FibroGen, Inc. announced enrollment of the first two patients in an open-label, multicenter Phase 2 clinical trial of the investigational compound FG-3019 in patients with Duchenne muscular dystrophy (DMD). DMD, a disease characterized by progressive muscle degeneration and weakness, is caused by genetic mutations that result in the absence of normally functioning dystrophin protein. The absence of dystrophin leads to muscle damage involving, among other processes, the replacement of muscle with fibrotic and fat tissue.

FG-3019 is a fully human monoclonal antibody against connective tissue growth factor (CTGF), a central mediator of fibrosis. FG-3019 was studied in an open-label Phase 2 clinical study in 89 patients with idiopathic pulmonary fibrosis (IPF) and is being further evaluated in a randomized placebo-controlled Phase 2 study in IPF. Results from the open-label study have supported further investigation of the potential of FG-3019 to treat fibrotic disease.

Research on the relationship of DMD and CTGF conducted by FibroGen and others has shown that: CTGF over-expression in muscle of normal mice caused extensive skeletal muscle damage, fibrosis, and decreased muscle strength; CTGF inhibits muscle cell differentiation, the normal biological process in which muscle cells are formed, and causes de-differentiation, or the breakdown, of mature muscle cells; Elevated levels of CTGF are seen in the muscle of DMD patients. The Phase 2 clinical study of non-ambulatory DMD patients evaluates the therapeutic potential of FG-3019 in three areas: The potential to slow the loss of, stabilize, or regain diaphragm and intercostal muscle strength and thereby preserve or improve pulmonary function in non-ambulatory DMD patients. By the time DMD patients lose ambulation, their pulmonary function has steadily declined to a point where many require pulmonary assistance.

Pulmonary function will be the primary efficacy assessment of the trial. The potential to slow the loss of, stabilize, or regain upper body muscle strength and thereby preserve the ability of DMD patients to use their arms for normal daily functions. As the disease progresses, patients' ability to use arms and hands declines steadily.

Forearm muscle fibrosis will be measured by MRI in the trial as well as by functional assays of strength and mobility. The potential to slow, stabilize, or reverse cardiomyopathy. As in skeletal muscle, fibrosis progresses steadily in the heart muscles of DMD patients.

Cardiomyopathy is the cause of death for many DMD patients. Cardiac fibrosis and function will be evaluated by MRI in the study.