Gilead Announces Phase 2 Results for GS-0976 in Nonalcoholic Steatohepatitis (NASH)
Gilead Sciences, Inc. (Nasdaq: GILD) today announced results from a Phase 2, randomized, placebo-controlled trial evaluating two doses of GS-0976, an oral, investigational inhibitor of Acetyl-CoA carboxylase (ACC), in patients with nonalcoholic steatohepatitis (NASH). The data demonstrate that the higher dose of GS-0976 (20 mg taken orally once daily) when administered for 12 weeks was associated with statistically significant reductions in hepatic steatosis (buildup of fat in the liver) and a noninvasive marker of fibrosis (TIMP-1) compared to placebo. These results are being presented during a late-breaking abstract session at The Liver Meeting ® 2017 in Washington, D.C. (Abstract #LB-9). Eighteen other abstracts on Gilead’s NASH and liver fibrosis pipeline were also presented at the meeting.
“In patients with advanced fibrosis, NASH may lead to severe complications including end-stage liver disease, hepatocellular carcinoma and the requirement for liver transplantation,” said Rohit Loomba, MD, MHSc, lead study author, Director of the NAFLD Research Center, Director of Hepatology, Professor of Medicine, and Vice Chief of the Division of Gastroenterology at University of California San Diego School of Medicine. “Unfortunately, there are no treatments available for these patients. In this first randomized, placebo-controlled, Phase 2 study of an ACC inhibitor in NASH, the data suggest that GS-0976 has the potential to play an important role in treating patients with this disease.”
ACC plays a role in one of several biologically relevant pathways associated with disease progression in NASH. ACC catalyzes the first step in hepatic de novo lipogenesis, the synthesis of fatty acids that contribute to hepatic steatosis and, subsequently, inflammation and liver fibrosis.
The study included 126 patients who were randomized to receive GS-0976 20 mg (n=49), GS-0976 5 mg (n=51), or placebo (n=26) once daily for 12 weeks. All patients in the study were diagnosed with NASH and liver fibrosis stages F1 through F3 based on biopsy, or by magnetic resonance elastography (MRE) and MRI proton density fat fraction (MRI-PDFF).
Patients receiving GS-0976 20 mg demonstrated significant decreases in liver fat content (measured by MRI-PDFF) compared to placebo after 12 weeks of treatment. Patients treated with GS-0976 20 mg also experienced a significant decrease in TIMP-1, a serum marker associated with liver fibrosis. Differences between GS-0976 5 mg and placebo were not statistically significant. Data for these efficacy endpoints are summarized in the table below.
Relative (%) Changes in Imaging, ALT and Serum Fibrosis Markers at Week 12*
|Endpoint (Week 12)||
20 mg vs.
5 mg vs.
|≥30% reduction in MRI-PDFF, % (n/N)||
|Liver stiffness by FibroScan||-11.1||-8.4||-3.1||0.212||0.364|
*Unless indicated, all data are median relative (%) changes from baseline.
In other measures, including liver stiffness by FibroScan, liver stiffness by MRE, serum ALT and PIII-NP, a serum marker of fibrogenesis, no statistically significant differences were observed between the treatment and placebo arms of the study.
At week 12, a median relative change in triglycerides (TG) from baseline of +11 percent, +13 percent and -4 percent was observed in patients receiving GS-0976 20 mg, GS-0976 5 mg and placebo, respectively. Asymptomatic Grade 3 or 4 TG elevations (>500 mg/dL) were observed in 16 patients receiving GS-0976 20 mg (n=7) or 5 mg (n=9); the primary factor associated with such elevations was a baseline TG level >250 mg/dL (p<0.001). The majority of patients with such elevations either responded to fibrate or fish oil therapy (n=4) or resolved without additional treatment or cessation of GS-0976 (n=7). GS-0976 was well-tolerated. Nausea, abdominal pain and diarrhea were the most common adverse events.
Other Gilead studies being presented at The Liver Meeting include preclinical data examining the combination of inhibitors of ACC and apoptosis signal-regulating kinase 1 (ASK1) in rodent models of NASH. These data suggest that the combination of agents resulted in greater anti-fibrotic and anti-steatotic efficacy than either agent alone (Abstract #425; named a Presidential Poster of Distinction). Gilead is currently conducting clinical studies evaluating combinations of the ASK1 inhibitor selonsertib, ACC inhibitor GS-0976 and the selective, non-steroidal Farnesoid X receptor (FXR) agonist GS-9674 in patients with NASH. Additional abstracts describe the accuracy of noninvasive markers to predict improvements in liver histology in response to treatment in a Phase 2 study of selonsertib, including reductions in fibrosis with MRE (Abstract #2104) and liver fat with MRI-PDFF (Abstract #2169). Phase 3 studies are ongoing with selonsertib in patients with advanced fibrosis due to NASH.
Gilead is also presenting multiple abstracts regarding primary sclerosing cholangitis (PSC), a progressive cholestatic liver disease with no approved therapies. These include presentations on the role of magnetic resonance cholangiopancreatography (MRCP) in PSC including a Presidential Plenary Oral Presentation (Abstract #140) describing a novel MRCP-based risk score for predicting PSC-related complications; an innovative technique for quantifying biliary tree volume in PSC (Abstract #292); prospective data describing the natural history of radiologic progression in PSC (Abstract #279; a Presidential Poster of Distinction); and the development and validation of a PSC-specific patient reported outcome (PRO) measure (Abstract #1351; a Presidential Poster of Distinction). These studies will enhance our understanding of PSC and aid in the development of novel therapies. Gilead is currently conducting a Phase 2 study of the FXR agonist GS-9674 in patients with PSC.
About Gilead’s Clinical Programs in NASH
NASH is a chronic liver disease associated with steatosis, or accumulation of fat within the liver, which can lead to inflammation, progressive fibrosis and cirrhosis. Gilead is advancing multiple novel investigational compounds for the treatment of NASH with advanced fibrosis. Gilead is currently planning or conducting Phase 2 and 3 clinical trials evaluating single-agent and combination therapy approaches against multiple core pathways associated with NASH – metabolic dysregulation, inflammation and fibrosis. 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.
Selonsertib, GS-9674 and GS-0976, alone and in combination, are investigational therapies and have not been determined to be safe or efficacious.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases. Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California.
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 GS-0976, selonsertib and GS-9674 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 GS-0976, selonsertib and/or GS-9674 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 June 30, 2017, 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.
Gilead Sciences, Inc.
Sung Lee, 650-524-7792 (Investors)
Nathan Kaiser, 650-522-1853 (Media)
For more than 50 years, Business Wire has been the global leader in press release distribution and regulatory disclosure.
Tilaa tiedotteet sähköpostiisi
Haluatko tietää asioista jo ennen kuin ne uutisoidaan? Kun tilaat tiedotteemme tältä julkaisijalta, saat ne sähköpostiisi yhtä aikaa suomalaisen median kanssa. Tilauksen voit halutessasi perua milloin tahansa.
Lue lisää julkaisijalta Business Wire
NTT Com Granted Microsoft's Gold Cloud Platform Status Globally17.1.2018 09:00 | Tiedote
NTT Communications Corporation (NTT Com), the ICT solutions and international communications business within the NTT Group (TOKYO:9432), is pleased to announce that it has been granted Microsoft Gold Cloud Platform status, the highest accreditation currently available, for its competency in delivering on quality, expertise and differentiated managed services in the cloud. This press release features multimedia. View the full release here: http://www.businesswire.com/news/home/20180116005911/en/ “Gold status is an important recognition of our competency in the cloud arena,” said Damian Skendrovic, CEO, NTT Com Managed Services. “With Microsoft Cloud Platform Competency we are helping enterprises to manage their hybrid cloud infrastructures, delivering on SaaS and PaaS solutions available in the Azure and Azure Stack marketplace that will enable our customers to optimize on performance and reach their business goals,” As part of its global strategy, NTT Com has been part of the early ado
Premas, IncellDx Ink India Distribution Agreement17.1.2018 08:01 | Tiedote
Premas Life Sciences Pvt., Ltd. and IncellDx, Inc. announced today they have signed an exclusive distribution agreement. The commercial partnership brings the power of cell by cell multiplex diagnostics for solid tumors carcinomas that can now be analyzed for molecular and protein biomarkers by flow cytometry. Included in the deal are: IncellDx's patented single-cell assays for quantifying PD-L1 on tumor cells and immune cell subtypes; patented single-cell assay for HPV E6, E7 mRNA detection in cervical samples; and, its incellPREP single-cell preparation kit for solid tissues including tumors. Researchers at AIIMS, New Delhi have completed a successful study utilizing IncellDx's next generation (3Dx) investigational molecular assay which quantifies E6, E7 mRNA overexpression in single cells simultaneously with the measurement of cell cycle and cell proliferation, the hallmark of progressive disease. Praveen Gupta, Managing Director of Premas Life Sciences commented: “India’s molecular
Ipsen and Exelixis announce phase 3 trial results of cabozantinib demonstrating significant overall survival benefit in patients with previously treated advanced hepatocellular carcinoma17.1.2018 01:05 | Tiedote
Regulatory News: Ipsen (Euronext:IPN; ADR:IPSEY) and Exelixis, Inc. (NASDAQ:EXEL) today announced detailed results of the pivotal phase 3 CELESTIAL trial in patients with previously treated advanced hepatocellular carcinoma (HCC), which will be presented in a late-breaking oral session at the 2018 ASCO-GI Symposium being held in San Francisco, January 18-20, 2018. In CELESTIAL, cabozantinib provided a statistically significant and clinically meaningful improvement versus placebo in overall survival (OS), the trial’s primary endpoint, at the planned second interim analysis (prespecified critical p value ≤ 0.021) for the population of second- and third-line patients enrolled in this study. Median OS was 10.2 months with cabozantinib versus 8.0 months with placebo (HR 0.76, 95 percent CI 0.63-0.92; p=0.0049). Median progression-free survival (PFS) was more than doubled, at 5.2 months with cabozantinib and 1.9 months with placebo (HR 0.44, 95 percent CI 0.36-0.52; p<0.0001). Objective resp
IFF to Release Fourth Quarter & Full Year 2017 Results February 1417.1.2018 00:15 | Tiedote
Regulatory News: International Flavors & Fragrances Inc. (NYSE:IFF) (Euronext Paris: IFF), a leading innovator of sensory experiences that move the world, announced that it will release its fourth quarter and full year 2017 earnings results following the market close on Wednesday, February 14, 2018. The management team will host a live webcast on Thursday, February 15, 2018 at 10:00 a.m. ET to discuss results and outlook with the investor community. Investors may access the live webcast and accompanying slide presentation on the Company's website at ir.iff.com. For those unable to listen to the live webcast, a recorded version will be made available for replay. Meet IFF International Flavors & Fragrances Inc. (NYSE:IFF) (Euronext Paris: IFF) is a leading innovator of sensorial experiences that move the world. At the heart of our company, we are fueled by a sense of discovery, constantly asking “what if?”. That passion for exploration drives us to co-create unique products that consumer
President Clinton to Address Healthcare Leaders Focused on Eliminating Preventable Deaths in Hospitals at the 6th Annual World Patient Safety, Science & Technology Summit16.1.2018 22:17 | Tiedote
For the 6th year in a row, President Bill Clinton, the Founder of the Clinton Foundation and 42nd President of the United States, will deliver keynote remarks at the 6th Annual World Patient Safety, Science and Technology Summit held in London, England, February 23-25, 2018. President Clinton, who serves as Honorary Chair of the Patient Safety Movement Foundation’s Regional Network Chairs, joins an acclaimed group of global leaders, government representatives, healthcare and hospital CEOs, medical experts and patient advocates who will gather for the first time in London to confront preventable hospital deaths around the world. This press release features multimedia. View the full release here: http://www.businesswire.com/news/home/20180116006614/en/ President Bill Clinton, the Founder of the Clinton Foundation and 42nd President of the United States, to speak at the 6th Annual World Patient Safety, Science & Technology Summit in London, England (Photo: Business Wire) “We are thrilled
Disaronno: The Mixing Star Makes a Step Change and Looks to Innovation16.1.2018 19:06 | Tiedote
After 10 years of competitions involving bartenders from different countries who were challenged to showcase the mixability of Disaronno, Disaronno’s contest The Mixing Star has changed direction. Convinced that trends today move on channels other than a performance in front of a jury, Disaronno, the most consumed Italian liqueur in the world and the brand embodying the coolest soul of Made in Italy, has transformed The Mixing Star to Innovation Hunter, a social media based "exploration" with a mission: identifying innovative trends in mixology and movers and shakers in the field, in the UK and around the world, filming and sharing them with the community of bartending experts. In London, Milan and Amsterdam Disaronno has selected a few bartenders who are revolutionizing the field. The ways in which they express innovation have been collected in a set of stylish short movies specially made by Disaronno. The protagonists are available on The Mixing Star Facebook page and YouTube channel
Uutishuoneessa voit lukea tiedotteitamme ja muuta julkaisemaamme materiaalia. Löydät sieltä niin yhteyshenkilöidemme tiedot kuin vapaasti julkaistavissa olevia kuvia ja videoita. Uutishuoneessa voit nähdä myös sosiaalisen median sisältöjä. Kaikki STT Infossa julkaistu materiaali on vapaasti median käytettävissä.Tutustu uutishuoneeseemme