses of NS2389 over a long-term period.
“It is some kind of hyperplasia occurring at very high doses,” Buus Lassen said. The effect was not observed in the 217 human participants in Phase I and Phase II studies.
The partners have been unable to work out the mechanism underlying the high-dose phenomenon. Moreover, its extent has varied among different species. For those reasons, they decided that developing an alternative offered a better bet.
“It was a difficult decision but we thought the risk [was] simply was too high,” Buus Lassen said. The company may not have been able to submit a dossier demonstrating better safety and efficacy compared to existing treatments.
This reversal still leaves NeuroSearch with five compounds in the clinic, including NS2330 for Alzheimer’s disease and Parkinson’s disease; NS2359 for cocaine addiction; and NS2710 for anxiety. They are in Phase II studies, while NS1209, a treatment for brain damage following stroke and epilepsy, and a sickle cell anemia treatment, NS3728, are at the Phase I stage.