LONDON ¿ NeuroSearch A/S, of Glostrup, Denmark, said Pharmacia & Upjohn, of Bridgewater, N.J., has decided to terminate the license agreement on NS2710 for the treatment of generalized anxiety disorders, following assessment of the Phase IIa trial. The licensing deal began in July 1998.
The double-blind, placebo-controlled trial involved 124 patients, half of whom received NS2710 in a standard capsule formulation at a high dose. The trial showed a statistically significant improvement with NS2710 as compared to placebo, measured on the Hamilton Anxiety Scale (HAM-A). However, at this high dose of NS2710, sedation was observed ¿ which was expected, based on clinical Phase I data. Furthermore, a few cases of allergic reaction, possibly associated with the active compound, were seen.
NeuroSearch said it plans to evaluate the allergic reactions further and anticipates continuing the development of NS2710. It has a second development partner for the compound, Meiji Seika Kaisha Ltd., of Tokyo.
In 1993, NeuroSearch and Meiji Seika entered into an agreement on GABA modulators, including NS2710, under which Meiji Seika holds the rights to Japan and Asia, and NeuroSearch to the Nordic and Baltic countries of Europe. Following the termination of the agreement with Pharmacia & Upjohn, all rights to NS2710 will be returned to the two original partners who will hold jointly rights to the rest of the world territory.
More Brasofensine Trials Pending
NeuroSearch also gave an update on its collaboration with Bristol-Myers Squibb Co., of New York, for the development of brasofensine to treat Parkinson¿s disease. Last year, the partners carried out a four-week, placebo-controlled Phase II trial of brasofensine in patients recently diagnosed with the disease. Ninety-five patients were treated with brasofensine, and 55 patients given a placebo. The Parkinson¿s symptoms were assessed before treatment, and once weekly during the treatment, using the Unified Parkinson¿s Disease Rating Scale (UPDRS).
A preliminary evaluation of the results shows that while a 2-3 mg dose of brasofensine, administered once daily, resulted in a greater reduction of the UPDRS score than the placebo, the difference was only statistically significant in the evaluation after one week of treatment. NeuroSearch says a four-week trial is too short to demonstrate a significant anti-Parkinson¿s effect. However, a longer trial is not possible until further toxicological studies have been completed, because, as previously disclosed, in humans the treatment gives rise to a metabolite of brasofensine, which was not observed to the same extent in animal trials.
As a result of this finding, the FDA imposed a dosage restriction on brasofensine in any clinical trials conducted in the U.S. Elsewhere, clinical trials have been restricted to a treatment period of four weeks.
To date, brasofensine has been administered to a total of 192 Parkinson¿s patients and 122 human volunteers, with no serious adverse effects.
Two further clinical trials started in 1998. The first is in patients already undergoing medical treatment, but who have not developed dyskinesia ¿ the abnormal, involuntary movements that are a well-known side effect of existing treatments, and that brasofensine is believed to avoid. The second study is in patients who have developed dyskinesia while undergoing treatment. The results of these studies will be reported in mid-1999.
NeuroSearch said last week Bristol-Myers has notified the company that a decision will be made whether or not to continue the development of brasofensine following evaluation of these studies. n