LONDON - Glostrup, Denmark-based NeuroSearch AS, which is focused on central nervous-system disorders, has received approval to begin Phase II trials in the U.S. of NS2389 for the treatment of depression. President and CEO Jorgen Buus Larsen told BioWorld International that the efficacy trial of 150 patients at 10 centers will be completed in the third quarter of 1999.
NS2389 enhances the effect of three neurotransmitters: serotonin, dopamine and noradrenaline. This is in contrast to the existing widely used antidepressants fluoxetine (Prozac), paroxetine (Paxil) and citalopram (Celexa), all of which enhance the effect of serotonin alone. These drugs are effective in about 60 percent of patients and take three to six weeks to take effect.
"NS2389 should have a major advantage over selective serotonin antidepressants," Buus Larsen said. "Our preclinical and clinical tests have shown a more rapid onset of action, and a beneficial effect in more severe forms of depression, including patients who have suffered severe attacks of depression and for whom the only effective treatment to date has been electroconvulsive therapy."
While the time of onset of effect of NS2389 is yet to be established in clinical trials, Buus Larsen said university studies have shown the optimal effect was achieved within a week. "If we can show at least the same effect [as existing antidepressants], but a more rapid onset, this would reduce the risk of suicide."
According to Buus Larsen, eight pharmaceutical companies have expressed an interest in the compound. "We hope that, once the trial is up and running, we will send them information and will have a dialogue, allowing us to take on a partner before the next study," he said. The trial will compare placebo and a registered antidepressant with NS2389.
With sales of antidepressants totaling US$7.8 billion in 1997, in financial terms NS2389 is potentially the most important drug in the NeuroSearch portfolio. Buss Larsen said he hoped to conclude a deal which would give NeuroSearch an up-front payment, milestones and a royalty rate of over 10 percent. "Obviously this will depend on how competitive the profile turns out to be," he added.
NeuroSearch also expects to move into Phase III trials with brasofensine, an oral dopamine reuptake inhibitor for the treatment of Parkinson's disease, later in 1999. At present the Phase II trials, conducted in 1998 in collaboration with New York-based Bristol-Myers Squibb Co., are being analyzed. Research to date indicates that brasofensine is as effective as the existing treatment, L-dopa, without the serious side effect of dyskinesia.
"If we can show that brasofensine stabilizes the condition without dyskinesia, we might be on to an attractive track," said Buus Larsen.
NeuroSearch has a policy of taking compounds to the end of Phase IIa in order to increase their value and give the company more control over the speed of development. The company has about US$50 million cash, with a burn rate of US$10 million per annum, providing sufficient funds to move into profitability without raising more money.