dimanche 20 septembre 2020

Gilead Presents Data From Nonalcoholic Steatohepatitis (NASH) Development Program for Advanced Fibrosis at The Liver Meeting® 2018

Par Rédaction , dans Communiqués , le 9 novembre 2018

Friday, November 9th 2018 at 1:00pm UTC

— Phase 2 Data Presented on Investigational FXR Agonist GS-9674
in NASH —

— Enrollment Complete in Phase 2 ATLAS Combination Trial of Three
Investigational Therapies Targeting Distinct Mechanisms of the Disease —

SAN FRANCISCO–(BUSINESS WIRE)– Gilead Sciences, Inc. (Nasdaq: GILD) today announced new data from the
company’s clinical development program for advanced fibrosis due to
nonalcoholic steatohepatitis (NASH). Data presented support the ongoing
development of the company’s investigational compounds, evaluate the
utility of noninvasive tests for the identification of patients with
advanced fibrosis, and demonstrate the significant burden of disease in
affected patients. The data presented across 24 abstracts are being
shared at The Liver Meeting® 2018 in San Francisco this week.

Data from a Phase 2 randomized, placebo-controlled trial of the
investigational, selective, non-steroidal farnesoid X receptor (FXR)
agonist GS-9674 will be presented. In this study, 140 NASH patients were
treated with GS-9674 100 mg, GS-9674 30 mg or placebo orally once daily
for 24 weeks. A decline of at least 30 percent in hepatic fat measured
by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) was
observed in 38.9 percent of patients treated with GS-9674 100 mg
(p=0.011 vs placebo), 14 percent treated with GS-9674 30 mg (p=0.87),
and 12.5 percent with placebo. Improvements in liver biochemistry tests
(serum GGT) and markers of reduced bile acid synthesis (serum C4 and
bile acids) were observed in the 30 mg and 100 mg arms of
GS-9674-treated patients.

GS-9674 was generally well tolerated; moderate to severe pruritus, or
itching, occurred in 14 percent of patients in the GS-9674 100 mg arm
compared to four percent in the GS-9674 30 mg and placebo arms. Changes
in lipid profile and glycemic parameters did not differ between GS-9674
and placebo-treated patients. The most common adverse events in patients
treated with GS-9674 were pruritus, upper respiratory tract infection,
headache and fatigue. Treatment was discontinued due to adverse events
in one patient treated with GS-9674 100 mg (two percent), five patients
treated with GS-9674 30 mg (nine percent), and two patients with placebo
(seven percent).

A separate Phase 2 study (ATLAS) is investigating treatment with
GS-9674, the investigational apoptosis signal-regulating kinase 1
(ASK-1) inhibitor selonsertib, and the investigational acetyl-CoA
carboxylase (ACC) inhibitor GS-0976 alone or in combination, in patients
with advanced fibrosis due to NASH. This randomized, double-blind
52-week study will assess improvement in fibrosis without worsening of
NASH, adverse events and laboratory abnormalities in approximately 350

“We believe our development program is well positioned to address the
unmet need for effective therapies for people living with advanced
fibrosis due to NASH. We are pleased to share that the Phase 2 ATLAS
combination trial of experimental GS-9674, selonsertib, and GS-0976 has
completed enrollment ahead of schedule,” said John McHutchison, AO, MD,
Chief Scientific Officer, Head of Research and Development, Gilead
Sciences. “We also continue to support the liver community in the study
of noninvasive tests to help overcome the risks and limitations of liver
biopsies in the diagnosis of advanced fibrosis due to NASH.”

Noninvasive Tests

In a late-breaker session, Gilead will present an analysis of baseline
data from its Phase 3 STELLAR trials of selonsertib suggesting that the
use of currently available noninvasive tests (NITs) can accurately
identify patients with advanced fibrosis (F3-F4) due to NASH and
potentially reduce the need for liver biopsy. The use of the Fibrosis-4
(FIB-4) index, Enhanced Liver Fibrosis (ELF) test and liver stiffness
measurement by FibroScan® (FS) each demonstrated good
sensitivity and specificity for the discrimination of advanced fibrosis
due to NASH when compared to liver biopsy. When used sequentially, FIB-4
followed by FS or the ELF test accurately identified advanced fibrosis
in 76-81 percent of patients while reducing the frequency of
indeterminate results to as low as 13 percent.

“There is a major need for accurate and readily available tests to
diagnose patients with advanced fibrosis due to NASH, a disease which
affects many aspects of patients’ lives,” said Zobair Younossi, MD, MPH,
FACP, FACG, AGAF, FAASLD, lead study author and Chairman and Professor,
Department of Medicine, Inova Fairfax Hospital. “These findings from the
STELLAR program indicate that currently available noninvasive tools,
when used alone or sequentially, can identify these patients with
advanced fibrosis due to NASH rather accurately, providing a potentially
simple option for physicians to use in clinical practice.

Burden of Disease

Baseline data from patients enrolled in the STELLAR Phase 3 program
presented in a poster session at The Liver Meeting® 2018
demonstrate the significant burden of disease among people with advanced
fibrosis due to NASH. In 1,660 patients enrolled in the STELLAR trials,
patient-reported outcome measures (PROs) were assessed prior to
treatment initiation and compared with population norms. The data
demonstrate that physical health-related PRO scores of NASH patients
were significantly lower than population norms. In addition, patients
with cirrhosis had lower PRO scores than those with bridging fibrosis in
areas including bodily pain, social functioning, and all but one domain
of the disease-specific Chronic Liver Disease Questionnaire (CLDQ) for
nonalcoholic fatty liver disease (NAFLD) and NASH.

In another analysis of patients enrolled in the STELLAR Phase 3 study
presented during a poster session, elevated values of the ELF test and
NAFLD fibrosis score were associated with impairment in PROs, especially
physical health-related scores and the scores captured by the
disease-specific CLDQ-NAFLD/NASH. These data extend prior observations
that noninvasive fibrosis markers may predict fibrosis stage and adverse
clinical outcomes, and now, impairments in health-related quality of
life, in patients with NASH.

GS-9674, selonsertib and GS-0976 are investigational compounds and are
not approved by the U.S. Food & Drug Administration (FDA) or any other
regulatory authority. Their safety and efficacy have not been

About Gilead’s Clinical Programs in NASH

NASH is a chronic and progressive liver disease characterized by fat
accumulation and inflammation in the liver, which can lead to scarring,
or fibrosis, that impairs liver function. Individuals with advanced
fibrosis, defined as bridging fibrosis (F3) or cirrhosis (F4), are at a
significantly higher risk of liver-related mortality.

Gilead is advancing multiple novel investigational compounds for the
treatment of advanced fibrosis due to NASH, evaluating single-agent and
combination therapy approaches against the core pathways associated with
NASH – hepatocyte lipotoxicity, inflammation and fibrosis.
Investigational compounds in development include the ASK1 inhibitor
selonsertib, the selective, non-steroidal FXR agonist GS-9674 and the
ACC inhibitor GS-0976. The STELLAR Phase 3 trial program evaluating
selonsertib among NASH patients with bridging fibrosis (F3) or cirrhosis
(F4) is ongoing. GS-9674 and GS-0976 are currently in Phase 2 studies in

About Gilead Sciences

Gilead Sciences, Inc. is a research-based biopharmaceutical company that
discovers, develops and commercializes innovative medicines in areas of
unmet medical need. The company strives to transform and simplify care
for people with life-threatening illnesses around the world. Gilead has
operations in more than 35 countries worldwide, with headquarters
in Foster City, California. For more information on Gilead Sciences,
please visit the company’s website at www.gilead.com.

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 complete its Phase 2 and Phase 3 clinical trial programs
evaluating single-agent and combination therapy approaches, including
selonsertib, and/or GS-9674 and/or 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, and/or
GS-9674 and/or GS-0976 if, for example, Gilead believes
commercialization will be difficult relative to other opportunities in
its pipeline. As a result, the compounds 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, 2018, 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
follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs
at 1-800-GILEAD-5 or 1-650-574-3000


Gilead Sciences, Inc.
Sung Lee, 650-524-7792
Attridge, 650-425-8975

Source: Gilead Sciences, Inc.

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