Phase II study with NR2B sub-type selective NMDA antagonist in treatment-resistant depression voluntarily terminated


Hamburg, Germany - 18 May 2011: Evotec AG (Frankfurt Stock Exchange: EVT, TecDAX) and Roche (SWX: RO, ROG; OTCQX: RHHBY) today decided to voluntarily terminate the first proof-of-concept study in treatment-resistant depression with their NR2B sub-type selective NMDA antagonist EVT 101.

The decision to terminate this Phase II study was triggered by difficulties to recruit patients under the current study protocol, resulting in the possibility of inconclusive results. EVT101 was generally well tolerated in healthy volunteers and patients enrolled so far. Difficulties in conducting this Phase II study in treatment resistant depression, the need to sharpen the toxicology profile and a potential requirement for an altered dosage scheme lead to an overall delay in the programme. Based on this, the parties concluded to terminate the clinical development.

This clinical development has been the key part of an alliance between Evotec and Roche in which Roche has provided all funding in exchange for certain option rights after a proof-of-concept result with NR2B sub-type selective NMDA antagonist in treatment-resistant depression.

Evotec retains all rights in the EVT100 series, especially the back-up compound EVT103, and will enter into partnering discussions for these assets in another clinical development partnership. As advanced clinical development of drug candidates is not part of Evotec's core business, Evotec does not intend to pursue further clinical development of its NR2B sub-type selective NMDA antagonist without a partner. 

About NMDA receptors in treatment-resistant depression and EVT 101

NMDA receptors are involved in the pathology of depression and other CNS diseases. NR2B-selective antagonists bind preferentially to the activated form of the NMDA receptor containing the NR2B subunit and allosterically modulate, in an activity-dependent manner, channel activity by inhibiting channel opening probability. They show advantages over non-selective NMDA antagonists due to greater separation of efficacy from side effects. The non-selective NMDA receptor blocker ketamine and an NR2B-selective NMDA antagonist have been proven to provide substantial and instant clinical benefit for patients. However, both molecules, for which proof of concept has been shown before, require parenteral administration, hence an orally active therapeutic option is needed. The proof of concept Phase II study with EVT 101 was designed as a double-blind, placebo-controlled, randomized study performed with approximately 100 patients suffering from treatment-resistant depression. Treatment-resistance of patients was to be confirmed in a 6-week prospective antidepressant treatment phase preceding the actual double-blind treatment, which last 4 weeks. The main endpoints of the study were safety, tolerability, and efficacy. The antidepressant effect was assessed using MADRS and other rating scales.

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