FibroGen recently announced the publication of results from a Phase 2 clinical trial (NCT01262001) in patients with idiopathic pulmonary fibrosis (IPF), testing a 48-week treatment with the company’s investigational drug FG-3019, a monoclonal antibody that inhibits the activity of the critical mediator of fibrotic disease: the connective tissue growth factor (CTGF).
The study, “FG-3019 anti-connective tissue growth factor monoclonal antibody: results of an open-label clinical trial in IPF,” was published in the European Respiratory Journal.
The exploratory Phase 2 open-label clinical trial enrolled patients with different severity levels of IPF, with the goal to investigate the effectiveness and safety of FG-3019. Trial endpoints included changes in pulmonary function measured by forced vital capacity (FVC), and changes in pulmonary fibrosis assessed through quantitative high-resolution computed tomography (HRCT).
Patients were treated every three weeks for 45 weeks with FG-3019 at doses of 15 mg/kg or 30 mg/kg. Based on data from pre-clinical trials in radiation-induced pulmonary fibrosis, FibroGen’s proposition was that treatment with FG-3019 would be able to reverse lung fibrosis. The trial endpoints were assessed with quantitative time series of HRCT imaging at baseline, and after 24 and 48 weeks of treatment.
The results showed that although more patients (65 percent) had an increase in fibrosis, 35 percent had stable or improved fibrosis following 48 weeks of treatment with FG-3019. The results also showed that at week 24 and week 48, lung fibrosis improvements were positively correlated with lung function improvements.
Patients treated with FG-3019 showed an average FVC decline from baseline of 140 mL over the 48-week treatment period. Of the patients who completed the 48 weeks of treatment, 13.6 percent had a decline of FVC percent predicted from baseline of greater or equal to 10 percent, while 30 percent had an increase from baseline of FVC percent predicted (range 0.2 to 14.1 percent).
In terms of safety profile, the drug was found to be well-tolerated by the participants. In total, 24 of the 89 patients treated with FG-3019 (27.0 percent) had 38 treatment-emergent serious adverse events (SAEs), although generally mild.
Based on the positive results, FibroGen is currently enrolling IPF patients in the U.S. and in other countries for a randomized, placebo-controlled Phase 2 clinical trial (NCT01890265). A sub-trial was added to the main trial to assess FG-3019 in combination with FDA-approved drugs for IPF .
“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,” wrote Dr. Luca Richeldi, professor of respiratory medicine and chair of interstitial lung disease at University of Southampton, in an accompanying editorial, according to a press release.
“To our knowledge, this is the first report of improved pulmonary fibrosis in IPF patients reported in a peer-reviewed journal,” said FibroGen CEO 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 four years and nine months. We continue to follow that subset and will seek to report results at an appropriate juncture,” Neff said.