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FibroGen Announces Promising Preliminary Data from an Open-label Phase 2 Study to Evaluate the Safety and Efficacy of FG-3019 in Individuals with Idiopathic Pulmonary Fibrosis (IPF) and Provides Program Update

FibroGen Expands Clinical Study Based on Preliminary Data Indicating Improvement in Lung Function and Lung Fibrosis in Patients with IPF

SAN FRANCISCO--(BUSINESS WIRE)--May 3, 2012 - FibroGen, Inc., today announced expansion of an ongoing 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). The company's decision to add a second, higher dose group is based on promising preliminary data from the first dose group as well as dose-escalation data from other clinical trials of FG-3019 indicating that higher doses of FG-3019 appear to be associated with a more robust biological and clinical response. FibroGen has also decided to add on another year of FG-3019 therapy for patients in the first dose group who are exhibiting stable or improved lung function in order to evaluate whether the observed maintenance of lung function continues.

IPF is a chronic, progressive, fatal lung disease for which there are no FDA-approved therapies. FG-3019 was developed to inhibit the activity of CTGF, a matricellular protein that plays a key role in fibrosis. More than a decade of research conducted by FibroGen and others has demonstrated a critical role of CTGF as a final common pathway in chronic fibrotic diseases in which persistent and excessive scarring leads to organ dysfunction and failure.

“This is the first demonstration in humans, to our knowledge, that reversal of fibrosis may be possible using a highly-targeted antifibrotic therapeutic,” said Thomas B. Neff, Chief Executive Officer of FibroGen.

A total of 54 patients having moderate to severe IPF for up to five years and aggressive disease progression have been enrolled into the first dose group in which 15 mg/kg FG-3019 is administered by intravenous infusion every 3 weeks for 45 weeks. Patients are tested every 3 months to assess changes in pulmonary function including measurement of forced vital capacity (FVC), a key indicator of both pulmonary function loss and disease-related mortality in IPF. For reference, based on placebo-treated patients in multiple recent clinical trials, patients with IPF typically experience a loss in lung function of approximately 7% predicted FVC per annum. In addition, patients are evaluated every 6 months by high resolution computed tomography (HRCT) imaging to assess structural changes in the lungs. HRCT assessments are made by pulmonary radiology experts who are using advanced digital imaging methods to quantify extent of and changes in lung fibrosis.

Combined 6-month preliminary pulmonary function and HRCT data are available for over half of the patients who remain in the study. Key preliminary findings from the first dose group include:


  • Disease severity at baseline, measured as the FVC percent predicted, ranged from 42.5% to 86.0%, with a median of 63%. These data suggest that patients enrolled in the FibroGen trial on average have greater disease severity than those enrolled in several recent IPF clinical trials with other experimental therapies.
  • A substantial proportion of the patients who entered the trial with FVC percent predicted values above the median (i.e., > 63%) are experiencing stable disease or improvement in pulmonary function, as evidenced by increasing or stable FVC measurements during the study and comparable effects on FVC percent predicted values over the same period.
  • Computer-generated HRCT data suggest that patients who entered the trial with disease severity above the median exhibit, on average, an improvement in lung fibrosis compared to baseline in two different measures of the extent of tissue scarring in the lung.
  • Improved FVC appears to correlate with decreased fibrosis.

Pharmacokinetic modeling of clinical data available on FG-3019 from this and other studies suggests that dose increases are likely to generate a more consistent response. FibroGen and its scientific and medical advisors believe that higher doses of FG-3019 as well as extended treatment of patients considered responsive may result in even better clinical outcomes.

Based on the promising preliminary results from the first dose group, as well as data from other clinical trials suggesting that higher doses of FG-3019 are associated with better responses, FibroGen is expanding the Phase 2 IPF clinical trial in two ways. First, those patients from the initial dose group who appear stable or have improving FVC levels will be given the option to continue for another year of treatment with FG-3019. In addition, another group of patients will be enrolled for treatment at a higher dose of FG-3019 (30 mg/kg every 3 weeks) to further assess the safety, tolerability, and efficacy of FG-3019 in IPF patients. FG-3019 has been well tolerated in all clinical studies to date.

“Our decisions now to extend the current study and add a higher dose group are based on the data to date from this initial dose group suggesting that FG-3019 therapy may retard or prevent predicted declines in FVC and, in some cases, may increase lung capacity as measured by FVC,” said Mr. Neff. “These are potentially very important clinical findings and are surprising in light of disease severity of patients enrolled. We are hopeful that those who may be responding to FG-3019 in the current study will continue to maintain lung capacity and show improvements with extended time on treatment, and that the new group will benefit from a higher dose.”

About FG-3019

FG-3019 has been the subject of clinical studies involving over 200 patients to date, including a Phase 1 study of patients with IPF. FibroGen is currently conducting two other clinical studies with FG-3019 in addition to the IPF study. One is a study in Hong Kong in patients with liver fibrosis as a manifestation of hepatitis B. Reversal of liver fibrosis would prevent liver failure and reduce the risk of developing hepatocellular carcinoma. The other is a study in patients with pancreatic cancer, a disease in which extensive fibrosis associated with pancreatic tumors and metastases is thought to make this aggressive form of cancer highly resistant to chemotherapy. FG-3019 has been well tolerated in all clinical studies to date with no apparent safety signals.

About CTGF and IPF

IPF is a debilitating and life-threatening lung disease characterized by a progressive scarring of the lungs that diminishes functional lung volume and hinders oxygen uptake. The cause of IPF is not known. As scarring progresses, patients with IPF experience shortness of breath (dyspnea) and difficulty with performing routine functions, such as activities of daily living. Approximately 40,000 cases of IPF are diagnosed annually in the U.S. and Canada, where the overall prevalence is estimated to be 150,000. A similar prevalence exists for six other idiopathic interstitial lung diseases and systemic sclerosis that may benefit from antifibrotic therapy. There are no FDA-approved treatments for IPF, and approximately two-thirds of patients die within five years after diagnosis. Patients are often treated with corticosteroids and immunosuppressive agents, however, no therapies have been clinically proven to improve survival or quality of life. It is thought that stabilization or reversal of lung fibrosis could stabilize lung function and diminish the impact of this devastating disease.

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.1,2 Studies have shown that CTGF causes transformation of multiple cell types into ECM-producing myofibroblasts and impairs important antifibrotic and proregenerative repair factors.3

Blockade of CTGF, in contrast, has been shown enable 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;4
  • 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 Diseases5 and in a subsequent journal article;6 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.7

CTGF is implicated as a pathogenic factor in IPF. In patients with IPF, CTGF levels are elevated in plasma,8 in transbronchial biopsy specimens, and in bronchoalveolar lavage fluid.9 Increased levels of CTGF have also been observed in experimental models of lung fibrosis.10 In addition, CTGF can cause susceptibility to experimentally-induced lung fibrosis in otherwise resistant mice.

Independent investigative teams have corroborated the reversal and regenerative effects of anti-CTGF therapy in two models of lung injury using anti-CTGF antibodies. In the first study mentioned above, FG-3019 reversed the process of fibrosis and improved lung function in a model of radiation-induced lung fibrosis.4 This model closely mimics progressive, radiation-induced lung damage in humans in which initial inflammatory stages are followed by extensive tissue remodeling and scar formation. In the second study, hyperoxia altered the development of neonatal rat lungs, inhibiting alveolarization and vascularization and promoting epithelial to mesenchymal transition and hyperplasia. Hyperoxia also induced cardiovascular remodeling leading to pulmonary hypertension, including increased pulmonary artery medial wall thickening and right ventricular hypertrophy. Treatment with FG-3149, an antibody similar to FG-3019, inhibited all of these pathologic changes, resulting in more normal lungs and hearts.11

About FibroGen, Inc.

FibroGen, Inc. was founded to discover and develop antifibrotic therapeutics. Using its expertise in the field of tissue fibrosis, in particular with matricellular proteins, such as connective tissue growth factor (CTGF), and matrix assembly enzymes, such as prolyl hydroxylases, FibroGen is now engaged in clinical development of anti-CTGF therapy and prolyl hydroxylase inhibitors for serious unmet medical needs. A placebo-controlled Phase 2 clinical trial of FG-3019 in Hong Kong addresses reversing advanced liver fibrosis and cirrhosis, the major consequences of chronic hepatitis B and C infections. Another Phase 2 pilot study addresses the ability of FG-3019 to prevent disease progression and reverse the consequences of tissue damage in idiopathic pulmonary fibrosis. Early results from an ongoing dose-escalation study in pancreatic cancer showed bioactivity of FG-3019, which is consistent with preclinical data implicating CTGF mechanistically in pancreatic cancer. From its large proprietary library of prolyl hydroxylase inhibitors, FibroGen is developing clinical and preclinical candidates designed to selectively activate HIF biology for the treatment of anemia and elicit a rapid, multifactorial, cytoprotective response for treating or preventing conditions resulting from acute ischemic injury and/or inflammation, including cardioprotection and inflammatory bowel disease. FibroGen also develops and produces recombinant human collagens and gelatins using proprietary production technology that permits making collagen essentially identical to the native protein. Development of medical devices, such as corneal implants fabricated with recombinant human collagen type III, is ongoing.

For more information about FibroGen, Inc., please visit


    1.   Mori T, et al. (1999) Role and interaction of connective tissue growth factor with transforming growth factor-beta in persistent fibrosis: A mouse fibrosis model. J Cell Physiol 181: 153-159.
    2.   Wang Q, et al. (2011) Cooperative interaction of CTGF and TGFβ in animal models of fibrotic disease. Fibrogenesis Tissue Repair 4(1):4.
    3.   Nguyen T, et al. (2008) CTGF inhibits BMP-7 signaling in diabetic nephropathy. J Am Soc Nephrol 19(11):2098-107.
    4.   Huber PE, et al. (2010) Reversal of established fibrosis by treatment with the anti-CTGF monoclonal antibody FG-3019 in a murine model of radiation-induced pulmonary fibrosis. Am J Respir Crit Care Med 181: A1054.
    5.   Lawrencia C, Brigstock DR. (2008) Targeted delivery of connective tissue growth factor siRNA to activated hepatic stellate cells resolves experimental liver fibrosis in mice. Hepatology 48:908A.
    6.   Brigstock DR (2009) Strategies for blocking the fibrogenic actions of connective tissue growth factor (CCN2): From pharmacological inhibition in vitro to targeted siRNA therapy in vivo. J Cell Commun Signal 3:5–18.
    7.   Langsetmo I, et al. (2006) Anti-CTGF human antibody FG-3019 prevents and reverses diabetes-induced cardiovascular complications in streptozotocin (STZ) treated rats. Diabetes 55(Suppl.1): A122.
    8.   Kono M, et al. (2011) Plasma CCN2 (connective tissue growth factor: CTGF) is a potential biomarker in idiopathic pulmonary fibrosis (IPF) Clinica Chimica Acta 412: 2211–2215.
    9.   Pan LH, et al. (2001) Type II alveolar epithelial cells and interstitial fibroblasts express connective tissue growth factor in IPF. Eur Respir J 17:1220-1227.
    10.   Bonniaud P, et al. (2004) CTGF is crucial to induce a profibrotic environment in “fibrosis resistant” Balb/c mouse lungs. Am J Respir Cell Mol Biol. 31(5):510-6.
    11.   Alpati S, et al. (2011) Connective Tissue Growth Factor Antibody Therapy Attenuates Hyperoxia-Induced Lung Injury in Neonatal Rats. Am J Respir Cell Mol Biol 45: 1169-1177.

Contact: FibroGen, Inc.
Contact for Patients
Loredie Lugos, 415-978-1353
Contact for Media
Laura Hansen, Ph.D., 415-978-1433


Posted: May 2012