Date: 2016-03-11
Type of information: Publication of results in a medical journal
phase: 2
Announcement: publication of results the European Respiratory Journal
Company: FibroGen (USA - CA)
Product: pamrevlumab (FG-3019)
Action
mechanism: monoclonal antibody. 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. While the safety and efficacy of FG-3019 have not been established, it has been well tolerated to date, with no apparent safety signals in ten Phase 1 and Phase 2 clinical studies and more than 350 treated patients to date. In desmoplastic, or fibrotic, cancers such as pancreatic cancer, CTGF in the extensive fibrous stroma associated with the tumor promotes abnormal proliferation of stromal cells and tumor cells, induces extracellular-matrix, or ECM, deposition that provides a substrate for tumor cell adherence, promotes angiogenesis, and promotes metastasis by enhancing cell motility, invasion, and survival. Studies in a transgenic mouse model of pancreatic cancer indicate that treatment with FG-3019 in combination with chemotherapy may enhance the efficacy of chemotherapy and improve survival.
Disease: idiopathic pulmonary fibrosis
Therapeutic area: Lung diseases - Respiratory diseases - Rare diseases
Country: USA
Trial
details: This phase 2 trial is evaluating the safety and tolerability of FG-3019 in subjects with Idiopathic Pulmonary Fibrosis (IPF) and the efficacy of FG-3019 for attenuating fibrosis in these subjects. (NCT01262001)
Latest
news: * On March 11, 2016, FibroGen announced that the European Respiratory Journal 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 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 idiopathic pulmonary fibrosis severity to assess safety and efficacy of FG-3019. While other recent clinical trials in idiopathic pulmonary fibrosis 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 idiopathic pulmonary fibrosis . 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 idiopathic pulmonary fibrosis000 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 idiopathic pulmonary fibrosis patients. The two doses of FG-3019 administered to idiopathic pulmonary fibrosis 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 data, FibroGen is conducting a randomized placebo controlled Phase 2 trial in idiopathic pulmonary fibrosis, 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.
