FibroGen initiates FG-3019 open-label phase 2 study in idiopathic pulmonary fibrosis

FibroGen, Inc. today announced initiation of an open-label phase 2 study to evaluate the safety, tolerability, and efficacy of FG-3019, a human monoclonal antibody against connective tissue growth factor (CTGF), in individuals with idiopathic pulmonary fibrosis (IPF), a chronic, progressive, fatal lung disease for which there are no FDA-approved therapies.

“Based on evidence from nonclinical studies that FG-3019 can reverse the process of lung fibrosis, we are hopeful that FG-3019 will prove clinically beneficial in patients with IPF.”

The development of IPF is not completely understood but is thought to result from repetitive injury to epithelial cells that line the lungs. This initiates an abnormal wound healing process characterized by activation of cells called myofibroblasts, which produce and deposit excessive amounts of extracellular matrix (ECM). ECM deposition and tissue remodeling are key elements in the process of fibrosis that can eventually severely damage the lungs.

While different traumas and multiple biological factors can initiate the fibrotic process, CTGF is the final common element essential for chronic fibrosis. Studies have shown that CTGF causes transformation of multiple cell types into ECM-producing myofibroblasts and impairs important anti-fibrotic and pro-regenerative repair factors.

Blockade of CTGF, in contrast, has been shown to favor a state of regenerative tissue repair:

• administration of FG-3019 was reported to reverse fibrotic processes in a model of radiation-induced lung fibrosis at the 2010 annual meeting of the American Thoracic Society (also see below "About CTGF and Idiopathic Pulmonary Fibrosis");

• preventative and curative effects resulting from genetic blockade of CTGF using siRNA were reported in a model of liver fibrosis at the 2008 annual meeting of the American Association for the Study of Liver Diseases and in a subsequent journal article; and

• reversal of vascular remodeling using FG-3019 in a model of type 1 diabetes mellitus was reported at the 2006 annual meeting of the American Diabetes Association.

"What sets our program apart is that FG-3019 targets the central mediator of fibrosis whereas other approaches target modification of indirect fibrogenic factors or a single point in the process," said Thomas B. Neff, Chief Executive Officer of FibroGen. "CTGF is at the center of multiple positive feedback loops that, irrespective of etiology, drive the fibrosis process. We believe anti-CTGF is the only currently known therapeutic approach having potential to alter disease progression."

The phase 2 study is expected to enroll 48 patients with progressive IPF, who will receive intravenous infusions of FG-3019 every 3 weeks for 45 weeks. Safety, tolerability, and the effect of FG-3019 on extent of lung fibrosis (as measured by CT scan), lung function, and shortness of breath will be assessed.

"This is an important study that will examine the ability of anti-CTGF therapy to attenuate fibrosis and improve lung function in patients with IPF," said Frank Valone, MD, Chief Medical Officer of FibroGen. "Based on evidence from nonclinical studies that FG-3019 can reverse the process of lung fibrosis, we are hopeful that FG-3019 will prove clinically beneficial in patients with IPF."