Development and Optimization of the Manufacturing Process for RNA-Splicing Modifier Risdiplam RG7916

We outline the discovery and the process development for risdiplam, a potent oral splicing modifier approved as Evrysdi® for the treatment of spinal muscular atrophy. The evolution of the manufacturing process is described from the discovery route to the commercial process for this highly accelerated project that was commercialized only 4.5 years after the start of clinical trials. We present the various synthetic approaches that have been pursued to support different stages of the preclinical and clinical development and discuss the issues that led to the development of the final commercial process.