FibroGen On Track for Duchenne Treatment Clinical Trial

A researched-based biopharma called Fibrogyn announced last month that the FDA had completed their review of their new drug application, FG-3019. The drug is aimed to work with patients with Duchenne Muscular Dystrophy. A clinical study may now proceed. Non-ambulatory patients (those no longer able t walk) may be viable candidates for this Phase 2 trial later this year.

FG-3019 is a fully human monoclonal antibody that inhibits the activity of connective tissue growth factor (CTGF), a common mediator of fibrotic disease. FG-3019 is currently in Phase 2 clinical studies for idiopathic pulmonary fibrosis and pancreatic cancer.

This submission is the culmination of nearly 10 years of research by FibroGen and its collaborators to understand the role of CTGF in DMD. Data from these investigations, including the testing of FG-3019 in preclinical models of DMD, have appeared in several peer reviewed publications.(1) FibroGen has met with panels of international muscular dystrophy experts, including the TREAT-NMD Advisory Committee for Therapeutics, to review these findings, discuss the rationale for FG-3019 as a potential treatment for DMD, and refine the clinical trial design.(2) There has been consistent support in these panels for the advancement of FG-3019 development in DMD.

In DMD, muscle cells are damaged due to the absence of the dystrophin protein complex necessary for normal muscle fiber function. Absence of dystrophin leads to muscle damage, inflammation, fibrosis, and progressive dysfunction and weakness in the muscles of DMD patients. The extent of diminished muscle function directly correlates with the extent of intra-muscular fibrosis. The rationale for FG-3019 in DMD is based on data that show CTGF reduces the ability of damaged muscle cells to repair themselves and promotes muscle fibrosis. In preclinical studies, FG-3019 reduced muscle fibrosis and significantly improved muscle function. Separately, in clinical trials of another fibrotic condition, idiopathic pulmonary fibrosis, FG-3019 was shown to reverse fibrosis in a significant proportion of patients.

“We believe FG-3019 may have the ability to not only stabilize but also reverse the progression of fibrosis in disease,” stated Frank H. Valone, MD, Chief Medical Officer of FibroGen. “If FG-3019 shows a positive effect on fibrosis in clinical studies of DMD patients, and inhibits or reverses the build-up of fibrosis in their skeletal muscle, FG-3019 could become a potential therapy for the muscle weakness and wasting associated with the disease. Whereas other investigational treatments focus on overcoming certain genetic mutations present in a subpopulation of DMD patients, FG-3019 addresses the disease process of muscle displacement by fibrosis seen in a broader population of DMD patients. We plan to initiate our first DMD trial at US sites and begin enrolling non-ambulatory subjects this year.”

About FG-3019

FG-3019 is an investigational therapeutic antibody developed by FibroGen to inhibit the activity of connective tissue growth factor (CTGF), a common factor in chronic fibrotic and proliferative disorders characterized by persistent and excessive scarring that can lead to organ dysfunction and failure. FibroGen is currently conducting clinical studies of FG-3019 in idiopathic pulmonary fibrosis and pancreatic cancer. FG-3019 has been well tolerated, with no apparent safety signals, in nine Phase 1 and Phase 2 clinical studies and more than 350 treated patients to date.

About Duchenne Muscular Dystrophy

According to Parent Project Muscular Dystrophy, Duchenne muscular dystrophy is the most common fatal genetic disorder diagnosed in childhood, affecting approximately 1 in every 3,500 newborn boys. Because the Duchenne gene is found on the X-chromosome, it primarily affects males. Duchenne patients begin to show signs of muscle weakness as early as the age of 2. The disease gradually weakens the skeletal or voluntary muscles in the arms, legs and trunk, and Duchenne patients are often wheelchair bound before the age of 12. The progressive muscle weakness leads to serious medical problems, particularly issues relating to the heart and lungs. Young men with Duchenne typically live into their late twenties.