Investors and Media

SAN FRANCISCO, Jan. 06, 2016 (GLOBE NEWSWIRE) -- FibroGen, Inc. (NASDAQ:FGEN) (“FibroGen”) announced today 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.¹
• 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.²
• Elevated levels of CTGF are seen in the muscle of DMD patients.³

The Phase 2 clinical study of non-ambulatory DMD patients evaluates the therapeutic potential of FG-3019 in three areas:

1. 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.
2. 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.
3. 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.

“While the fibrotic component of DMD pathology is well recognized, treatment options for attacking this aspect of the disease have been limited,” said Thomas Voit, MD, Director Designate, Biomedical Research Centre, Institute of Child Health, Great Ormond Street Hospital Trust, London, UK. “This study of FG-3019, a novel anti-fibrotic monoclonal antibody, has the potential to establish fibrosis mitigation as a foundational component of comprehensive DMD therapy.”

“FG-3019, if shown to be safe and effective, has the potential to be a disease modifying therapy for DMD,” said Thomas Neff, chief executive officer of FibroGen. “By countering the activity of elevated CTGF and its harmful effects on muscle tissue, FG-3019 may be able to help DMD patients regardless of genetic subtype. We look forward to working closely with clinical trial investigators, study coordinators, and the DMD community as we advance the clinical development of FG-3019 in this devastating disease.”

Study Design

The open-label, single-arm Phase 2 study will evaluate the safety and efficacy of FG-3019 in up to 22 non-ambulatory DMD patients who are at least 12 years of age. Each patient will receive FG-3019 (35 mg/kg, every two weeks) for up to two years. All patients will receive full supportive care as required by their clinical condition and will be closely monitored for safety. Efficacy endpoints include changes in pulmonary function, upper body muscle strength, cardiac fibrosis, and other measures. Efficacy assessments will be performed routinely over the course of the study, including pulmonary and muscle function tests approximately every four months and MRIs once a year. An interim analysis of safety and efficacy will be performed after all evaluable subjects complete one year of dosing. If the interim analysis indicates a potential benefit from FG-3019, the study will be extended to two years. Additional information is available on ClinicalTrials.gov. https://clinicaltrials.gov/show/NCT02606136

About Duchenne Muscular Dystrophy

Duchenne muscular dystrophy is a rare and debilitating neuromuscular disease that affects approximately 1 in every 3,500 newborn boys. The fatal disease is caused by a genetic mutation leading to the absence or defect of dystrophin, a protein necessary for normal muscle function. The absence of dystrophin results in muscle weakness, muscle loss, fibrosis, and inflammation. Patients with DMD are often wheelchair-bound before the age of 12, and their progressive muscle weakness may lead to serious medical problems relating to respiratory and cardiac muscle.

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, pancreatic cancer and Duchenne muscular dystrophy. FG-3019 has been well tolerated, with no apparent safety signals, in ten Phase 1 and Phase 2 clinical studies and more than 350 treated patients to date. The safety and efficacy of FG-3019 have not been established.

1. Morales et al. Journal of Pathology 2011, Vol. 225: 490–501
2. Vial et al. Journal of Cell Physiology 2008, Vol. 215: 410–421
3. Sun et al. Journal of the Neurological Sciences 2008, Vol. 267,  48–56

About FibroGen

This release contains forward-looking statements, including statements regarding the potential for continued safety and potential of FG-3019 to become a therapy and our expectations regarding the initiation and conduct of, and potential results from a clinical trial of FG-3019 for the treatment of DMD in non-ambulatory patients. Our actual results may differ materially from those indicated in these forward-looking statements due to risks and uncertainties that are described in our Annual Report on Form 10-K and our quarterly reports on Form 10-Q filed with the Securities and Exchange Commission, including the risk factors set forth therein. Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release and we undertake no obligation to update any forward-looking statement in this press release, except as required by law.

Contact:

Leanne C. PriceFibroGen, Inc.lprice@fibrogen.com
415.978.1740