BioWorld International Correspondent

NeuroSearch A/S and GlaxoSmithKline plc shelved the development of NS2359 in attention deficit hyperactivity disorder (ADHD), following an interim analysis of a Phase II trial that showed the compound did not meet its primary endpoint.

They now plan to pursue development of the drug in depression. A Phase II trial in that indication is planned for next year.

In the ADHD trial, 126 adult patients received either 0.5 mg per day of NS2359 or placebo over an eight-week treatment period. Those receiving drug exhibited significant improvements in concentration, attention and memory, as measured by the Cognitive Drug Research system, a computer-based, objective scoring method. However, the drug failed to attain its primary endpoint, based on a subjective assessment of ADHD symptoms.

"We had a very clear effect on this CDR test system, but not a clear and significant effect on other symptom scores," said J rgen Buus Lassen, CEO and president of Ballerup, Denmark-based NeuroSearch.

He said the negative results do not have implications for NS2359 in depression. Subjects enrolled in the ADHD study were required to have a Hamilton rating of less than 10, whereas those with severe depression have a score of 20 to 30.

"When they entered the deal with GlaxoSmithKline, it was obvious GSK had greater interest in depression," said Annette Rye Larsen, analyst at HSH Gudme in Copenhagen, Denmark. That indication has greater market potential than ADHD anyway, and GSK already has an existing drug franchise in the area. "Still, if the data had been good, I think they would have pursued the ADHD indication," she said.

The ADHD study was under way before London-based GSK entered the alliance in December with NeuroSearch, which included NS2359. Lassen said that it always had been GSK's intention to obtain "meaningful" clinical information in depression before pursuing any additional indications with the compound.

The triple monoamine reuptake inhibitor's potential is based on several physiological effects. The compound acts by boosting levels of the monoamine neurotransmitters dopamine, noradrenaline and serotonin. More recent evidence indicates that it also appears to enhance the activity of acetylcholine in areas of the brain linked to cognitive functions. Existing antidepressants, Lassen said, have either a neutral or a negative effect on that parameter.

"We have in our preclinical models some other effects, which potentially could also be used clinically," he said. Those additional data have not been disclosed.

NeuroSearch also reported progress from its lead program, NS2330, which is in development for both Parkinson's disease and Alzheimer's disease. Its partner, Boehringer Ingelheim GmbH, of Ingelheim, Germany, completed enrollment in Phase II trials in each indication. Results from those studies, which involve a total of 930 patients, are expected during the first half of next year, and decisions on Phase III trials will be made over the summer.