Bitopertin


Bitopertin is a glycine reuptake inhibitor which was under development by Roche as an adjunct to antipsychotics for the treatment of persistent negative symptoms or suboptimally controlled positive symptoms associated with schizophrenia. Research into this indication has been largely halted as a result of disappointing trial results, but Roche continues to develop bitopertin for the treatment of obsessive–compulsive disorder.
Bitopertin is a glycine transporter 1 inhibitor that increases levels of the neurotransmitter glycine by inhibiting its reuptake from the synaptic cleft. Glycine acts as a required co-agonist along with glutamate at N-methyl-D-aspartate receptors. Dysfunction of NMDA receptors may play a key role in the pathogenesis of schizophrenia and modulation of glutamatergic signalling via increased concentrations of glycine in the synaptic cleft may help potentiate NMDA receptor function and improve the symptoms of schizophrenia.
In a phase II proof-of-concept study, patients on bitopertin experienced a significant improvement in the change of the Negative Symptom Factor Score from baseline within 8 weeks. In addition, 83% of patients on bitopertin described an improvement of negative symptoms on the CGI-I1 versus 66% on placebo.
In January 2014, Roche reported that bitopertin failed to meet its endpoints in two phase III trials assessing its efficacy in reducing negative symptoms of schizophrenia. Subsequently, in April 2014, Roche announced that it was discontinuing all except one of its phase III trials of bitopertin for schizophrenia.
Though Roche has largely ceased its studies of bitopertin for schizophrenia, it is also investigating the drug in the treatment of OCD, and is continuing its development for this indication. As of August 2014, bitopertin is in phase II clinical trials for OCD.