Trial Data Supporting Safety and Efficacy of FibroGen FG-3019 Idiopathic Pulmonary Fibrosis Drug Presented At ICLAF Colloquium

FibroGen Inc. will present the full data set from a clinical study of patients with Idiopathic Pulmonary Fibrosis (IPF), treated for 48 weeks with the company’s investigational drug FG-3019, at the 18th International Colloquium on Lung and Airway Fibrosis (ICLAF) in progress this week at Mont Tremblant, Quebec — a small resort town located about one hour north of Montreal in the francophone region of Canada, running from Sept 20-24. This meeting brings together leaders, scientists, clinicians, fellows, students and patient advocates in lung fibrosis from around the world.

A poster presentation outlining the FG-3019 research data was displayed September 20, and the oral presentation entitled “Safety and Efficacy of Anti-CTGF Monoclonal Antibody FG-3019 for Treatment of Idiopathic Pulmonary Fibrosis (IPF): Combined Results for Two Cohorts Treated for One Year” will be delivered on Tuesday, September 23, at 2:15pm ET.

IPF is a progressive, irreversible, unpredictable and ultimately fatal disease characterized by progressive scarring (fibrosis) in the lung characterized by a progressive scarring of the lungs that diminishes functional lung volume and hinders oxygen uptake.

FG-3019 is an investigational therapeutic antibody developed by San Diego based biotech firm 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 liver fibrosis, in which the drug has been well tolerated with no apparent safety red flags in more than ten clinical studies and more than 340 treated patients to date.

The ICLAF colloquium was established more than 30 years ago by scientists and clinicians committed to enhance research in fibrosis and to improve care of patients with IPF. This year’s conference will present a wide range of top research in basic and clinical science, and organizers note that 2014 will be a very exciting year for the IPF community and the patients who suffer from this devastating disease, with everyone eagerly awaiting the results and impact of several crucial Phase 3 trials, which will hopefully result in worldwide approval and access to desperately needed IPF drugs.

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In the Fibrogen FG3019 study, lung fibrosis as measured by quantitative high resolution computed tomography (HRCT) was reduced in a substantial portion of patients who received FG-3019. FG-3019 is a monoclonal antibody that inhibits the activity of connective tissue growth factor (CTGF) a central mediator of fibrotic disease.

IPF is a specific type of interstitial lung disease in which the small air sacs of the lung, known as alveoli, gradually become replaced by fibrotic (scar) tissue. The abnormal fibrosis and scar formation typically begins in the terminal areas of the pulmonary tree lining the air sacs where gas exchange occurs. Normally, this tissue is a thin layer consisting of a few, easily permeable cells. With IPF, progressive scarring causes the normally thin and pliable tissue to thicken and become stiff, making it more difficult for the lungs to expand, preventing oxygen from readily getting into the bloodstream.

IPF’s cause is not known (viz. “idiopathic”) and it inevitably leads to worsening lung function and exercise tolerance, and shortness of breath. There is a corresponding increase in respiratory symptoms with dyspnea, air hunger and non-productive cough. Every IPF patient follows a different and unpredictable course and it is not possible to predict if a patient will progress slowly or rapidly, or when the rate of decline may change. Periods of transient clinical stability in IPF, should they occur, inevitably give way to continued disease progression.

IPF is a uniformly fatal disease, with the median estimated survival time from diagnosis two to five years, with a five-year survival rate of approximately 20-40 percent, which makes IPF more rapidly lethal than many cancers, including breast, ovarian, colorectal, pancreatic, lung, and liver cancers. IPF typically occurs in patients over the age of 50, and is more common in men than in women.

Once considered a relatively rare disease, IPF is now recognized as the most common interstitial lung disease (interstitial refers to the tissue surrounding the alveoli). An estimated 50,000-70,000 people are living with IPF in the United States, and approximately 15,000-20,000 new cases are diagnosed annually.It is estimated that between 80,000 and 110,000 patients living with IPF in all of Europe and between 5,000 to 8,000 patients living with IPF in Canada.

The Fibrogen study enrolled patients with a wide range of IPF severity to assess safety and efficacy of FG-3019 across a broad spectrum of the disease. 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 and pulmonary fibrosis. Patients 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 ICLAF presentation provides an updated analysis of efficacy data from all patients treated in the study. Seventy-four (74) patients completed 24 weeks and 66 of these patients completed 48 weeks of treatment and assessment of changes in pulmonary function and pulmonary fibrosis.

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After 24 weeks of treatment 17 of the 74 patients (23%) had improved fibrosis as measured by quantitative HRCT and after 48 weeks of treatment 16 of the 66 patients (24%) had improved fibrosis as measured by quantitative HRCT. FibroGen believes that this is the first trial to demonstrate improved fibrosis in IPF. HRCT is an accurate and reproducible computer-based method to measure fibrotic changes in lung tissue. Fibrogen reports that recent peer-reviewed publications based on similar quantitative HRCT methods have identified an association between worsening pulmonary fibrosis and mortality in IPF (cited: Maldonado et al. Eur Resp J 2014; Oda et al. Respiratory Research 2014), and that studies published to date indicate that in untreated IPF patients fibrosis is at best stable but typically worsens over time.

Changes in fibrosis correlated with changes in forced vital capacity or FVC at 24 weeks (p=0.0001 r= -0.520) and at 48 weeks (p=0.0001 r= -0.591). On average patients with improved or stable fibrosis also had improved pulmonary function at week 24 with FVC change of +0.03 liters compared to -0.15 liters for patients with worsening fibrosis (p=0.0001) and at week 48 with FVC change of +0.04 liters compared to -0.23 liters for patients with worsening fibrosis (p=0.0001) indicating improvement in lung function with improvement in lung fibrosis.

The first dose-cohort enrolled patients with a wide range of disease severity: mild to severe (FVC % predicted 45-85%). In the second dose-cohort enrolment criteria were revised to mild to moderate (FVC % predicted =55%) as most patients with severe disease in cohort 1 dropped out of the trial prior to completion. While an analysis of all patients who completed one year of treatment (N=66) showed a mean FVC change of -0.14 liters mean FVC change for mild to moderate patients at one year (N=60) was -0.11 liters.

Consistent with previously reported interim results FG-3019 was well tolerated in treated patients. All patients experienced at least one adverse event. There were 38 SAEs in 24 patients none of which was considered related to study treatment. Adverse events observed have been consistent with those typically observed in this patient population.

Based on these encouraging data FibroGen is conducting a randomized placebo controlled Phase 2 trial in IPF which is currently enrolling in the US and will soon be expanded to sites outside of the US.

Current FG-3019 Clinical Trials:

FG-3019-067, Phase 2, Idiopathic Pulmonary Fibrosis
– Currently enrolling

FG-3019-049, Phase 2, Idiopathic Pulmonary Fibrosis
– Study ongoing

FG-3019-801, Phase 2, Liver Fibrosis Due to Chronic Hepatitis B Infection
– Currently enrolling

FG-3019-028, Phase 1, Pancreatic Cancer
– Study ongoing

FibroGen is a privately-held biotechnology company focused on the discovery development and commercialization of therapeutic agents for treatment of fibrosis anemia cancer and other serious unmet medical needs. FibroGen’s FG-3019 fully human monoclonal antibody is in clinical development for treatment of idiopathic pulmonary fibrosis and other proliferative diseases including pancreatic cancer and liver fibrosis.

For more information visit:
http://www.fibrogen.com

Sources:
Fibrogen Inc.
18th International Colloquium on Lung and Airway Fibrosis

Image Credit:
Tourisime Mont-Tremblant