Benzinga | Dec 22, 2020 07:03AM EST

FibroGen Advances Phase 3 Clinical Development of Pamrevlumab for the Treatment of Idiopathic Pulmonary Fibrosis with Initiation of ZEPHYRUS-2

FibroGen, Inc. (NASDAQ:FGEN) today announced dosing of the first patient in the ZEPHYRUS-2 Phase 3 clinical study of pamrevlumab in patients with idiopathic pulmonary fibrosis (IPF), a chronic, progressive, and fatal lung disease.

"Today, treatment for IPF is aimed at relieving symptoms and slowing disease progression, and disease-modifying treatment options are urgently needed," said Elias Kouchakji, M.D., Senior Vice President, Clinical Development and Drug Safety. "We are excited to advance the Phase 3 clinical development program for pamrevlumab, a first-in-class antibody which represents a novel approach to the treatment of IPF, a disease with survival rates comparable to those of some of the deadliest cancers."

ZEPHYRUS-2 is a 52-week randomized, double-blind, placebo-controlled, multi-center Phase 3 trial designed to evaluate the efficacy and safety of pamrevlumab in subjects with IPF who were previously treated with an approved therapy but who discontinued that therapy.

The primary endpoint of the study is disease progression defined as a change from baseline in forced vital capacity (FVC) percent predicted decline ?10% or death. Secondary endpoints include change in quantitative lung fibrosis (QLF) and patient-reported outcomes. Approximately 340 subjects will be enrolled into the global study. Subjects who complete the 52-week study may be eligible for rollover into a separate study offering open-label, extension treatment with pamrevlumab. For more information about ZEPHYRUS-2 please visit www.clinicaltrials.gov (NCT04419558).

"The initiation of our second Phase 3 study of pamrevlumab for IPF furthers our research on the clinical benefits of inhibiting connective tissue growth factor (CTGF), an important biological mediator in fibrotic and proliferative disorders," said Mark Eisner, M.D, M.P.H, Chief Medical Officer, FibroGen. "We are committed to advancing the science of CTGF biology and evaluating clinical benefit in diverse diseases with unmet medical need, including IPF, locally advanced unresectable pancreatic cancer and Duchenne muscular dystrophy."

The Phase 3 clinical development program for pamrevlumab for IPF consists of two studies, ZEPHYRUS and ZEPHYRUS-2. ZEPHYRUS is an ongoing randomized, double-blind, placebo-controlled, multi-center Phase 3 trial designed to evaluate the efficacy and safety of pamrevlumab in subjects with IPF over a 52-week period. The primary endpoint of the study is the change in forced vital capacity (FVC) from baseline. For more information about ZEPHYRUS please visit www.clinicaltrials.gov (NCT03955146).

The design of ZEPHYRUS and ZEPHYRUS-2 is supported by safety and efficacy data from two Phase 2 studies. In a Phase 2, randomized, double-blind, placebo-controlled trial of pamrevlumab in IPF (Study 067/PRAISE), pamrevlumab demonstrated a statistically significant difference over placebo in the primary efficacy endpoint of FVC percent predicted change from baseline to Week 48 (Gorina, ERS 2017). Pamrevlumab achieved superiority over placebo in the following secondary endpoints: the proportion of subjects with disease progression (defined as a change from baseline in FVC percent predicted decline ?10% or death), time to disease progression, change from baseline to Week 48 in quantitative lung fibrosis (QLF) score to Week 48 measured by quantitative HRCT. In addition, there was a trend towards improvement in patient-reported quality of life measurements assessed by the SGRQ (positive trends) and the UCSD-SOBQ, as well as favorable trend in all-cause mortality.

In a prior single-arm, open-label FGCL-3019-049 study, the treatment of patients with IPF given 15 mg/kg and 30 mg/kg IV of pamrevlumab every three weeks was associated with improvement or stability in quantified scores of whole lung fibrosis in approximately 35% of subjects at Week 48 (Raghu, 2012). Changes from baseline in these scores were significantly correlated with changes in FVC percent predicted value (Raghu, 2012).