Clinical Trial of FG-3019 in patients with Duchenne muscular dystrophy (DMD)

Seth Porter, PhD

25th October 2014

FibroGen (http://www.fibrogen.com/) has developed FG-3019, a human monoclonal IgG1 Kappa antibody directed against CTGF (connective tissue growth factor). FG-3019 is being developed as an anti-fibrotic agent. To date, FG-3019 has been administered to more than 300 human subjects in clinical trials conducted by FibroGen, including trials for adults with idiopathic pulmonary fibrosis (IPF) and pancreatic cancer, with promising preliminary results. Results in IPF suggest that FG-3019 reverses fibrosis in a subset of human subjects.  The rationale for using FG-3019 in DMD is based on observations that CTGF levels are increased in DMD and that fibrosis is a major contributor to muscle dysfunction in DMD.  Morales et al. (Hum Mol Gen 2013) examined mdx mice with a genetic reduction in CTGF and found reduced disease progression, with results demonstrating a reduction in creatine kinase (CK), fibrosis, embryonic myosin, and myogenin. A small cohort of mdx mice, treated with FG-3019 for two months, showed increased myofibril size, reduction in fibrosis and serum CK, and improved strength in the gastrocnemius muscle. Based on this published data and on newer mdx mouse data,  FibroGen proposed a clinical trial in boys with DMD. Overall, TACT felt that there was compelling evidence from a variety of approaches − including genetic, pharmacologic, and immunological − to support the use of anti-fibrotic agents in DMD and to support the potential use of FG-3019 as one of these agents. The committee also felt there were a number of aspects in the proposed clinical trial design that would benefit from greater input from experts in DMD clinical trials, and recommended that FibroGen enlist the consultation of clinical advisors with experience in DMD clinical research or design.

12 Apr 2017