-- Results Demonstrate Improvement in
Fibrosis Stage among NASH Patients with Moderate to Severe Fibrosis
--
Gilead Sciences (Nasdaq:GILD) today announced detailed results
from an open-label Phase 2 trial evaluating the investigational
apoptosis signal-regulating kinase 1 (ASK1) inhibitor selonsertib
(formerly GS-4997) alone or in combination with the monoclonal
antibody simtuzumab (SIM) in patients with nonalcoholic
steatohepatitis (NASH) and moderate to severe liver fibrosis
(fibrosis stages F2 or F3). The data demonstrate regression in
fibrosis that was, in parallel, associated with reductions in other
measures of liver injury in patients treated with selonsertib for
24 weeks. These data were presented in a late-breaking abstract
session at The Liver Meeting® 2016 in Boston (#LB-3).
Patients receiving selonsertib demonstrated improvements in
several measures of liver disease severity, including fibrosis
stage, progression to cirrhosis, liver stiffness (measured by
magnetic resonance elastography, MRE) and liver fat content
(measured by magnetic resonance imaging (MRI)-proton density fat
fraction, PDFF). Data for these efficacy endpoints are summarized
in the table below. As no differences were observed between
combination and monotherapy, results are presented for selonsertib
(18 mg and 6 mg) with/without SIM and for SIM alone. Additionally,
patients with fibrosis improvement demonstrated reductions in
hepatic collagen content, liver biochemistry (e.g., serum ALT) and
the apoptosis marker, cytokeratin-18, supporting the biological
activity of selonsertib.
Endpoint (Week 24) Selonsertib
18 mg ± SIM
Selonsertib 6 mg ± SIM
SIM Fibrosis Improvement ≥1 Stage from
Baseline* 43% (n=13/30) 30% (n=8/27) 20% (n=2/10) Progression to
Cirrhosis 3% (n=1/30) 7% (n=2/27) 20% (n=2/10) ≥15% Reduction in
Liver Stiffness by MRE 20% (n=5/25) 32% (n=7/22) 0% (n=0/7) ≥30%
Reduction in Liver Fat by MRI-PDFF 26% (n=8/31) 13% (n=3/24) 10%
(n=1/10)
*Fibrosis staged according to the NASH
Clinical Research Network (CRN) classification by a central
pathologist blinded to treatment group.
Selonsertib demonstrated no dose-related increases in
treatment-emergent adverse events or serious adverse events.
Headache, nausea and sinusitis were the most common adverse events
in patients receiving selonsertib.
“Currently, no approved treatments exists for NASH, and patients
with advanced fibrosis would potentially benefit from new options
to halt and/or reverse the progression of their disease,” said
Rohit Loomba, MD, MHSc, lead study author and Director, NAFLD
Research Center, Director of Hepatology, Professor of Medicine,
Vice Chief, Division of Gastroenterology, University of California
San Diego School of Medicine. “After only 24 weeks of therapy,
selonsertib exhibited promising anti-fibrotic activity in this
study, which was the first known multi-center NASH clinical trial
to use centrally-assessed MRE, MRI-PDFF, in addition to liver
biopsy as endpoints. Based on these data, selonsertib represents an
important investigational drug candidate for further clinical
trials in patients with NASH and significant fibrosis.”
Other Gilead NASH data being presented at The Liver Meeting
include results from Phase 1 studies evaluating the investigational
selective, non-steroidal Farnesoid X receptor (FXR) agonist
GS-9674. Data from a Phase 1 study demonstrated the biological
activity and safety profile of GS-9674 in healthy volunteers and
support the evaluation of this compound in patients with NASH and
cholestatic liver disorders (#1077 and #1140). Phase 2 studies with
GS-9674 are ongoing in patients with NASH, primary biliary
cholangitis (PBC) and primary sclerosing cholangitis (PSC).
Additionally, preclinical data for the combination of
selonsertib and GS-9674 in a rodent model of advanced fibrosis
suggested that the combination of selonsertib and GS-9674 resulted
in greater anti-fibrotic activity than either agent alone (#1588).
These preclinical data support clinical evaluation of combination
approaches with selonsertib and GS-9674 in patients with NASH and
advanced fibrosis.
Selonsertib, GS-9674 and simtuzumab have not been determined to
be safe or efficacious.
About Selonsertib and the
Study
Selonsertib is an investigational small molecule inhibitor of
ASK1, a protein that promotes inflammation, apoptosis (cell death)
and fibrosis in settings of oxidative stress. Oxidative stress can
be increased in many pathological conditions including liver
diseases such as NASH.
This Phase 2, randomized, open-label trial evaluated the safety,
tolerability and efficacy of selonsertib alone or in combination
with SIM in 72 patients with NASH and fibrosis stages F2 (n=25) or
F3 (n=47). Eligible patients were randomized (2:2:1:1:1) to receive
selonsertib 6 mg (n=20), selonsertib 18 mg (n=22), selonsertib 6 mg
plus SIM 125 mg (n=10), selonsertib 18 mg plus SIM 125 mg (n=10) or
SIM 125 mg alone (n=10) for 24 weeks. Selonsertib was administered
orally once daily and SIM was administered via weekly subcutaneous
injection.
About Gilead’s Clinical Programs in
NASH
Gilead is advancing a pipeline of novel investigational
therapies for the treatment of NASH with advanced fibrosis. Gilead
is currently planning or conducting Phase 2 and Phase 3 clinical
trials evaluating single-agent and combination therapy approaches
against multiple core pathways associated with NASH – metabolic
dysfunction, inflammation and fibrosis. Compounds in development
include the ASK1 inhibitor, selonsertib; the FXR agonist, GS-9674;
and an inhibitor of acetyl-coA carboxylase (ACC), GS-0976,
currently being evaluated in a Phase 2 study in patients with
NASH.
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 Gilead’s ability to initiate or complete its Phase 2 and
Phase 3 clinical trial programs evaluating selonsertib, GS-9674 and
GS-0976 in patients with NASH in the currently anticipated
timelines or at all. In addition, there is the possibility of
unfavorable results from further clinical trials involving these
compounds. Further, it is possible that Gilead may make a strategic
decision to discontinue development of selonsertib, GS-9674 and
GS-0976 if, for example, Gilead believes commercialization will be
difficult relative to other opportunities in its pipeline. As a
result, selonsertib, GS-9674 and GS-0976 may never be successfully
commercialized. 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 Quarterly Report on Form 10-Q for
the quarter ended September 30, 2016, 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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Gilead SciencesInvestorsSung Lee, 650-524-7792MediaNathan
Kaiser, 650-522-1853
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