Basimglurant (DB11833): A Comprehensive Pharmacological and Clinical Development Report on a Repurposed mGluR5 Modulator

Executive Summary

Basimglurant is an investigational, orally bioavailable, small molecule drug that functions as a potent and selective negative allosteric modulator (NAM) of the metabotropic glutamate receptor 5 (mGluR5).[1] Its development history provides a compelling case study in modern pharmaceutical strategy, characterized by initial setbacks in broad indications followed by a strategic pivot to targeted rare diseases.

Originally developed by Roche and Chugai Pharmaceutical under the developmental codes RG-7090 and RO-4917523, Basimglurant was first evaluated for the treatment of Major Depressive Disorder (MDD) and Fragile X Syndrome (FXS).[4] This initial strategy was predicated on the prevailing hypotheses implicating glutamatergic system dysfunction in the pathophysiology of these conditions. Despite demonstrating a favorable pharmacokinetic profile suitable for once-daily dosing and being generally well-tolerated in early clinical studies, Basimglurant ultimately failed to meet its primary efficacy endpoints in pivotal Phase II clinical trials for both MDD and FXS.[5] The combination of insufficient efficacy and the emergence of concerning psychiatric adverse events in the FXS trial led Roche to discontinue its development programs for these indications.