Gilead Sciences, Inc. (Nasdaq: GILD) today announced new data from the companys clinical development program for advanced fibrosis due to nonalcoholic steatohepatitis (NASH). Data presented support the ongoing development of the companys 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 patients.
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.
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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 established.
About Gileads 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 NASH.
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 companys website at www.gilead.com.
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 Gileads 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 Gileads 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 companys 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
Gilead Sciences, Inc.
Sung Lee, 650-524-7792