— New Proof-of-Concept Data for Combination of Investigational
FXR Agonist Cilofexor and ACC Inhibitor Firsocostat in NASH —
FOSTER CITY, Calif.–(BUSINESS WIRE)–Gilead Sciences, Inc. (Nasdaq: GILD) today announced new data from the
company’s clinical research program in nonalcoholic steatohepatitis
(NASH) being presented at The International Liver Congress™ 2019 in
Vienna. The data support Gilead’s efforts to develop combination
therapies to target different aspects of NASH, evaluate the utility of
noninvasive tests for the identification of patients living with the
disease and advance overall understanding of the complexities and burden
of NASH.
“NASH is a complex disease with multiple biological pathways that
influence its progression. Combination therapeutic approaches which
target these pathways, are likely to be needed to effectively treat
patients living with NASH, particularly those with advanced fibrosis who
have the greatest unmet need,” said John McHutchison, AO, MD, Chief
Scientific Officer, Head of Research and Development, Gilead Sciences.
“We are encouraged by the results of our proof-of-concept study being
presented this week and look forward to sharing further combination data
from the Phase 2 ATLAS trial later this year.”
Combination Therapy Treatment for NASH
A proof-of-concept study demonstrated that the combination of the
investigational, selective, non-steroidal farnesoid X receptor (FXR)
agonist cilofexor (GS-9674) and the acetyl-CoA carboxylase (ACC)
inhibitor firsocostat (GS-0976) resulted in improvements in hepatic
steatosis, liver stiffness, liver biochemistry and serum fibrosis
markers. In the study, 20 patients with NASH received cilofexor 30 mg
and firsocostat 20 mg orally once daily for 12 weeks. A significant
decline of at least 30 percent in hepatic fat measured by magnetic
resonance imaging-proton density fat fraction (MRI-PDFF) from baseline
to 12 weeks was observed in 74 percent of patients. Improvements in
liver biochemistry tests including serum ALT (median relative reduction,
-37%; p<0.001) and GGT (-32%; p<0.001), along with markers of reduced
bile acid synthesis, were observed at 12 weeks. Treatment was well
tolerated and pruritus was not reported in any patients. Asymptomatic,
Grade 3 hypertriglyceridemia was observed in two patients. No patients
withdrew from the study due to adverse events.
Noninvasive Tests
Liver biopsy is currently the reference standard to identify patients
with NASH but is an invasive and costly procedure with potential for
serious complications. Gilead will present an analysis of screening data
from its Phase 2 ATLAS study evaluating combinations of investigational
cilofexor, firsocostat and selonsertib in advanced fibrosis due to NASH.
This analysis demonstrates that the use of currently available
noninvasive tests (NITs) can accurately identify patients with advanced
fibrosis due to NASH and potentially reduce the need for liver biopsy.
When used in combination, the Enhanced Liver Fibrosis (ELF) test and
FibroScan® accurately identified advanced fibrosis in >80 percent of
patients.
Cilofexor and firsocostat, alone or in combination, are investigational
compounds and are not approved by the U.S. Food & Drug Administration
(FDA) or any other regulatory authority. Safety and efficacy have not
been established for these agents.
Burden of Disease and Patient-Reported Outcomes
While NASH can have non-specific symptoms, research is needed to
understand the impact of disease on quality of life for those living
with the condition, measured through patient-reported outcomes (PROs).
Baseline data from the STELLAR Phase 3 trials showed significant burden
of disease among people with advanced fibrosis due to NASH. In 1,667
patients enrolled in the STELLAR trials, PROs assessed using tools
including the Chronic Liver Disease Questionnaire (CLDQ-NASH) prior to
treatment, particularly those related to physical health-related scores,
were significantly lower than those of population norms. In another
analysis of patients enrolled in the STELLAR program, diabetes mellitus
was associated with impairment in PROs including physical functioning,
bodily pain, general health and vitality. An additional study assessing
health-related quality of life in 1,338 patients with advanced fibrosis
due to NASH demonstrated that these individuals have more impairment of
their physical health-related scores than patients with chronic
hepatitis C virus.
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 living with
fibrosis are at a significantly higher risk of liver-related mortality
and all-cause 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 cilofexor
(GS-9674) and the ACC inhibitor firsocostat (GS-0976). The STELLAR-3
Phase 3 trial evaluating selonsertib among NASH patients with bridging
fibrosis (F3) is ongoing. Cilofexor and firsocostat are currently in
Phase 2 studies in NASH, including the ATLAS trial evaluating
combinations of selonsertib, cilofexor and firsocostat in advanced
fibrosis (F3 and F4) due to NASH.
Selonsertib is an investigational compound and is not approved by the
U.S. Food & Drug Administration (FDA) or any other regulatory authority.
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 clinical trial programs evaluating single-agent
and combination therapy approaches, including selonsertib, cilofexor
and/or firsocostat, 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, cilofexor and/or
firsocostat 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 Annual Report
on Form 10-K for the year ended December 31, 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 www.gilead.com,
follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs
at 1-800-GILEAD-5 or 1-650-574-3000.
Contacts
Sung Lee, Investors
(650) 524-7792
Arran Attridge, Media
(650) 425-8975