SAN FRANCISCO, March 11, 2016 (GLOBE NEWSWIRE) -- FibroGen, Inc. (NASDAQ:FGEN) (FibroGen) announced today that the European Respiratory Journal (“ERJ”) published on-line a manuscript entitled, “FG-3019 anti-connective tissue growth factor monoclonal antibody: results of an open-label clinical trial in IPF,” from a Phase 2 clinical study in subjects with idiopathic pulmonary fibrosis (IPF) treated for 48 weeks with the investigational drug FG-3019, a monoclonal antibody that inhibits the activity of connective tissue growth factor (CTGF), a central mediator of fibrotic disease. In the study, lung fibrosis, as measured by quantitative high resolution computed tomography (HRCT), was shown to be reduced in a portion of subjects who received FG-3019. Subjects with reduced or stable fibrosis showed lung function results that were better overall than those for whom fibrosis continued to increase.
The exploratory study enrolled patients with a wide range of IPF severity to assess safety and efficacy of FG-3019. While other recent clinical trials in IPF have assessed efficacy in terms of changes in pulmonary function, this Phase 2 open-label study measured efficacy by changes in both pulmonary function, measured by forced vital capacity (FVC), and pulmonary fibrosis, assessed using quantitative high resolution computed tomography (HRCT), the tool employed to confirm diagnosis of IPF. Subjects in two cohorts received intravenous doses of FG-3019 of either 15 mg/kg or 30 mg/kg every three weeks for 45 weeks. The publication provides an analysis of safety and efficacy data from all subjects treated in the study. Of the 89 subjects who received one or more doses, 75 subjects completed 24 weeks and 66 of these subjects completed 48 weeks of treatment and assessment of changes in pulmonary structure and function.
Based on results obtained in pre-clinical studies in radiation-induced pulmonary fibrosis, FibroGen’s hypothesis was that FG-3019 treatment could reverse lung fibrosis. Extent of and changes in lung fibrosis were assessed using quantitative time series of HRCT imaging at baseline, week 24, and week 48. Quantitative HRCT is a computer-based imaging method to measure fibrotic profile and changes in fibrosis affecting lung tissue over time. Other peer-reviewed publications based on similar quantitative HRCT methods have identified an association between fibrosis worsening and mortality in IPF.1, 2 While the majority of subjects in the study (65%) exhibited an increase in fibrosis, 35% exhibited stable or improved fibrosis at week 48 as measured by HRCT. Furthermore, at both 24 and 48 week time points, improvements in lung fibrosis correlated with improvements in lung function. We believe that this is the first clinical trial to indicate improvement in fibrosis in IPF patients.
The two doses of FG-3019 administered to IPF patients by intravenous infusion every 3 weeks for 45 weeks were well tolerated in the patients enrolled in this study. Adverse events were generally mild. Twenty-four of 89 treated subjects (27.0%) experienced a total of 38 treatment-emergent serious adverse events (SAEs) during the trial. The type and frequency of SAEs were consistent with those expected in the study population. Subjects with a wide range of disease severity were enrolled in the trial. In the initial cohort, inclusion criteria were FVC values from 45% to 90% predicted. After the results across that population were studied, the FVC inclusion range was shifted to FVC values of 55% predicted or greater in the second cohort. The study was designed to be open-label and thus did not include a placebo control group. FG-3019-treated subjects in this study showed an average FVC decline from baseline of 140 mL over the treatment period of 48 weeks. Of the subjects who completed a 48-week course of treatment, 13.6% experienced FVC % predicted decline from baseline of ≥10%, while 30% of treated subjects showed an increase from baseline of FVC % predicted (range 0.2–14.1%).
Based on these encouraging data, FibroGen is conducting a randomized placebo controlled Phase 2 trial in IPF, currently enrolling in the US and other countries. A sub-study has recently been added to the trial to evaluate the combination of FG-3019 with drugs recently approved by FDA for IPF treatment.
In an accompanying editorial, Dr. Luca Richeldi, Professor of Respiratory Medicine and Chair of Interstitial Lung Disease at University of Southampton, stated: “The fact that, to the best of current knowledge, neither of the two currently approved IPF treatments are targeting CTGF poses a promising basis for a future placebo-controlled trial combining FG-3019 with either pirfenidone and/or nintedanib.”
“To our knowledge, this is the first report of improved pulmonary fibrosis in IPF patients reported in a peer-reviewed journal” said FibroGen Chief Executive Officer, Thomas B. Neff. “We believe this exploratory study provides an indication of the therapeutic potential for FG-3019 in interstitial lung disease and other conditions characterized by the fibrotic process. Many of the subjects in this study responding to FG-3019 have continued on an open label extension for up to 4 years and 9 months. We continue to follow that subset and will seek to report results at an appropriate juncture.”
References
1) Maldonado F, Moua T, Rajagopalan S, et al. Automated quantification of radiological patterns predicts survival in idiopathic pulmonary fibrosis. Eur Respir J 2014; 43: 204-212.
2) Oda K, Ishimoto H, Yatera K, et al. High-resolution CT scoring system-based grading scale predicts the clinical outcomes in patients with idiopathic pulmonary fibrosis. Respir Res 2014; 15: 10.
About Idiopathic Pulmonary Fibrosis (IPF)
IPF is a 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, and approximately two-thirds of IPF patients die within five years after diagnosis.
About FG-3019
FG-3019 is an investigational therapeutic monoclonal 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 eleven clinical studies and more than 470 treated patients to date.
About FibroGen, Inc.
FibroGen is a research-based biopharmaceutical company focused on the discovery, development and commercialization of novel therapeutics to treat serious unmet medical needs. We have capitalized on our extensive experience in fibrosis and hypoxia-inducible factor (HIF) biology to generate multiple programs targeting various therapeutic areas. Our most advanced product candidate, roxadustat, or FG-4592, is an oral small molecule HIF prolyl hydroxylase (HIF-PH) inhibitor, in Phase 3 clinical development for the treatment of anemia in chronic kidney disease (CKD). Our 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 Duchenne muscular dystrophy. For more information about FibroGen, please visit www.fibrogen.com.
Forward Looking Statements
This release contains forward-looking statements, including statements regarding the potential benefit of FG-3019 for patients with IPF, including the potential for reversal of pulmonary fibrosis. Our actual results may differ materially from these early data and any forward-looking statements due to risks and uncertainties that are described in our filings 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.