FibroGen Reports Preclinical Data Showing that FG-3019 Reversed the Process of Fibrosis in the Lung

— Lung Function and Survival Improved in Model of Radiation-Induced Lung Fibrosis —

— FibroGen Pursues Human Trials in Fibrosis and Pancreatic Cancer —

NEW ORLEANS--(BUSINESS WIRE)--May 17, 2010 - FibroGen, Inc. today announced that administration of investigational therapy FG-3019, a human monoclonal antibody against connective tissue growth factor (CTGF), reversed the process of fibrosis in a preclinical model of radiation-induced lung fibrosis, a finding that has implications for treating multiple types of fibrotic disease. Administration of FG-3019 was also found to improve lung function and survival in this model. The data were presented at the International Conference of the American Thoracic Society in New Orleans (Abstract #A1054).

“This is the first time a therapeutic agent has demonstrated the ability to reverse the process of lung fibrosis in this model,” said Professor Peter Huber, Head of the Radiation Oncology Division at the German Cancer Research Center (DKFZ), Heidelberg, Germany, where the study was conducted. “The finding that lung function and survival were improved even when administration of FG-3019 was delayed until after the development of significant pathology and initiation of the fibrotic process suggests that FG-3019 could be used therapeutically to reverse fibrotic damage to the lung.”

“There is a serious unmet need for the development of effective therapies to treat fibrotic disease of the lungs and other vital organs,” said Kevin Flaherty, MD, Associate Professor in the Department of Internal Medicine at the University of Michigan Health System. “These are encouraging data and support studying the ability of FG-3019 not only to slow, but to reverse, the progression of fibrotic lung disease.”

FG-3019 Activity in Model of Radiation-Induced Fibrosis: Study Results

This model of radiation-induced lung fibrosis closely represents progressive lung damage in humans in which initial inflammatory stages are followed by extensive tissue remodeling and scar formation. In this 48-week study, mice (n=25 per group) were given a lethal dose of radiation, and treated groups were administered FG-3019 either prior to irradiation (5 days before) or at various time points after irradiation (starting 2 days, 3 weeks, or 16 weeks after irradiation) or given placebo antibody. In the groups of mice that were irradiated but untreated, lung density steadily increased during the course of the study indicating progressive impairment of lung function. In contrast, in all irradiated groups treated with FG-3019, progression of increasing lung density was attenuated. Moreover, a significant reversal of this fibrotic process was observed in the group that started FG-3019 therapy at 16 weeks post-irradiation.

Examination of lung tissue showed that treatment with FG-3019 attenuated extensive remodeling and fibrosis that were evident in untreated and control groups at 30 weeks after irradiation. In the groups treated with FG-3019 starting at 3 or 16 weeks post-irradiation, no remodeling or fibrosis was observed at 30 weeks, and lung function, as measured by arterial oxygen partial pressure, was normalized in these groups. Survival was also improved by treatment with FG-3019. The best survival was observed in the group administered FG-3019 starting 3 weeks after irradiation in which 70% were still alive at the end of the study (at 48 weeks post-irradiation) versus no survivors in the groups that were irradiated but left untreated or treated with a placebo antibody.

Pioneering Anti-Fibrosis Therapies: Moving Towards Proof-of-Principle in Humans

“FibroGen was founded to discover and develop first-in-class anti-fibrosis therapeutics and has worked steadily since inception to characterize the actions of CTGF and develop safe methods of blocking CTGF action,” said Thomas B. Neff, Chief Executive Officer of FibroGen. “Although we have seen suggestions from other nonclinical studies that CTGF blockade may reverse liver fibrosis and diabetes-induced arterial stiffening, these new results achieved in a model as rigorous as radiation-induced lung fibrosis give us increased confidence that FG-3019 can reverse fibrosis.”

FibroGen is now exploring the potential for FG-3019 to reverse fibrosis and delay disease progression in humans. FG-3019 has been well tolerated in a phase 1 study of patients with idiopathic pulmonary fibrosis and in two phase 1 studies of patients with diabetic kidney disease. The phase 2 clinical program involves proof-of-principle studies in renal, cardiovascular, hepatic, and pulmonary fibrotic conditions with the goal of generating data that will inform the direction of a pivotal trial program for FG-3019. The first phase 2 study began in May 2009 in patients with diabetes in which the impact of FG-3019 on renal function and on cardiovascular co-morbidities is being evaluated. The second study, expected to begin in the summer, will evaluate FG-3019 in patients with advanced liver fibrosis caused by HBV who are initiating anti-viral therapy with entecavir and will compare outcomes with and without FG-3019. A third study focused on patients with interstitial pulmonary fibrosis will be announced later this year.

Going Beyond Fibrosis: FG-3019 Shows Promise in Treating Pancreatic Cancer

“Approximately a decade ago, FibroGen recognized that CTGF is involved in pancreatic cancer in ways beyond fibrotic actions, and we have systematically studied this relationship,” said Mr. Neff. “Preliminary observations from our ongoing phase 1 study of FG-3019 in patients with pancreatic cancer suggest that FG-3019 may have the ability to alter disease progression in Stage III and Stage IV patients.”

A growing body of data, including research from independent academic laboratories, suggests a direct role for CTGF in pancreatic tumor growth, metastasis, and disease progression.1-8 Planned enrollment has been completed in the open-label, dose-escalation phase 1 trial of FG-3019 in patients with advanced pancreatic cancer, which is being conducted at Stanford University School of Medicine, Stanford, CA, and at Dartmouth Hitchcock Medical Center, Lebanon, NH.

“At the request of our collaborators, we have expanded and extended the clinical study to establish the tolerability of higher doses of FG-3019,” said Mr. Neff. “Results to date suggest that doses of FG-3019 higher than those that seem to be required in fibrosis may lead to better outcomes in pancreatic cancer, which is consistent with potentially different actions of CTGF in these settings. We plan to initiate studies in patients with pancreatic cancer who are refractory to gemcitabine in the third quarter of this year. We will initiate randomized studies thereafter.”

About FibroGen

FibroGen, Inc. is a biotechnology-based drug discovery company using its expertise in the fields of tissue fibrosis, connective tissue growth factor (CTGF), and hypoxia-inducible factor (HIF) biology to discover, develop, and commercialize novel therapeutics for fibrotic disorders, diabetic complications, anemia, conditions associated with tissue damage or injury, cancer, and other areas of unmet medical need. FibroGen also develops and produces recombinant human collagens and gelatins using unique production technology that provides the basis for FibroGen's proprietary cosmetic dermal filler and biomaterials supply business.

For more information about FibroGen, Inc., please visit www.fibrogen.com.

 

References

1. Wenger C, et al. Expression and differential regulation of connective tissue growth factor in pancreatic cancer cells. Oncogene 1999; 18:1073-1080.

2. Iacobuzio-Donahue CA, et al. Exploring the host desmoplastic response to pancreatic carcinoma: gene expression of stromal and neoplastic cells at the site of primary invasion. Am J Pathol. 2002 Jan;160(1):91-9.

3. Ryu B, et al. Invasion-specific genes in malignancy: serial analysis of gene expression comparisons of primary and passaged cancers. Cancer Res. 2001; 61:1833-1838.

4. Burns WC, et al. Connective tissue growth factor plays an important role in advanced glycation end product-induced tubular epithelial-to-mesenchymal transition: implications for diabetic renal disease. J Am Soc Nephrol. 2006 Sep;17(9):2484-94.

5. Yang J and Weinberg RA. Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell. 2008 Jun;14(6):818-29.

6. Bennewith K, et al. The role of tumor-derived connective tissue growth factor (CTGF/CCN2) in pancreatic tumor growth. Cancer Res 2009; 69:775-784.

7. Dornhöfer N, et al. Connective tissue growth factor specific mAb therapy inhibits pancreatic tumor growth and metastasis. Cancer Res. 2006; 66:5817-27.

8. Aikawa T, et al. Connective tissue growth factor specific antibody attenuates tumor growth, metastasis and angiogenesis in an orthotopic mouse model of pancreatic cancer. Mol. Cancer Ther. 2006 May;5(5):1108-16.

 

Contact: FibroGen, Inc.
Laura Hansen, Ph.D., 650-455-7934 (on site)
Director, Corporate Communications
lhansen@fibrogen.com

 

Posted: May 2010

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