-- GS-4997 Demonstrates Anti-Fibrotic
Activity in Open-Label Phase 2 NASH Study; Data Support Plans to
Advance GS-4997 into Phase 3 Clinical Trials --
Gilead Sciences, Inc. (Nasdaq:GILD) today announced the top-line
results from three Phase 2 studies of GS-4997 (selonsertib), an
investigational inhibitor of apoptosis signal-regulating kinase 1
(ASK1), in nonalcoholic steatohepatitis (NASH), pulmonary arterial
hypertension (PAH) and diabetic kidney disease (DKD). GS-4997
demonstrated anti-fibrotic activity in an open-label Phase 2
clinical trial that included 72 patients with NASH and moderate to
severe (F2-F3) liver fibrosis, who received treatment with GS-4997
(18 mg or 6 mg orally once daily) alone or in combination with
simtuzumab (SIM), an investigational antibody directed against
lysyl oxidase-like-2 (LOXL2), or SIM alone (125 mg administered via
weekly subcutaneous injections) for 24 weeks. Top-line efficacy
data for fibrosis-related endpoints from 67 evaluable patients are
summarized in the table below. Complete results will be presented
at The Liver Meeting® 2016 in Boston.
Endpoint (Week 24)
GS-4997 18 mg± SIM
GS-4997 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)
*Fibrosis staged according to the NASH Clinical
Research Network (CRN) classification by a central pathologist
blinded to treatment group.
Overall, GS-4997 was well tolerated with no dose-related
increase in the incidence of treatment-emergent adverse events or
serious adverse events. The most common adverse events were
headache, nausea and sinusitis.
“We are committed to advancing our pipeline of investigational
molecules that separately target metabolic dysfunction,
inflammation and/or fibrosis associated with NASH,” said Norbert
Bischofberger, PhD, Executive Vice President, Research and
Development and Chief Scientific Officer, Gilead Sciences. “We are
encouraged by these data demonstrating the anti-fibrotic effect of
GS-4997 in patients with NASH after only 24 weeks of treatment, and
look forward to sharing the complete results with the hepatology
community. Additionally, pending discussions with regulatory
agencies, we plan to initiate a Phase 3 clinical trial program of
GS-4997 in patients with NASH.”
Separately, a Phase 2 study of GS-4997 in PAH did not achieve
its primary endpoint and a Phase 2 study in DKD did not achieve its
primary endpoint based on a preliminary analysis. Due to
insufficient evidence of efficacy, Gilead has decided not to pursue
Phase 3 studies of GS-4997 in PAH or DKD at this time. Data from
these studies will be submitted for presentation at upcoming
scientific conferences.
About the GS-4997 Phase 2
Studies
Study GS-US-384-1497 was a Phase 2, randomized, open-label
clinical trial designed to evaluate the safety, tolerability and
efficacy of GS-4997 alone or in combination with simtuzumab in 72
patients with NASH and fibrosis stages F2-F3. Eligible patients
were randomized (2:2:1:1:1) to receive GS-4997 6 mg (n=20), GS-4997
18 mg (n=22), GS-4997 6 mg plus simtuzumab 125 mg (n=10), GS-4997
18 mg plus simtuzumab 125 mg (n=10) or simtuzumab 125 mg alone
(n=10) for 24 weeks. GS-4997 was administered orally once daily and
simtuzumab was administered via weekly subcutaneous injection.
Since no differences were observed between combination and
monotherapy, data in the table above are presented by GS-4997
treatment group only.
Study GS-US-223-1015 was a Phase 2 double-blind,
placebo-controlled, dose-ranging study evaluating the efficacy,
safety and tolerability of GS-4997 in 334 patients with type 2
diabetes mellitus and Stage 3 or 4 renal impairment and
albuminuria. Eligible patients were randomized (1:1:1:1) to receive
GS-4997 doses of 2 mg (n=81), 6 mg (n=84), 18 mg (n=84) or matching
placebo (n=85) once daily on top of DKD background therapy for 48
weeks. The primary endpoint was change in estimated glomerular
filtration rate (eGFR) from baseline at Week 48.
ARROW was a Phase 2, dose-ranging, randomized, double-blind,
placebo-controlled study designed to determine the safety, efficacy
and tolerability of three doses of GS-4997 in 151 patients with PAH
(WHO Group 1). Patients were randomized (1:1:1:1) to receive
placebo or GS-4997 doses of 2 mg, 6 mg or 18 mg administered once
daily on top of stable PAH therapy. The primary endpoint was change
from baseline versus placebo in pulmonary vascular resistance (PVR)
at Week 24, as measured by right heart catheterization.
Further information about these studies can be found at
www.clinicaltrials.gov.
GS-4997 and simtuzumab are investigational products and have not
been determined to be safe or efficacious.
About GS-4997
GS-4997 is an investigational small molecule inhibitor of
apoptosis signal-regulating kinase 1 (ASK1), a protein that
promotes inflammation, apoptosis (cell death) and fibrosis in
settings of oxidative stress. Oxidative stress normally occurs at
low levels in healthy states, but can be increased in many
pathological conditions such as NASH.
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.
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 its Phase 3 clinical trial
program evaluating GS-4997 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 GS-4997, including in patients with NASH. Further, it is
possible that Gilead may make a strategic decision to discontinue
development of GS-4997 if, for example, Gilead believes
commercialization will be difficult relative to other opportunities
in its pipeline. As a result, GS-4997 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 June 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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version on businesswire.com: http://www.businesswire.com/news/home/20161020005935/en/
Gilead Sciences, Inc.InvestorsSung Lee,
650-524-7792orMediaNathan Kaiser, 650-522-1853
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