– Data Support Ongoing Study of Simtuzumab,
GS-4997 and GS-9674, Investigational Compounds for the Treatment of
NASH and PSC –
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
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
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 metabolism.
GS-9674
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 fashion.
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.
Forward-Looking
Statement
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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version on businesswire.com: http://www.businesswire.com/news/home/20160416005003/en/
Gilead Sciences, Inc.InvestorsPatrick O’Brien,
650-522-1936MediaCara Miller, 650-522-1616
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