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FibroGen Receives FDA Clearance to Proceed With Clinical Study of FG-3019 in Duchenne Muscular Dystrophy

SAN FRANCISCO, July 27, 2015 (GLOBE NEWSWIRE) -- FibroGen, Inc. (Nasdaq:FGEN), a research-based biopharmaceutical company, today announced that the U.S. Food and Drug Administration (FDA) has completed its review of the Company's investigational new drug (IND) application for the study of FG-3019 in patients with Duchenne muscular dystrophy (DMD), and clinical study may proceed. 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.

The IND enables FibroGen to initiate a multi-site Phase 2 trial exploring FG-3019 for the treatment of DMD in non-ambulatory patients, scheduled to begin later this year. 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.

Notes

(1) Au et al. (2011) Increased connective tissue growth factor associated with cardiac fibrosis in the mdx mouse model of dystrophic cardiomyopathy, International Journal of Experimental Pathology 92: 57-65; Desguerre et al. (2009) Endomysial fibrosis in Duchenne muscular dystrophy: A marker of poor outcome associated with macrophage alternative activation, Journal of Neuropathology and Experimental Neurology 68: 762-773; Morales et al. (2011) CTGF/CCN-2 over-expression can directly induce features of skeletal muscle dystrophy, Journal of Pathology 225: 490–501; Morales et al. (2013) Reducing CTGF/CCN2 slows down mdx muscle dystrophy and improves cell therapy, Human Molecular Genetics, 1-14; Pessina et al. (2014) Novel and optimized strategies for inducing fibrosis in vivo: focus on Duchenne Muscular Dystrophy, Skeletal Muscle 4: 7-24; Sun et al. (2008) Connective tissue growth factor is overexpressed in muscles of human muscular dystrophy, Journal of Neurological Sciences 267: 48-56; Vial et al. (2008) Skeletal muscle cells express the profibrotic cytokine connective tissue growth factor (CTGF/CCN2), which induces their dedifferentiation, Journal of Cellular Physiology 215: 410-421.

(2) http://www.treat-nmd.eu/resources/tact/reviews/past/fg-3019/.

About FibroGen

FibroGen is a research-based biopharmaceutical company focused on the discovery, development and commercialization of novel therapeutics to treat serious unmet medical needs. The company utilizes its extensive experience in fibrosis and hypoxia-inducible factor (HIF) biology to generate development programs in multiple therapeutic areas. Its most advanced product candidate, roxadustat, or FG-4592, is an oral small molecule inhibitor of HIF prolyl hydroxylases, or HIF-PHs, in Phase 3 clinical development for the treatment of anemia in CKD. A second product candidate, FG-3019, is a monoclonal antibody in Phase 2 clinical development for the treatment of idiopathic pulmonary fibrosis (IPF), pancreatic cancer and liver fibrosis.

Forward Looking Statements

This release contains forward-looking statements, including statements regarding the potential for continued safety and potential to become a therapy of FG-3019 and our expectations regarding the initiation 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: FibroGen, Inc. Greg Mann 415-978-1433 gmann@fibrogen.com

Source:FibroGen, Inc.