FibroGen Reports Combinations of FG-3019 plus ACEi and FG-3019 Plus
ARB Prevented and Reversed Arterial Stiffness Significantly Better than
ACEi or ARB Alone in Preclinical Models of Diabetes
Data presented at the 66th Annual Scientific Sessions of the American
Diabetes Association
Washington, DC - June 12, 2006 - FibroGen, Inc. today
announced that administration of FG-3019 alone, or in combination with
angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor
blocker (ARB), was significantly better in preventing and reversing
arterial stiffness than ACEi or ARB therapy alone in preclinical
models of diabetes. In addition, FG-3019 prevented cardiovascular
dysfunction and prevented and reversed edema (swelling due to leakage from
microvasculature). The data were presented at the 66th Annual Scientific
Sessions of the American Diabetes Association (Abstract #513-P). FG-3019,
the Company's investigational therapeutic antibody against connective
tissue growth factor (CTGF), is currently the subject of a phase 1b
study in diabetic patients with microalbuminuria (early-stage kidney
disease).
Cardiovascular disease is the leading cause of death among individuals
with diabetes, accounting for at least two-thirds of diabetes-related
deaths. Risk of death from heart disease or stroke among diabetics is
two to four times greater than for those without diabetes.
"These studies suggest that FG-3019 protects blood vessels of the heart
and periphery from damage caused by diabetes," said David Y. Liu, Ph.D.,
Vice President of Research at FibroGen. "Importantly, FG-3019 appears
to address pathways not affected by ACEi or ARB therapy, suggesting
that combining anti-CTGF therapy with anti-hypertension medications may
improve cardiovascular outcomes in patients with diabetes."
FibroGen presented data from multiple studies designed to examine the
effects of FG-3019 alone and in combination with current therapeutics,
captopril (ACEi) and losartan (ARB), on diabetic vascular and cardiac
complications including arterial passive stiffness, cardiac dysfunction,
and vascular permeability. Type 1 diabetes was induced in rats by
injection of streptozotocin (STZ), which destroys the insulin-producing
islet cells of the pancreas.
After six weeks of treatment with IgG (control antibody) or captopril,
diabetic rats showed increases in arterial stiffness as measured by
circumferential stiffening of the carotid artery (the ability of the
artery to expand in response to increases in pressure) compared to
non-diabetic control mice. In contrast, diabetic rats treated with
FG-3019 did not show significant increases in arterial stiffness and
remained similar to healthy control animals.
In a subsequent study, when STZ-injected rats were left untreated for six
weeks, allowing diabetes and associated vascular pathologies to first be
established, and then treated for six more weeks, results demonstrated
that FG-3019 was significantly better than either captopril (p<0.01)
or losartan (p<0.05) in preventing arterial stiffening. In addition,
combinations of FG-3019 with captopril or losartan were better than
captopril (p<0.01) or losartan therapy (p<0.01) alone, and significantly
reversed arterial stiffening (p<0.05) to levels not different from healthy
controls. Measurements of ejection fraction and end diastolic pressure
indicated that FG-3019 therapy prevented cardiac dysfunction. FG-3019
also prevented diabetes-induced leakage from blood vessels in the skin
and associated edema whereas captopril did not. In the follow-up study,
neither captopril nor losartan prevented diabetes-induced vascular
leakage.
"Previous research in preclinical models has demonstrated the benefit
of using FG-3019 to treat diabetic kidney disease, and these new
findings extend the potential therapeutic utility of FG-3019 to diabetic
cardiovascular disease," said Thomas B. Neff, Chief Executive Officer
at FibroGen. "These results are particularly relevant as we continue to
develop FG-3019 in the setting of diabetic nephropathy where the vast
majority of patients die of cardiovascular disease before reaching
renal failure. FG-3019 shows potential to be a novel therapeutic for
diabetic nephropathy that may provide additional benefit in improving
cardiovascular outcomes beyond current therapies. In addition, FG-3019
uniquely addresses other complications, such as vascular leakage, which
are non-responsive to current therapies."
About FG-3019
FG-3019 is an investigational fully human monoclonal antibody against
CTGF. In a phase 1 study of FG-3019 in patients with idiopathic
pulmonary fibrosis, FG-3019 was found safe and well tolerated. Currently,
FG-3019 is the subject of a phase 1b study in diabetic patients with
microalbuminuria. In preclinical models, FG-3019 has been shown to block
fibrosis in the lung, kidney, heart, liver, and intestines, and decrease
proteinuria while improving renal function.
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, ischemic disease, 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 FibroGens proprietary cosmetic dermal filler and
biomaterials supply business.
For more information about FibroGen, Inc., please visit
www.fibrogen.com.
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Contact:
Laura Hansen 650-866-7828 or lhansen@fibrogen.com