Gilead Data On Phase 3 STELLAR-4 Study of Selonsertib in Compensated Cirrhosis (F4) Due to Nonalcoholic Steatohepatitis (NASH)

Media
A fatty liver drug from Gilead Sciences posts negative results in late-stage clinical trial
By Adam Feuerstein @adamfeuerstein

February 11, 2019

Gilead Sciences said Monday that its experimental drug, called selonsertib, failed to improve liver scarring compared to a placebo in a Phase 3 clinical trial. The study enrolled nearly 900 patients with compensated cirrhosis, an advanced form of NASH at higher risk for liver-related death.

Read it here...

Press release

Gilead Announces Topline Data From Phase 3 STELLAR-4 Study of Selonsertib in Compensated Cirrhosis (F4) Due to Nonalcoholic Steatohepatitis (NASH)
FOSTER CITY, Calif.--(BUSINESS WIRE)--Gilead Sciences, Inc. (Nasdaq: GILD) today announced that STELLAR-4, a Phase 3, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of selonsertib, an investigational, once-daily, oral inhibitor of apoptosis signal-regulating kinase 1 (ASK1), in patients with compensated cirrhosis (F4) due to nonalcoholic steatohepatitis (NASH), did not meet the pre-specified week 48 primary endpoint of a ≥ 1-stage histologic improvement in fibrosis without worsening of NASH.

In the study of 877 enrolled patients who received study drug, 14.4 percent of patients treated with selonsertib 18 mg (p=0.56 vs. placebo) and 12.5 percent of patients treated with selonsertib 6 mg (p=1.00) achieved a ≥ 1-stage improvement in fibrosis according to the NASH Clinical Research Network (CRN) classification without worsening of NASH after 48 weeks of treatment, compared with 12.8 percent of patients who received placebo. Selonsertib was generally well-tolerated and safety results were consistent with prior studies.

“While we are disappointed that the STELLAR-4 study did not achieve its primary endpoint, we remain committed to advancing therapies for patients with advanced fibrosis due to NASH, where there is a significant unmet need for effective and well-tolerated treatments. Gilead has a long-term commitment and proven track record of addressing significant challenges in the field of liver diseases. Data from this large study of patients with compensated cirrhosis due to NASH, including the extensive set of biomarkers collected, will further advance our understanding of the disease and inform our broader NASH development programs,” said John McHutchison, AO, MD, Chief Scientific Officer, Head of Research and Development, Gilead. “We are grateful to the patients and investigators who participated in the STELLAR-4 study, and we now await the upcoming results from the Phase 3 STELLAR-3 trial of selonsertib in patients with bridging fibrosis (F3) due to NASH and the Phase 2 ATLAS combination trial of selonsertib, cilofexor (GS-9674) and firsocostat (GS-0976) in patients with advanced fibrosis due to NASH later this year.”

Further in-depth analysis of the findings is ongoing and the data will be submitted to an upcoming scientific conference. Gilead will work with the Data Monitoring Committee and investigators to conclude the STELLAR-4 study in a manner consistent with the best interests of each patient.

Selonsertib, cilofexor and firsocostat, alone or in combination, are investigational compounds and are not approved by the U.S. Food & Drug Administration (FDA) or any other regulatory authority. Safety and efficacy have not been established for these agents.

About Selonsertib and the STELLAR-4 Study
Selonsertib is an investigational small molecule inhibitor of ASK1, a protein that promotes inflammation, apoptosis (cell death) and fibrosis in settings of oxidative stress. Oxidative stress can be increased in many pathological conditions including liver diseases such as NASH.

The STELLAR-4 study is a Phase 3, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of selonsertib in patients with compensated cirrhosis (F4) due to NASH. Eligible adults ages 18 to 70 years were randomized and received selonsertib 18 mg (n=354), selonsertib 6 mg (n=351) or placebo (n=172) for up to 240 weeks. Either selonsertib or placebo is being administered orally once daily. The primary endpoints of the study are a composite of the proportion of patients who achieve a ≥ 1-stage improvement in fibrosis according to the NASH CRN classification without worsening of NASH at week 48 and event-free survival at week 240 as assessed by time to the first clinical event. Further information about the clinical study can be found at www.clinicaltrials.gov.

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 with advanced fibrosis, including bridging fibrosis (F3) or compensated cirrhosis (F4), 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 Phase 2 trial evaluating combinations of selonsertib, cilofexor and firsocostat in advanced fibrosis (F3 and F4) due to 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 company’s website at www.gilead.com.

At JPM, the NASH flood gates start to crack

J.P. Morgan Healthcare Conference in San Francisco

At JPM, the NASH flood gates start to crack 
Jacob Bell

Four companies are within striking distance of filing NASH drugs for approval, but the competitive landscape is more nuanced than simply crossing the finish line first...

While JPM didn't bring data updates for the later-stage NASH pipeline, drugmakers did give more color on their mindset heading into such a pivotal year....

John McHutchison, Gilead's head of R&D, told investors at JPM he anticipates "waves of approval," with the first being highly potent treatments for patients who have more advanced fibrosis, and then subsequent waves that work on less severe NASH and have better safety profiles.....
Read the article:
https://www.biopharmadive.com/news/nash-2019-jpm-readouts-deals-market-competition/545772/

Articles available on this blog: Nonalcoholic Steatohepatitis (NASH)
Non-alcoholic Fatty Liver Disease (NAFLD)
Jan 11, 2019 - NASH update: 6 recent reports on treatment development 
Jan 9, 2019 - Gilead Sciences and Yuhan Corporation Announce Collaboration and License Agreement to Develop Novel Investigational Treatments for Advanced Fibrosis Due to Nonalcoholic Steatohepatitis 
After The Liver Meeting 2018 Summary: Viral Hepatitis & Fatty Liver Disease 

Gilead Presents Data From Nonalcoholic Steatohepatitis (NASH) Development Program for Advanced Fibrosis at The Liver Meeting® 2018
All current NASH & NAFLD blog posts:
Watch videos, or review research in this current collection of articles

NASH update: 6 recent reports on treatment development

Healio - Hepatology - Steatohepatitis/Metabolic Liver Disease 

NASH update: 6 recent reports on treatment development

Researchers continue efforts to study and develop safe and effective therapeutics to treat nonalcoholic fatty liver disease and its progressive form, nonalcoholic steatohepatitis, including several collaborative efforts between clinical development companies and societies.

Healio Gastroenterology and Liver Disease presents the following reports on recent NASH studies including data on a newly formed “NASH Roundtable,” positive results from recent clinical trials, and a new LiverMultiScan tool for identifying NASH....

Read more: https://www.healio.com/hepatology/steatohepatitis-metabolic-liver-disease/news/online/%7B8db09cf7-1eb0-4103-8b70-efab71f1d962%7D/nash-update-6-recent-reports-on-treatment-development

Gilead and Yuhan co-develop novel therapeutic candidates for Nonalcoholic Steatohepatitis (NASH)

Gilead Sciences and Yuhan Corporation Announce Collaboration and License Agreement to Develop Novel Investigational Treatments for Advanced Fibrosis Due to Nonalcoholic Steatohepatitis
Gilead Sciences and Yuhan Corporation Announce Collaboration and License Agreement to Develop Novel Investigational Treatments for Advanced Fibrosis Due to Nonalcoholic Steatohepatitis

FOSTER CITY, Calif. & SEOUL, Korea--(BUSINESS WIRE)--Jan. 6, 2019-- Gilead Sciences, Inc. (NASDAQ: GILD) and Yuhan Corporation (000100.KS; Yuhan) today announced that the companies have entered into a licensing and collaboration agreement to co-develop novel therapeutic candidates for the treatment of patients with advanced fibrosis due to nonalcoholic steatohepatitis (NASH).

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20190106005116/en/

Under the agreement, Gilead will acquire global rights to develop and commercialize novel small molecules against two undisclosed targets in all countries, with the exception of the Republic of Korea where Yuhan will retain certain commercialization rights. Yuhan and Gilead will jointly conduct preclinical research, and Gilead will be responsible for global clinical development. Gilead will also be responsible for commercialization worldwide, outside of Yuhan’s rights in the Republic of Korea. In connection with this agreement, Yuhan will receive an upfront payment of $15 million and is eligible to receive up to an additional $770 million in potential milestone payments upon achievement of certain development and commercial milestones, as well as royalties on future net sales. This agreement builds on the companies’ existing commercial collaboration to support the promotion of Gilead’s medicines in the Republic of Korea.

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 due to NASH, defined as bridging fibrosis (F3) or cirrhosis (F4), may face serious consequences, including end-stage liver disease, liver cancer and the need for liver transplantation, and are at a significantly higher risk of liver-related mortality. Currently, patients living with NASH have limited treatment options.

“This collaboration builds on our long-term partnership with Yuhan, with a new focus on the investigation of novel approaches to treat patients with advanced fibrosis due to NASH that complement our ongoing research programs,” said John McHutchison, MD, AO, Chief Scientific Officer and Head of Research and Development, Gilead Sciences. “We look forward to working with the Yuhan team to advance our work in this area where there is a significant unmet need for patients.”

“I am very pleased by this collaboration, which significantly expands and deepens our longstanding, trusted partnership with Gilead. We are confident that Gilead’s expertise in liver disease will accelerate the development of our novel agents. As a company, we are committed to investigating new therapeutics to improve the lives of patients with NASH,” said Mr. Jung Hee Lee, President and CEO of Yuhan.

The $35 billion race to cure a silent killer that affects 30 million Americans

Modern Medicine 

Sun, December 30, 2018 7:39 AM 

In the U.S. 30 million Americans suffer from a form of fatty liver disease that turns into a form of liver cirrhosis that leads to death unless a patient can receive a liver transplant. Now drug companies are spending billions to help find a cure.

The $35 billion race to cure a silent killer that affects 30 million Americans

Lori Ioannou

The race is on in the pharmaceutical industry to develop drugs to treat a form of fatty liver disease called nonalcoholic steatohepatitis, also known as NASH.

Industry experts estimate the global market for these new drugs is $35 billion.

The U.S. is spending $5 billion annually in health-care costs related to the disease, which include chemotherapy, transplants, tests and hospitalizations, reports the Center for Disease Analysis.

The National Institutes of Health estimates as many as 12 percent of U.S. adults have this disease, or 30 million people.

Read More: https://www.cnbc.com/2018/12/21/the-35-billion-race-for-a-cure-for-a-liver-disease-that-affects-millions.html

HighTide Receives Fast Track Designation for new drug to treat NASH

[Rockville, Maryland, Nov. 27, 2018] — HighTide Therapeutics Inc., a clinical-stage biopharmaceutical company, announced that the U.S. FDA has granted Fast Track Designation to its investigational new drug, HTD1801, for the treatment of patients with nonalcoholic steatohepatitis (NASH).

Liping Liu, PhD, Chief Executive Officer of HighTide, commented, “NASH represents a rapidly developing field with potential therapeutic options in the pipeline, yet none have made it to the market. At the recent AASLD Liver Meeting, experts in the field generally agreed that modest clinical responses to date are likely to be improved by thoughtful combination approaches. HTD1801, a multifunctional oral therapeutic, was designed to address the complex nature of NASH, especially for patients with comorbid diabetes and/or dyslipidemia. We are pleased by the FDA’s decision and look forward to bringing this much needed solution to millions of patients suffering from this disease.”

“This represents another step forward in our development of HTD1801 for the treatment of liver diseases with no currently approved therapies. We are proceeding with parallel clinical development of HTD1801 for NASH as well as primary sclerosing cholangitis (PSC) for which HTD1801 already received Orphan Drug Designation and Fast Track Designation,” said Janice Soreth, M.D., Chief Strategy and Regulatory Officer of HighTide, former Associate Commissioner for Special Medical Programs at the FDA.

FDA’s Fast Track program is designed to facilitate the development and expedite the review of new drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs. An investigational drug that receives Fast Track Designation is eligible for more frequent communications between the FDA and the company relating to the development plan and clinical trial design, and may be eligible for priority review if certain criteria are met.

HighTide completed a first in human study of HTD1801 in healthy volunteers. A multi-center Phase 2 trial in adult patients with NASH is scheduled to enroll soon in the United States. A multi-center Phase 2 trial in adult patients with PSC is currently ongoing in the United States.

About HighTide Therapeutics and HTD1801
HighTide Therapeutics Inc., founded in 2011, is dedicated to the discovery and development of innovative therapeutics for people suffering from chronic liver diseases, gastrointestinal diseases and metabolic disorders with large and unsatisfied market needs.

HTD1801 is a new molecular entity being developed for the treatment of PSC and NASH.

About Nonalcoholic Steatohepatitis
Nonalcoholic steatohepatitis (NASH), a form of nonalcoholic fatty liver disease (NAFLD), is a chronic, complex liver disease characterized by hepatitis – inflammation of the liver – and liver cell damage, which can lead to fibrosis of the liver. NASH can lead to cirrhosis and liver cancer. Prevalence of NASH is on the rise and it may soon surpass hepatitis C as a cause for liver transplant. Currently, there are no approved therapies for NASH.

Gilead Presents Data From Nonalcoholic Steatohepatitis (NASH) Development Program for Advanced Fibrosis at The Liver Meeting® 2018

Meeting Coverage @ Healio

Nov 27, 2018

VIDEO: Gilead reports phase 2 safety, efficacy of GS-9674 for NASH

SAN FRANCISCO — In this exclusive video perspective from The Liver Meeting 2018, Rob Myers, MD, senior director of the liver diseases therapeutic area at Gilead…

View all updates on this blog (LINK), recommended coverage elsewhere (LINK). 

Gilead Press Release

November 09, 2018

Gilead Presents Data From Nonalcoholic Steatohepatitis (NASH) Development Program for Advanced Fibrosis at The Liver Meeting® 2018

-- Phase 2 Data Presented on Investigational FXR Agonist GS-9674 in NASH --
-- Enrollment Complete in Phase 2 ATLAS Combination Trial of Three Investigational Therapies Targeting Distinct Mechanisms of the Disease --

SAN FRANCISCO--(BUSINESS WIRE)--Nov. 9, 2018-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced new data from the company’s clinical development program for advanced fibrosis due to nonalcoholic steatohepatitis (NASH). 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 (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.”

Noninvasive Tests
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 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 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.
http://investors.gilead.com/phoenix.zhtml?c=69964&p=irol-newsArticle&ID=2376502

The Liver Meeting: Gilead making gains in NASH, PSC programs

New data from two mid-stage studies of Gilead Sciences Inc.'s farnesoid X receptor agonist (FXR) reported during the American Association for the Study of Liver Diseases meeting showcased the company's ongoing efforts to establish new strengths beyond viral hepatitis C, where time and competition have eroded its dominance. Though still active on the next frontier of the hepatitis battle, HBV, most of the company's liver disease pipeline today is focused on nonalcoholic steatohepatitis (NASH), primary sclerosing cholangitis (PSC), and primary biliary cirrhosis (PBC).

Liver Meeting® 2018 - Conatus Pharmaceuticals Announces Presentations and Posters

Liver Meeting® - Conatus Pharmaceuticals Announces Presentations and Posters

SAN DIEGO, Nov. 08, 2018 (GLOBE NEWSWIRE) -- Conatus Pharmaceuticals Inc. (NASDAQ: CNAT) announced today the schedule of upcoming oral presentations and posters addressing clinical and preclinical results with the company’s pan-caspase inhibitor emricasan, or addressing preclinical results with the company’s pan-caspase inhibitor IDN-7314, at The Liver Meeting®, the annual meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco November 9-13, 2018.

Poster #1226, “Multicenter, double-blind, randomized trial of emricasan in subjects post liver transplantation (LT) with recurrent hepatitis C virus (HCV) and liver fibrosis or cirrhosis despite achieving sustained virologic response (SVR),” will be displayed by Catherine Frenette, M.D., (Scripps Clinic, La Jolla, CA) in the Liver Transplantation: Viral Hepatitis section on Saturday, November 10, from 2:00 p.m. to 7:30 p.m. PT, in the Moscone Center Poster Hall – Hall C.

Presentation #251A, highlighting selected content from poster #1226, will be delivered by K. Rajinder Reddy, M.D., (University of Pennsylvania Medical Center, Philadelphia, PA) in the Parallel 37: Liver Transplantation: Alcohol and Hepatitis C session on Monday, November 12, at 3:15 p.m. PT, in the Moscone Center Room 153/155.

Presentation #25, “Intestinal dysbiosis augments liver disease progression via NLRP3 in a murine model of primary sclerosing cholangitis,” will be delivered by Kai M. Schneider (Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany) in the Presidential Plenary Session on Translational Science and Genomics on Tuesday, November 13, 9:00 a.m. PT., in the Moscone Center General Session – Hall D.

Poster #1344, “Molecular mechanisms underlying the effects of emricasan in portal hypertension and chronic liver disease: the hepato-sinusoidal cross-talk matters,” will be displayed by Jordi Gracia-Sancho, Ph.D., (Idibaps Biomedical Research Institute, Ciberehd, Barcelona, Spain; Hepatology, Inselspital, Bern, Switzerland; and Barcelona Liver Services) in the Portal Hypertension and Other Complications of Cirrhosis: Experimental section on Saturday, November 10, from 2:00 p.m. to 7:30 p.m. PT, in the Moscone Center Poster Hall – Hall C.

“With three ongoing ENCORE Phase 2b clinical trials evaluating emricasan in patients with nonalcoholic steatohepatitis (NASH), all with top-line results expected over the next nine months, we are encouraged by the preclinical and clinical data being featured at the AASLD meeting demonstrating the activity and effects of pan-caspase inhibitors,” said Conatus co-founder, President and Chief Executive Officer Steven J. Mento, Ph.D. “We thank our principal investigators and our scientific collaborators for their continued efforts to better understand and apply the multiple mechanistic effects of caspase inhibitors on liver structure and function, driving their disease-modifying potential. We are pleased with the opportunity to share their latest findings at the AASLD meeting, and we look forward to sharing results from the ENCORE trials.”
www.conatuspharma.com.

Liver Meeting® 2018- Exalenz to Present Positive Clinical Data for Breath ID® in NASH cirrhosis patients

Exalenz to Present Positive Clinical Data for the Breath ID® 13C-Methacetin Breath Test System at the Liver Meeting® 2018

MODI’IN, Israel and MANASQUAN, N.J., Nov. 05, 2018 (GLOBE NEWSWIRE) -- Exalenz Bioscience Ltd. (TASE: EXEN), a leader in developing and marketing non-invasive medical devices for diagnosing and monitoring a range of gastrointestinal and liver diseases, today announced that the Company will present positive data from a Phase 2 trial, conducted by Galectin Therapeutics in NASH cirrhosis patients (ie the NASH-CX trial), utilizing its BreathID® 13C-Methacetin Breath Test (MBT) System in patients with compensated non-alcoholic steatohepatitis (NASH).

The poster presentation is titled “The Noninvasive Point of Care MBT Accurately Predicts Decompensation Events Better Than MELD in Compensated (MELD <15) Nash Cirrhotics” (#1337) will be presented at the Liver Meeting® 2018 on November 10 at 2:00 PM PT / 5:00 PM ET. The Liver Meeting, the annual meeting of the American Association for the Study of Liver Diseases (AASLD), is being held November 9 - 13, 2018 in San Francisco. The lead author is Naga Chalasani, MD, Associate Dean for Clinical Research and a Professor of Medicine at the Indiana University School of Medicine.

“Results of this study indicate that the MBT has the potential to predict liver decompensation in patients with compensated NASH cirrhosis, which may enable earlier intervention and improved management of these patients,” said Raffi Werner, Chief Executive Officer of Exalenz Bioscience. “We believe that these results add to the growing body of data supporting the MBT as an important alternative to more invasive detection methods and support our strategy to advance this innovative test to the market, potentially launching the product in 2020.”

About MBT
MBT is a simple, noninvasive Point of Care breath-based test in which a patient drinks a half glass of a tasteless solution that is metabolized exclusively in the liver. The patient’s exhaled breath is automatically collected and assayed with the BreathID® system to measure the amount of a specific breakdown product of the solution, which reflects the rate of liver metabolism.

In addition to evaluating MBT to monitor NASH patients, it is also being developed to detect CSPH in the advanced NASH patient population, as well as in monitoring patients with confirmed diagnoses of acute liver failure (ALF). The ability to monitor patients with a simple, noninvasive test has the potential to radically improve the management and outcomes of patients with an array of liver diseases.

About NASH

More than 8 million people in the United States and Europe are living with advanced non-alcoholic steatohepatitis (NASH), the most severe form of non-alcoholic fatty liver disease (NAFLD) and a major risk factor for liver transplant and the development of primary liver cancer. The incidence of NAFLD is expected to increase more than 21% by 2030, with a concomitant increase of more than 63% in the incidence of NASH in the same period.

https://globenewswire.com/news-release/2018/11/05/1644726/0/en/Exalenz-to-Present-Positive-Clinical-Data-for-the-Breath-ID-13C-Methacetin-Breath-Test-System-at-the-Liver-Meeting-2018.html

Novartis, Pfizer join forces on potentially lucrative fatty liver disease

Novartis, Pfizer join forces on potentially lucrative fatty liver disease
John Miller, Michael Erman

ZURICH/NEW YORK (Reuters) - Novartis AG and Pfizer Inc are teaming up to develop treatments for a liver disease many drug companies believe will become a hugely lucrative market, as it is tied to the obesity and diabetes epidemics.

The Swiss and U.S. drugmakers announced on Monday that they will collaborate to develop combination therapies involving medicines they have been working on separately to treat nonalcoholic steatohepatitis, or NASH.

Though hardly a household name, the progressive fatty liver disease with no approved treatments is poised to become the leading cause of liver transplants by 2020. 

Continue reading......

Cirius Therapeutics Reports On Phase 2b Trial in NASH Patients with Fibrosis

Cirius Therapeutics Reports Positive Data for MSDC-0602K in Interim Analysis of Phase 2b Clinical Trial in NASH Patients with Fibrosis

- Interim analysis showed statistically significant reductions in liver enzymes, including ALT and AST, measured from baseline at six months

- In two highest dose groups, at least 50% of patients with high baseline ALT or AST improved to normal range at six months

- Statistically significant reductions in HbA1c and other measures of glycemic control and insulin resistance were observed

- Overall adverse event rate was similar across placebo and all doses of MSDC-0602K

- Largest Phase2b clinical trial including paired biopsies conducted in NASH; biopsy data after 12 months of treatment expected to be reported in the second half of 2019

SAN DIEGO and KALAMAZOO, Mich., Oct. 25, 2018 /PRNewswire/ -- Cirius Therapeutics today announced positive results from an interim analysis of exploratory endpoints from its ongoing, fully enrolled Phase 2b clinical trial (the EMMINENCE trial) evaluating MSDC-0602K in 402 patients diagnosed with non-alcoholic steatohepatitis (NASH) with fibrosis. The interim analysis, which was conducted in the first 328 patients to reach their six-month follow-up visit, showed that patients treated with MSDC-0602K had significant improvements from baseline in measures of liver function and insulin resistance at six months. MSDC-0602K, a second-generation insulin sensitizer, is designed to selectively modulate the mitochondrial pyruvate carrier (MPC), which at the cellular level mediates the effects of overnutrition, a major cause of NASH and other metabolic disorders.

The subjects included in this interim analysis had significant liver disease, as established by liver biopsy, with an average non-alcoholic fatty liver disease (NAFLD) activity score at baseline of 5.3. Almost sixty percent of these subjects had a baseline fibrosis score of 2 or 3 and approximately fifty percent also had a diagnosis of Type 2 diabetes at baseline. Overall, baseline characteristics were well-balanced across treatment groups.

Key findings from the interim analysis include improvements in liver enzymes, with placebo-corrected reductions at 6 months of 14.3 U/L (p<0.001) and 7.9 U/L (p=0.012) in ALT and AST, respectively, in the 125mg cohort, and 10.6 U/L (p=0.004) and 4.0 (NS) in ALT and AST, respectively, in the 250mg cohort. Placebo-corrected reductions, relative to baseline, were 25% and 18% in ALT and AST, respectively, in the 125mg cohort, and 19% and 9% in ALT and AST, respectively, in the 250mg cohort. Importantly, normalization of hepatic enzymes was observed across all three dose levels of MSDC-0602K. 

Percentage of patients with high baseline values who returned to normal range
	Placebo	62.5mg	125mg	250mg
ALT	15%	29%	60%	56%
AST	20%	36%	50%	52%

*ALT normal range defined as 6-34 U/L and 6-43 U/L for women and men, respectively; AST normal range defined as 9-34 U/L and 11-36 U/L for women and men, respectively) 

"We believe these interim results around improved measures of liver function and glycemic control, together with the preliminary adverse event profile, support MSDC-0602K's potential to be used in the treatment of NASH with fibrosis, including for those patients with Type 2 diabetes, a group which represents approximately 50% of patients with NASH," said Cirius' chief medical officer Howard Dittrich, M.D. "These results support the view that therapies directed toward the MPC have the potential to achieve insulin sensitizing pharmacology with an improved profile over first generation insulin sensitizers. We look forward to presenting full data to the scientific community." 

In addition to the improvement in ALT and AST, observations included significant improvement at six months in fasting glucose, HbA1c, insulin levels and HOMA-IR at the 125mg and 250mg dose levels.  Significant improvement in HbA1c was also observed in subjects with a diagnosis of Type 2 diabetes in the 125mg and 250mg cohorts.  

In this interim analysis, the overall rate of treatment emergent adverse events was similar across placebo and all MSDC-0602K cohorts. There was a higher rate of treatment emergent adverse events reported in the 250mg dose compared to placebo in the musculoskeletal and connective tissue disorders category. Within this category, arthralgia and back pain were the most frequently reported individual adverse events across the pooled 328 subjects. A modest dose-dependent increase in body weight was seen in MSDC-0602K treated subjects, a finding seen with insulin and with other therapies that seek to improve insulin resistance. The rate of peripheral edema observed at six months was similar to that observed at baseline and was comparable across placebo and all MSDC-0602K cohorts. 

"The interim results from the EMMINENCE trial, the largest Phase 2b clinical trial to include paired biopsies ever conducted in NASH, are compelling," said Stephen Harrison, M.D., the principal investigator in the EMMINENCE trial. "The improvements in hepatic enzymes observed to date are impressive, especially when combined with the meaningful improvements in glycemic control." 

About the EMMINENCE Trial

The EMMINENCE trial is a 12-month, randomized, double-blind, placebo-controlled trial evaluating three oral dose levels of MSDC-0602K. Endpoints of the clinical trial include hepatic histological changes measured by biopsy after 12 months of treatment, changes in liver and metabolic function measured by the liver enzymes ALT and AST, markers of liver fibrosis, glycemic control and safety and tolerability. Not all of these endpoints were examined in this interim analysis; rather, in addition to the safety variables of incidence of treatment-emergent adverse events and  peripheral edema grades, changes from baseline relative to placebo for a number of endpoints, including liver functions tests such as ALT and AST, among others, biomarkers and indirect measures of apoptosis and fibrosis, circulating inflammatory markers and markers of bone metabolism, serum triglycerides and fasting cholesterol, markers of insulin sensitivity, and blood pressure, were examined in an exploratory manner. 

About Cirius Therapeutics

Cirius is a clinical-stage pharmaceutical company focused on the development and commercialization of innovative therapies for the treatment of liver and metabolic diseases. Our lead product candidate, MSDC- 0602K, is a novel small molecule being developed as a once-daily oral therapy to treat NASH with fibrosis. MSDC-0602K is designed to selectively modulate the MPC, which mediates at the cellular level the effects of overnutrition, a major cause of NASH and other metabolic disorders. We are conducting a Phase 2b clinical trial of MSDC-0602K, which we have fully enrolled with 402 patients diagnosed with NASH with fibrosis. We expect to report final data from this clinical trial in the second half of 2019.

SOURCE Cirius Therapeutics

FibroScan after endoscopy found undiagnosed NAFLD, NASH

FibroScan after endoscopy found undiagnosed NAFLD, NASH
October 11, 2018

PHILADELPHIA — FibroScan screening for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis could significantly improve patient diagnosis and care, as data presented at the American College of Gastroenterology Annual Meeting showed that FibroScan found a significant number of undiagnosed cases.

Read the article:

https://www.healio.com/gastroenterology/liver-biliary-disorders/news/online/%7Be476783c-5949-44a6-9ad3-bc721a999b35%7D/fibroscan-after-endoscopy-found-undiagnosed-nafld-nash

Meeting Coverage

See more from American College of Gastroenterology Annual Meeting

Oramed; First patient enrolled in study of oral insulin capsule for NASH

Oramed Enrolls First Patient in Its Clinical Study for Oral Insulin in the Treatment of NASH

NEW YORK, Oct. 4, 2018 /PRNewswire/ — Oramed Pharmaceuticals Inc. (NASDAQ: ORMP) (TASE: ORMP) (www.oramed.com), a clinical-stage pharmaceutical company focused on the development of oral drug delivery systems, announced today it has enrolled the first patient in an exploratory clinical study of its oral insulin capsule, ORMD-0801, in the treatment of nonalcoholic steatohepatitis (NASH).

The three-month treatment study, recently approved by Israel’s Ministry of Health, will assess the effectiveness of ORMD-0801 in reducing liver fat content, inflammation and fibrosis in patients with NASH.

Data from preclinical studies and clinical studies of ORMD-0801 demonstrate Oramed’s oral insulin capsule has the potential to reduce inflammation of the liver.

“Prevalence of NASH is accelerating rapidly and correlates directly with the rising incidence of type 2 diabetes. As we continue our focus on the development of our oral insulin for the treatment of diabetes, we are excited about its potential in this greatly needed NASH indication,” stated Oramed CEO, Nadav Kidron.

NASH, a chronic liver disease caused by excessive fat in the liver, can lead to fibrosis, cirrhosis, liver failure and death. According to the Journal of Hepatology, prevalent NASH cases are expected to increase 63% from 16 million in 2015 to 27 million cases in 2030.

About Oramed Pharmaceuticals 

Oramed Pharmaceuticals is a technology pioneer in the field of oral delivery solutions for drugs currently delivered via injection. Established in 2006, Oramed’s Protein Oral Delivery (PODTM) technology is based on over 30 years of research by top scientists at Jerusalem’sHadassah Medical Center. Oramed is seeking to revolutionize the treatment of diabetes through its proprietary flagship product, an orally ingestible insulin capsule (ORMD-0801). The Company completed multiple Phase II clinical trials under an Investigational New Drug application with the U.S. Food and Drug Administration. In addition, Oramed is developing an oral GLP-1 analog capsule (ORMD-0901).

https://www.oramed.com/oramed-enrolls-first-patient-in-its-clinical-study-for-oral-insulin-in-the-treatment-of-nash/