Gilead Presents Data on Multiple Investigational Regimens for the Treatment of Patients With Nonalcoholic Steatohepatitis (NASH) and Advanced Fibrosis at The International Liver Congress™ 2018
Gilead Sciences, Inc. (Nasdaq: GILD) today presented data from a proof-of-concept study of investigational combination therapies for patients with advanced fibrosis due to nonalcoholic steatohepatitis (NASH), combining the apoptosis signal-regulating kinase 1 (ASK1) inhibitor selonsertib with either the Acetyl-CoA carboxylase (ACC) inhibitor GS-0976 or the selective, non-steroidal Farnesoid X receptor (FXR) agonist GS-9674. The data were presented at The International Liver Congress™ 2018 in Paris.
More than 25 additional Gilead abstracts on NASH and other fibrotic liver diseases are also being presented, including data from predictive modeling studies using noninvasive tests for the diagnosis and monitoring of NASH that aim to reduce the need for liver biopsy.
“Gilead is focused on addressing the greatest unmet need in NASH, which is in patients with advanced fibrosis. Reflective of this unmet need, the STELLAR-3 and STELLAR-4 studies of selonsertib in patients with F3 and F4 fibrosis have completed enrollment ahead of schedule. We expect data from these Phase 3 studies in the first half of 2019,” said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer at Gilead. “We are now exploring combination therapy approaches with compounds with distinct and potentially complementary mechanisms of action. The initial data presented today are important advances toward our goal of improving outcomes for patients with advanced fibrosis due to NASH.”
Investigational Combination Therapies in Patients with NASH
The proof-of-concept study (Oral #105) included 70 patients treated with either selonsertib 18 mg plus GS-0976 20 mg (n=20), selonsertib 18 mg plus GS-9674 30 mg (n=20), or each monotherapy (n=10 per group) once daily for 12 weeks. All patients in the study were diagnosed with NASH and liver fibrosis stages F2 to F3 based on biopsy, or by magnetic resonance elastography (MRE) and MRI proton density fat fraction (MRI-PDFF). The greatest changes observed after 12 weeks of treatment in the study were decreases in liver fat content (measured by MRI-PDFF), which occurred in regimens containing GS-0976. Improvements in liver biochemistry and/or markers of fibrosis were also observed across both combination arms of the study compared to baseline. In patients treated with selonsertib plus GS-0976, kinetic labeling revealed the largest reduction in the fractional synthesis rate of lumican, a marker of fibrogenesis. Similar rates of adverse events were observed between patients treated with single-agent and combination therapies. No patient discontinued treatment prematurely.
“These encouraging results suggest that combination therapy with selonsertib and either GS-0976 or GS-9674 warrants further exploration in longer-term studies in patients with NASH and F3 and F4 fibrosis,” said Stephen Harrison, MD, presenting author and Visiting Professor of Hepatology at the Radcliffe Department of Medicine, University of Oxford, UK. “Patients with advanced fibrosis due to NASH urgently need effective therapeutic options because they may face more serious health risks, including development of complications of end-stage liver disease, liver cancer and the need for liver transplantation. Combination therapy may be a way forward to achieving greater benefit for this patient population.”
Gilead also presented data from a pre-clinical study of another combination treatment approach for NASH, evaluating GS-9674 and GS-0976 together and as single-agents in rodent models of NASH and liver fibrosis (Poster #077). The data indicate that combining agents had greater anti-fibrotic and anti-steatotic effects and led to greater improvements in liver biochemistry and fibrosis markers, compared with either agent alone.
Based on these promising pre-clinical results and data from the proof-of-concept clinical study, Gilead has initiated a larger Phase 2b study of combination treatment with selonsertib, and/or GS-0976, and/or GS-9674 in patients with advanced fibrosis due to NASH.
Data from Noninvasive Tests Help Predict Histological Severity and Clinical Outcomes in Patients with NASH
Currently, the diagnosis and monitoring of NASH requires liver biopsy, an invasive and costly procedure with the potential for serious complications. At the meeting, Gilead presented results from two studies utilizing machine learning techniques which suggest that noninvasive tests perform as effectively as liver biopsy for predicting clinical outcomes in patients with advanced fibrosis due to NASH. Both studies utilized data from two previous Phase 2b trials of simtuzumab that involved 477 NASH patients with F3-F4 fibrosis. While simtuzumab was ineffective, data from these trials have revealed important insights into the natural history of disease progression and the potential utility of noninvasive fibrosis markers.
One study (Poster #466) showed that models using noninvasive testing data can predict the risk of clinical disease progression in patients with advanced fibrosis due to NASH. Another study (Oral #178) identified models that can predict which patients are most likely to experience spontaneous fibrosis improvement. Both studies incorporated noninvasive tests such as Enhanced Liver Fibrosis (ELF) score, FIB-4 and NAFLD fibrosis score.
Additional presentations at The International Liver Congress™ describe the accuracy of other noninvasive markers, including proteomics (Poster #432), serum bile acids (Poster #422), micro-RNAs (Poster #463), and the stool microbiome (Poster #004) to predict liver histology and/or its change over time. These novel approaches will be evaluated in future Gilead studies.
About Gilead’s Clinical Programs in NASH
NASH is a chronic and progressive liver disease characterized by the accumulation of fat in the liver, as well as inflammation, which can lead to liver damage and fibrosis. Gilead is advancing multiple novel investigational compounds for the treatment of advanced fibrosis due to NASH.
Gilead is currently planning or conducting Phase 2 and 3 clinical trials evaluating single-agent and combination therapy approaches against multiple biologically relevant pathways associated with NASH – metabolic dysregulation, inflammation and fibrosis. Compounds in development include:
- Selonsertib (formerly GS-4997) – A small-molecule inhibitor of apoptosis signal-regulating kinase 1 (ASK1), which promotes inflammation, apoptosis and fibrosis in settings of increased oxidative stress, which is characteristic of NASH and associated with its pathogenesis.
- GS-9674 – A selective, non-steroidal agonist of the Farnesoid X receptor (FXR), a nuclear hormone receptor that is highly expressed in the gastrointestinal tract and liver. FXR is the primary regulator of bile acid synthesis and plays important roles in glucose and lipid metabolism.
- GS-0976 – A small-molecule inhibitor of Acetyl-CoA carboxylase (ACC), an enzyme that is involved in de novo lipogenesis, which is the synthesis of lipids, including mediators of inflammation and fibrosis. ACC also upregulates the burning of fat in the liver through beta oxidation.
Selonsertib, GS-9674 and GS-0976, alone and in combination, are investigational therapies and their efficacy and safety have not been determined.
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 35 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 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 Gilead’s Annual Report on Form 10-K for the year ended December 31, 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
Arran Attridge, 650-425-8975
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 ensimmäisten joukossa? Kun tilaat mediatiedotteemme, saat ne sähköpostiisi välittömästi julkaisuhetkellä. Tilauksen voit halutessasi perua milloin tahansa.
Lue lisää julkaisijalta Business Wire
myPOS Presented with Best POS Innovation Award by the Merchant Payment Ecosystem21.2.2019 17:57:00 | Tiedote
myPOS, one of the fastest growing European payment providers was handed the Best POS Innovation/POS Software Payment Applications award for 2019 by the Merchant Payment Ecosystem (MPE) at a Gala Dinner ceremony in Berlin last night. Being known for offering instant settlement and no-monthly-fees model to SMEs across Europe, myPOS provides a range of innovative features on its payment devices, some of which include Tipping, Payment Request, Top-up and GiftCards. In addition, myPOS merchants are entitled to a whole range of subscription-free, value-added services such as Virtual MO/TO, PayLinks and PayButtons, Checkout module with the most popular shopping carts and more. myPOS clients are also given the opportunity to manage their funds with a free online account and a unique banking platform. The company got nominated in two categories: Best POS Innovation and Best Acquirer of the year, but ultimately won the Best POS Innovation award. "We accept this award with gratitude and appreciat
New Release Crea Records: "ABBA We Love You Forever"21.2.2019 17:44:00 | Tiedote
Not many people on this earth can say that they have never heard of ABBA. In addition to the wonderful voices of Agnetha Fältskog and Anni-Fried Lyngstad, the musicians, Björn Ulvaeus and Benny Andersson have written the most wonderful songs, not only composed with charm and elegance, but also so breathtakingly beautiful and unforgettable that they will always resonate. For the Danish singer, BILLBOARD Hot 100 artist, composer and lyricist, Lecia Jonsson, ABBA has been much more than an inspiration. Lecia shared the same melodic universe as ABBA, making her mark with many records as part of duo LECIA & LUCIENNE. Later, as part of another duo, LABAN, Lecia entered BILLBOARD HOT 100 in the United States, had releases in 48 countries worldwide, and sold more than 1.5 million albums. Lecia’s identity is formed by her pure voice and her great sense for writing unique songs filled with a great melodic substance. If anyone should write a song to honour ABBA’s music, Lecia is definitely the pe
Ultivue Expands Global Presence with Opening of European Subsidiary, Ultivue EMEA Srl21.2.2019 17:30:00 | Tiedote
Ultivue, a developer of tissue biomarker identification and quantification assays for pathology and translational research labs, today announced that it has expanded its commercial footprint with a wholly-owned European subsidiary and appointed Luigi Pirovano as General Manager. Mr. Pirovano is an international executive with significant experience managing European Diagnostics and Life Science operations and will be responsible for managing the new subsidiary, Ultivue EMEA Srl, located in Milan, Italy. “The establishment of a European subsidiary provides an excellent structure to support Ultivue’s expanded commercial activities across Europe and engage deeply and efficiently with the biomedical community,” said Philippe Mourere, Ultivue’s Senior Vice President of Commercial Operations. “Ultivue will capitalize on Luigi’s demonstrated success leading both Life Science and Diagnostics activities to continue driving strong execution of its business plan.” Luigi Pirovano has more than 30
NTT DATA Launches Advanced 3D Digital Map Package for 5G Network Planning21.2.2019 17:00:00 | Tiedote
NTT DATA (TOKYO:9613), a leading IT services provider, announced today its launch of “AW3D Telecom for 5G,” an advanced 3D digital map package that leverages high-quality satellite imagery for the planning of fifth-generation (5G) wireless networks, effective immediately. AW3D for 5G is expected to be used by telecom carriers, network vendors and IoT companies engaged in businesses involving 5G networks. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20190221005320/en/ Images of AW3D Telecom for 5G (Graphic: Business Wire) Commercial 5G services via fixed wireless access networks launched in the USA in 2018 and will begin operating in Japan, South Korea, the UK and Australia in 2019. Accurate 3D models are crucial for designing 5G networks, which use millimeter-spectrum waves that are highly sensitive to interference from natural and manmade objects. Buildings, trees, bridges, flyover roads, etc. need to be expressed precisely
Seoul Semiconductor Made Global Distributor Stop Selling Everlight Product in Japan21.2.2019 17:00:00 | Tiedote
Seoul Semiconductor Co., Ltd. (KOSDAQ 046890) (“Seoul”), a leading global innovator of LED products and technology, announced that it has concluded a patent infringement lawsuit seeking an injunction on the sales of certain LED product sold by Mouser Electronics (“Mouser”). The accused LED product was manufactured by Everlight Electronics Co., Ltd. (“Everlight”). This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20190221005040/en/ Seoul Semiconductor's Headquarters in Korea (Photo: Business Wire) In February 2018, Seoul filed a patent infringement lawsuit with the Tokyo District Court, accusing the LED product manufactured by Everlight and sold by Mouser of infringing an LED patent of Seoul’s affiliate. Mouser agreed not to export the accused Everlight LED product in Japan, and Seoul therefore agreed to withdraw the lawsuit. The patented technology involved in this litigation serves to efficiently extract light emitted from the i
Universal Laser Systems Maximizes Material Compatibility in New ULTRA 9 Platform21.2.2019 16:05:00 | Tiedote
With the increasing use of advanced materials in industrial applications from aerospace to medical devices comes a growing need for innovation in material conversion technology. Developments in laser processing aim to overcome the limitations of existing technology and push the boundaries of how materials can be used. To this end, Universal Laser Systems has released a platform with unprecedented material processing capabilities. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20190221005340/en/ ULTRA 9 laser platform (Photo: Business Wire) The new ULTRA 9 Platform is designed to perform laser cutting, laser ablation, and laser surface modification. When configured with patented MultiWave Hybrid™ technology, it can combine the laser energy of up to three wavelengths – 9.3 µm (CO2), 10.6 µm (CO2), and 1.06 µm (fiber) – by independently controlling each spectral component of the beam. The user is able to select the ideal waveleng
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