Partnering to treat an Orphan Disease Duchenne Muscular Dystrophy

Principal Investigator: Kathryn Wagner

The goal of this program is to develop an investigational drug by Sanofi for a new indication, Duchenne Muscular Dystrophy.  The program includes preclinical toxicology and efficacy studies as well as Phase 1 and Phase 2a studies in DMD. We propose to repurpose a Sanofi drug which is an oral, soluble guanylate cyclase (sGC) activator with an excellent safety and tolerability profile. It has been shown that modulation of the NO-cGMP pathway improves cardiac and skeletal muscle function in the mdx mouse model of DMD. The study now propose to determine if this Sanofi drug, which acts downstream of PDE inhibitors, provides benefit to DMD. The pre-clinical study will test efficacy of the drug in the mdx/utr mouse model of DMD and juvenile toxicology studies will be performed. Following IND filing with the FDA, a Phase Ib SAD/ MAD/extension study will be performed in 3 sites for safety and dose finding in a limited number of DMD subjects.  Following this, a Phase IIb study in 5 clinical sites will determine if the drug will result in functional improvement in DMD as well as whether its sustained administration is safe and well tolerated in DMD. Given the life-threatening and disabling nature of DMD the Phase IIb is anticipated to be the pivotal clinical trial for seeking provisional FDA approval.