April 16, 2016
Gilead Presents New Data Highlighting Progress in Liver Fibrosis
– Data Support Ongoing Study of Simtuzumab, GS-4997 and GS-9674,
Investigational Compounds for the Treatment of NASH and PSC –
FOSTER CITY, Calif.--(BUSINESS WIRE)--Apr. 16, 2016--
Gilead Sciences, Inc. (NASDAQ:GILD) today announced data supporting the
development of three investigational agents for the treatment of
nonalcoholic steatohepatitis (NASH) and primary sclerosing cholangitis
(PSC). The data were presented in oral and poster sessions at The
International Liver CongressTM 2016 in Barcelona, Spain.
NASH is a serious liver disease resulting from metabolic dysfunction
that is associated with steatosis (fat within the liver), inflammation
and fibrosis, which may progress to cirrhosis. NASH-related cirrhosis is
expected to become the leading indication for liver transplantation by
2020. PSC is a disease characterized by inflammation and stricturing of
the bile ducts. PSC can eventually lead to cirrhosis and other
complications, including bile duct cancer.
“The data presented enhance our understanding of the pathogenesis of
NASH and PSC – two progressive liver diseases for which there are no
approved treatment options,” said Norbert Bischofberger, PhD, Executive
Vice President of Research and Development and Chief Scientific Officer
at Gilead. “We are committed to advancing the treatment of NASH and PSC
by targeting multiple core pathways associated with metabolic
dysfunction, inflammation and fibrosis. We are encouraged by the data
presented at EASL and look forward to applying the scientific insights
from these and other ongoing studies to enhance our clinical programs.”
Simtuzumab is a monoclonal antibody that is selective for lysyl
oxidase-like-2 (LOXL2), an extracellular matrix enzyme that promotes
fibrosis via the cross-linkage of collagen fibers. Gilead is evaluating
simtuzumab for the treatment of fibrosis in patients with NASH and PSC
in three ongoing Phase 2b clinical trials.
Data evaluating the associations between clinical features, liver
histology and portal pressure at baseline in patients with NASH and PSC
were presented in multiple poster sessions (Poster THU-016, Poster
THU-369, Poster FRI-324, Poster FRI-350, Poster FRI-375 and Poster
SAT-400). The data support the correlations between PSC-related liver
fibrosis assessed histologically and noninvasive markers (e.g., serum
levels of LOXL2 and liver stiffness by transient elastography).
An additional study presented during an oral session identified novel
genetic polymorphisms associated with liver fibrosis and serum levels of
LOXL2 in patients with PSC, which may help identify patients with an
increased risk of disease progression (Oral PS-093).
These studies were led by Christopher Bowlus, MD, University of
California, Davis, Sacramento, California (FRI-375); Zachary Goodman,
MD, PhD, Inova Fairfax Hospital, Falls Church, Virginia (SAT-400);
Andrew Muir, MD, Duke Clinical Research Institute, Durham, North
Carolina (FRI-350); Arun Sanyal, MD, Virginia Commonwealth University,
Richmond, Virginia (THU-016); and Patrick Shea, PhD, Institute for
Genomic Medicine at Columbia University, New York, New York (THU-369;
FRI-324; Oral PS-093).
Topline safety and efficacy data from the Phase 2b studies of simtuzumab
for the treatment of NASH and PSC are anticipated by the end of 2016.
GS-4997 is a small-molecule inhibitor of apoptosis signal-regulating
kinase 1 (ASK1), which promotes inflammation, apoptosis and
fibrosis in settings of increased oxidative stress associated with NASH
pathogenesis. GS-4997 is currently being evaluated in an ongoing Phase 2
study in patients with NASH and moderate to severe liver fibrosis.
Results from a Gilead-led preclinical study presented during an oral
session (Oral PS-070) demonstrate that GS-444217, a related ASK1
inhibitor, significantly reduced hepatic steatosis, inflammation,
fibrosis, serum cholesterol and insulin resistance in mice fed a diet
high in fat, cholesterol and sugar. In addition, ASK1 inhibition led to
significant changes in plasma metabolites related to bile acid and lipid
GS-9674 is a selective, non-steroidal agonist of the Farnesoid X
receptor (FXR), a nuclear hormone receptor that is highly expressed in
the gastrointestinal tract and liver. FXR is the primary regulator of
bile acid synthesis and plays important roles in glucose and lipid
metabolism. Results from two preclinical studies selected for oral
presentation highlight the therapeutic efficacy of GS-9674 in animal
models of NASH. In a Gilead-led study, a diet-induced obesity model
demonstrated that mice administered GS-9674 had reduced hepatic
steatosis and fibrosis, as well as serum levels of cholesterol, ALT and
AST compared with untreated animals (Oral PS-066).
In a second study, presented by Philipp Schwabl, MD, and led by Michael
Trauner, MD, both of the Division of Gastroenterology and Hepatology,
Department of Internal Medicine III, Medical University of Vienna,
Vienna, Austria, rats were administered sodium nitrate and fed a
choline-deficient, high-fat diet for 10 weeks that resulted in cirrhosis
and portal hypertension. Data demonstrate that GS-9674 treatment had
dose-dependent anti-fibrotic effects and lowered portal pressure (Oral
PS-058). The results of these pre-clinical studies support the
evaluation of GS-9674 in patients with NASH following completion of an
ongoing Phase 1 study.
Acetyl-CoA Carboxylase (ACC) Inhibitor NDI-010976
As announced on April 4, Gilead entered into an agreement to acquire the
Acetyl-CoA Carboxylase (ACC) inhibitor program from Nimbus Therapeutics,
which includes the clinical compound NDI-010976 and a number of other
preclinical ACC inhibitors for the potential treatment of NASH,
hepatocellular carcinoma (HCC) and other diseases. The acquisition is
subject to certain closing conditions, including receipt of U.S.
antitrust approval. Nimbus presented Phase 1 data (Oral PS-108) showing
that NDI-010976 inhibited de novo lipogenesis in a dose-dependent
Further information about the clinical studies described above can be
found at www.clinicaltrials.gov.
Simtuzumab, GS-4997, GS-9674 and NDI-010976 are investigational products
and have not been determined to be safe or efficacious.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops
and commercializes innovative therapeutics in areas of unmet medical
need. The company’s mission is to advance the care of patients suffering
from life-threatening diseases. Gilead has operations in more than 30
countries worldwide, with headquarters in Foster City, California.
This press release includes forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995 that are
subject to risks, uncertainties and other factors, including the risk
that Gilead may observe unfavorable results from additional clinical
trials involving simtuzumab, GS-4997, GS-9674 and NDI-010976 and
Gilead’s acquisition of Nimbus’s ACC inhibitor program may not be
completed since the transaction is subject to closing conditions. In
addition, Gilead may make a strategic decision to discontinue
development of simtuzumab, GS-4997, GS-9674 and NDI-010976 if, for
example, Gilead believes commercialization will be difficult relative to
other opportunities in its pipeline. These risks, uncertainties and
other factors could cause actual results to differ materially from those
referred to in the forward-looking statements. The reader is cautioned
not to rely on these forward-looking statements. These and other risks
are described in detail in Gilead’s Annual Report on Form 10-K for the
year ended December 31, 2015, as filed with the U.S. Securities and
Exchange Commission. All forward-looking statements are based on
information currently available to Gilead, and Gilead assumes no
obligation to update any such forward-looking statements.
For more information on Gilead Sciences, please visit the company’s
website at www.gilead.com,
follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs
at 1-800-GILEAD-5 or 1-650-574-3000
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Source: Gilead Sciences, Inc.
Gilead Sciences, Inc.
Patrick O’Brien, 650-522-1936