Fibrogen looks to challenge leaders in IPF

Biotech company Fibrogen wants to play as part in a new era of treating idiopathic pulmonary fibrosis, a lung disease which currently kills most sufferers within five years of diagnosis.

Until recently, there have been no licensed treatments for idiopathic pulmonary fibrosis (IPF), but Shionogi and InterMune's pirferidone became the first ever drug approved to treat the disease in 2011.

The drug, known as Esbriet, was approved in Europe and other markets outside the US, but was refused FDA approval because of doubts about is efficacy and safety. Now pirfenidone is under review by the FDA and it and Boehringer Ingelheim's rival, nintedanib, are neck and neck in their bid to be first to launch in the US.

Both drugs are currently being reviewed by the FDA after having been granted a 'Breakthrough Therapy' fast-track review in July. If approved, the drugs are likely to hit the market in the first quarter of 2015.

San Francisco-based Fibrogren is a privately held company, and is some way behind its two bigger rivals with its treatment, FG-3019.

The firm released new data on Saturday for its treatment for idiopathic pulmonary fibrosis, which showed FG-3019 reduced fibrosis in the lung and improved forced vital capacity (FVC), a measure of lung capacity which deteriorates rapidly in IPF.

Fibrogen is trying to find a clinical trump card for its candidate, and has included in its trials a precise measurement of the progression (or otherwise) of the actual fibrosis as well as FVC, which its rivals have not done.

The open label study used quantitative high resolution computed tomography (HRCT) to pinpoint the effect of the drug on the fibrosis in the patients' lungs.

FG-3019 is a monoclonal antibody that inhibits the activity of connective tissue growth factor (CTGF), a central mediator of fibrotic disease. The data were presented in oral and poster presentations at the 18th International Colloquium on Lung and Airway Fibrosis (ICLAF).

Despite the company's interesting approach to pinpointing disease progression, its phase 2 open label study cannot rival the larger clinical trial programmes of InterMune and Boehringer, both of which also have secondary endpoints focused on impact on mortality rates.

Instead, Fibrogen's new 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.

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.

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.

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 litres compared to -0.15 litres for patients with worsening fibrosis (p=0.0001), and at week 48 with FVC change of +0.04 liters compared to -0.23 litres for patients with worsening fibrosis (p=0.0001), indicating improvement in lung function with improvement in lung fibrosis.

FibroGen says that this data supports it plan to proceed to a randomised placebo controlled Phase 2 trial in IPF, currently enrolling in the US and soon be expanded to sites outside the US.

This trial must produce strong efficacy data if FG-3019 is to play a significant role in the burgeoning IPF market.

Other companies are also active in the field: Biogen's STX-100 and Gilead's simtuzumab, are two monoclonal antibodies also in development.

Other fibrosis trials underway

FG-3019 targets connective tissue growth factor (CTGF), a common factor in chronic fibrotic and proliferative disorders characterised by persistent and excessive scarring that can lead to organ dysfunction and failure. As well as its IPF trials, FibroGen is currently conducting clinical studies of FG-3019 in pancreatic cancer and liver fibrosis. FG-3019 has been well tolerated, with no apparent safety signals, in more than ten clinical studies and more than 340 treated patients to date.

Fibrogren has one other molecule in development: roxadustat (FG-4592), FibroGen's small molecule inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase, for the treatment of anaemia. The company is also pursuing the use of proprietary recombinant human type III collagens in synthetic corneas for treatment of corneal blindness.