13 November 2018 - - US-based biopharmaceutical company Gilead Sciences, Inc. (NASDAQ: GILD) has presented new data from the company's clinical development programme for advanced fibrosis due to nonalcoholic steatohepatitis, the company said.

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 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% in hepatic fat measured by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) was observed in 38.9% of patients treated with GS-9674 100 mg (p=0.011 vs placebo), 14% treated with GS-9674 30 mg (p=0.87), and 12.5% 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% of patients in the GS-9674 100 mg arm compared to four % 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 (2%), five patients treated with GS-9674 30 mg (9%), and two patients with placebo (7%).

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 inhibitor GS-0976 alone or in combination, in patients with advanced fibrosis due to NASH.

This randomised, double-blind 52-week study will assess improvement in fibrosis without worsening of NASH, adverse events and laboratory abnormalities in approximately 350 patients.

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 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 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% of patients while reducing the frequency of indeterminate results to as low as 13%.

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 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 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 US Food and Drug Administration or any other regulatory authority. Their safety and efficacy have not been established.

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 or cirrhosis, 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 or cirrhosis is ongoing. GS-9674 and GS-0976 are currently in Phase 2 studies in NASH.

Gilead Sciences is a 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.