Bitopertin

Bitopertin (GLYT-1; RO-4917838; RG1678) is a drug under development intended to be used in combination with antipsychotics for the treatment of persistent negative symptoms or sub-optimally controlled positive symptoms associated with schizophrenia. If licensed, bitopertin would represent the first in a new class of treatments for this patient group.

Bitopertin is a glycine transporter type 1 (GlyT1) 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. Bitopertin is administered orally at 10 mg or 20 mg once daily for 56 weeks.

Roche is co-developing RG1678 globally with Chugai.

In a Phase II proof-of-concept study patients on RG1678 experienced a significant improvement in the change of the Negative Symptom Factor Score from baseline within 8 weeks (from −4.86 in the placebo group to −6.65 in the treatment group, p<0.05, per-protocol population). In addition, 83% of patients on RG1678 described an improvement of negative symptoms on the CGI-I1 vs 66% on placebo (p<0.05, per-protocol population).

Phase III trials are currently underway and expected to be completed by 2015.