FibroGen P1 in IPF / FG-3019 (anti CTGF)
Competition for CAT/GENZ ... ('Biomaven' is a shareholder...)
SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Dec. 18, 2003--FibroGen, Inc., today announced the initiation of an open-label, Phase 1 clinical trial designed to evaluate the safety and tolerability of FG-3019, the Company's lead investigational anti-fibrotic agent, in patients with idiopathic pulmonary fibrosis (IPF). FG-3019 is designed to delay or halt the progression of fibrotic disease by blocking connective tissue growth factor (CTGF), a protein that plays a key role in fibrosis (excessive and persistent formation of scar tissue).
"The initiation of clinical testing with FG-3019 represents a new and promising direct anti-fibrotic approach to the treatment of IPF," said Pedro R. Urquilla, MD, Vice President of Medical Affairs at FibroGen. "Elevated levels of CTGF are found in lung tissue from patients with IPF, and preclinical studies show that treatment with FG-3019 reduces scarring in animal models of lung fibrosis. Thus, we believe that FG-3019 is a potential first-in-class anti-fibrotic therapy that could halt or delay disease progression and improve lung function in this difficult-to-treat setting."
The Phase 1 clinical trial is an open-label, sequential-group, dose-escalating study expected to enroll up to twenty-seven patients with IPF and designed to evaluate the safety, tolerability, pharmacokinetics, and immunogenicity of FG-3019. Patients will receive one of three escalating dose levels of study material administered as a single, intravenous infusion. The trial will be conducted at four centers in the United States.
"FibroGen was originally founded to discover and develop novel drugs for the treatment of fibrotic disorders. Beginning a Phase 1 clinical trial with FG-3019 is doubly gratifying in that we achieve an important corporate milestone and commence testing of a new anti-fibrotic strategy that we believe holds promise for treating patients with IPF and that addresses a large, unmet medical need for the treatment of numerous fibroproliferative disorders," said Thomas B. Neff, Chief Executive Officer of FibroGen. "This is an important step in our development program for therapeutics that treat chronic fibrosis, which includes plans to initiate clinical studies in diabetic nephropathy, and potentially other forms of renal fibrosis and scleroderma."
About IPF
IPF is a debilitating and life-threatening lung disease characterized by a progressive scarring of the lungs that hinders oxygen uptake. The cause of IPF is not known. As scarring progresses, patients with IPF experience shortness of breath and difficulty with performing routine functions, such as walking and talking. The prevalence of IPF has been estimated to be over 50,000 cases in the U.S., with an annual incidence of approximately 15,000. There are no FDA-approved treatments for IPF, and approximately two-thirds of patients die within five years after diagnosis. Patients are typically treated with anti-inflammatory agents; however, none have been clinically proven to improve survival or quality of life for patients with IPF.
About CTGF and Fibrosis
Fibrosis is a pathological condition in which the normal wound healing process goes awry, culminating in the excessive production and deposition of collagen, a key component of scar tissue. The persistent formation of scar tissue hinders proper tissue function and can lead to organ failure in a wide range of fibrotic diseases. CTGF plays a key role in fibrosis by triggering the production of collagen and is thus an attractive target for anti-fibrotic therapies.
A growing body of clinical evidence supports the role of CTGF in fibrotic disease. Numerous published studies show that CTGF is overexpressed (present in abnormally high amounts) in samples obtained from patients with fibroproliferative disorders of the major organs and tissues including the lungs, skin, kidneys, liver, heart, and eyes. Most recently, at the American Society of Nephrology Annual Meeting, FibroGen and collaborators reported that urine levels of CTGF from patients with Type 2 diabetes and non-diabetic renal diseases predict progression of kidney disease and response to treatment (adjunct therapies, such as ACE's and ARB's).
In IPF, CTGF has been implicated in all levels of the disease from increased CTGF gene expression to elevated levels of CTGF protein in the cells thought to play an active role in the disease. Researchers have reported increased expression of the CTGF gene in transbronchial-biopsy specimens and bronchoalveolar lavage cells. Further, the presence of CTGF protein in lung tissue of IPF patients appears to be confined predominantly to those cell types believed to play a critical role in pulmonary fibrosis (proliferating type II alveolar cells and activated fibroblasts).
Targeting CTGF to inhibit the fibrotic process is supported by independent studies and FibroGen's preclinical work. Generalized sclerosis and specific models of kidney and lung disease were all successfully treated with antibodies targeting CTGF, including a model of bleomycin-induced lung fibrosis.
Other studies show that CTGF is a downstream mediator responsible for the persistent pro-fibrotic effects of transforming growth factor-beta (TGF-beta), indicating the importance of targeting CTGF to treat diseases marked by chronic fibrosis. TGF-beta is a regulatory protein that has multiple functions, including an early role in the inflammatory response to injury and a central role in triggering the chain of events leading to the induction of CTGF and scarring. Due to its specialized role in perpetuating the scarring process, CTGF could be a more specific target for anti-fibrotic therapies, which could provide significant clinical benefit without broad side effects.
About FG-3019
FG-3019, a fully human monoclonal antibody directed against CTGF, is FibroGen's lead investigational anti-fibrotic therapy designed to bind, neutralize, and clear CTGF from the body. In animal models of lung, kidney, and systemic fibrosis including heart and liver, treatment with FG-3019 reduces scar tissue formation and preserves organ structure and function.
About FibroGen
FibroGen, Inc., is a privately held biotechnology company focused on the discovery, development, and commercialization of therapeutics, recombinant human collagens, and recombinant gelatins to address unmet needs in the medical, pharmaceutical, and consumer markets. FibroGen's therapeutic target areas include fibrosis, anemia, ischemia, and dermal augmentation.
For more information about FibroGen, Inc., please visit www.fibrogen.com. |
