Pamrevlumab (FG-3019) is an experimental therapy being developed by FibroGen to treat pulmonary fibrosis.

Pamrevlumab has been granted fast track designation by the U.S. Food and Drug Administration (FDA) for its potential as a treatment.

How pamrevlumab works

Pulmonary fibrosis is characterized by the formation of scar tissue in the lungs, interfering with lung function and leading to symptoms like difficulty breathing, shortness of breath, and coughing. The majority of pulmonary fibrosis cases are idiopathic, meaning that the cause of scar tissue formation (fibrosis) is not known, although risk factors such as smoking have been identified. Whatever the primary cause, the immune system acts on the lungs to increase inflammation, leading to cell death and fibrosis.

Pamrevlumab is a human antibody that recognizes and binds to a protein called connective tissue growth factor, or CTGF. CTGF is involved in the progression of tissue fibrosis — it recognizes several inflammatory cytokines (signaling molecules that transmit inflammation signals from one cell to another).

Pamrevlumab binds to CTGF, preventing it from binding to cytokines and preventing downstream inflammatory signaling.

Pamrevlumab in clinical trials

A randomized Phase 2b clinical trial (NCT01890265) assigned 103 idiopathic pulmonary fibrosis (IPF) patients to 30 mg per kg of pamrevlumab or to a placebo every three weeks.  Treatment was administered by injection into the bloodstream, for a total of 16 times over 45 weeks. The primary outcome was changes in forced vital capacity (FVC, a measure of how much air a patient can forcibly exhale from their lungs). The progression of lung fibrosis was measured by quantitative high-resolution computed tomography (qHRCT, an imaging technique that uses a series of X-ray images to create a quantitative three-dimensional image of the lungs). Trial results demonstrated that treatment with pamrevlumab slowed the progression of lung fibrosis relative to the placebo group. This lessening in fibrosis progression also correlated with better lung function.

An open-label Phase 2a clinical trial (NCT01262001) also evaluated the safety and tolerability of pamrevlumab in IPF patients, and its effectiveness. Patients received one of two doses, 15 mg per kg or 30 mg per kg, of treatment every three weeks for 45 weeks. Lung function was assessed by measuring FVC, while qHRCT was used to assess fibrosis over the course of the study. Study results were published in the European Respiratory Journal and showed that both dose levels were well-tolerated. Although 65 percent of the 66 people who completed the study showed an increase in lung fibrosis, 35 percent exhibited stable or lesser fibrosis three weeks after the end of treatment (week 48). These benefits were again matched by improvements in lung function.

A randomized Phase 3 clinical trial (NCT03955146) is set but not yet recruiting IPF patients to test the efficacy and safety of 30 mg per kg of pamrevlumab compared to placebo. Patients (565 expected) will be randomly assigned to either pamrevlumab or placebo given as an IV infusion every three weeks over 48 weeks, for a total of 17 treatments. The study’s primary goal is changes in FVC from a patient’s enrollment (baseline measure) out to one year.

 

Last updated: 07/10/2019

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