April 11, 2019
Gilead Presents New Data in Nonalcoholic Steatohepatitis (NASH) at the International Liver Congress™ 2019
-- New Proof-of-Concept Data for Combination of Investigational FXR Agonist Cilofexor and ACC Inhibitor Firsocostat in 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
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.
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
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
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
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