Monday, February 18, 2019

The Year in Viral Hepatitis: Part 1

Gastroenterology & Endoscopy News
The Year in Viral Hepatitis: Part 1
Feb 18, 2019
Although 2018 saw no major drug approvals or dramatic breakthroughs for viral hepatitis, researchers continued to make progress against these infections. We asked Drs. Ira Jacobson and Saikiran Kilaru for an overview of the most important findings reported last year.

*** Free registration may be required to view article

Friday, February 15, 2019

Hepatitis C and HIV/AIDS Medications Costliest Group of Outpatient Prescription Drugs for Medicaid

Kaiser Family Foundation
Analysis Finds that Medications for Hepatitis C and HIV/AIDS Are the Costliest Group of Outpatient Prescription Drugs for Medicaid, While Diabetes Drugs Have Posted the Sharpest Rise in Costs 
Chris Lee
Published: Feb 15, 2019
Antiviral medications, including those that treat hepatitis C and HIV/AIDS, cost the Medicaid program more money (before rebates) than any other group of outpatient prescription drugs for each year from 2014 to 2017, according to a new KFF analysis.

The analysis of utilization and spending trends finds that antivirals accounted for more than 13 percent of the $63.6 billion in Medicaid outpatient drug spending pre-rebates in 2017 — a level disproportionate to their utilization and a reflection of the high cost of these drugs. Drugs for diabetes were the second most costly group that year, accounting for 10 percent of Medicaid outpatient drug spending before rebates. Spending for diabetes drugs rose faster than for any other group, nearly doubling from 2014 to 2017 — largely due to the rising price of insulin.




On This Blog 
Link to research and news articles addressing the high cost of hepatitis C drugs; insurance restrictions implemented by private insurers/Medicaid/Medicare and the effectiveness, safety and availability of generic versions of hepatitis C medications. 

Thursday, February 14, 2019

Direct-acting antivirals reduce risk of premature mortality and liver cancer for people with chronic hepatitis C

Page updated with additional links on Feb 14, 2019

The Lancet
Published: February 11, 2019
DOI: https://doi.org/10.1016/S0140-6736(18)32111-1
Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatment: a prospective cohort study
Although direct-acting antivirals have been used extensively to treat patients with chronic hepatitis C virus (HCV) infection, their clinical effectiveness has not been well reported. We compared the incidence of death, hepatocellular carcinoma, and decompensated cirrhosis between patients treated with direct-acting antivirals and those untreated, in the French ANRS CO22 Hepather cohort.
Continue to "full-text article"
PDF shared on twitter by @HenryEChang

Direct-acting antiviral treatment for hepatitis C - Linked Comment
Writing in a linked Comment, Dr Raymond T Chung, Director of the Liver Center at Massachusetts General Hospital, USA, says: 
"The study by Carrat and colleagues offers substantive evidence that cure of HCV delivered by all-oral direct-acting antiviral regimens is associated with clinical benefits. These findings firmly counter those of a Cochrane review of direct-acting antiviral treatment trials that could neither confirm nor reject if direct-acting antivirals had an effect on long-term HCV-related morbidity and mortality. They also provide the best evidence to date to support guidance documents that recommend direct-acting antiviral treatment for all patients with chronic HCV infection. Finally, they provide credence to the achievability of the goals set out by WHO, not only to eliminate HCV but also to substantially reduce its complications." 
Read full comment here....

Media Coverage
Patient-friendly article
Feb 14, 2019
Scientists have firmly established an association between direct-acting antiviral treatment and a lower risk of liver cancer and death.

Feb 11, 2019
Direct-acting antivirals reduce risk of premature mortality and liver cancer for people with chronic hepatitis C 
Professor Fabrice Carrat of the Sorbonne Université, France, said: "Taking a large cohort like this provides the opportunity to evaluate the effect of direct-acting antiviral therapy on the long-term outcomes of patients with hepatitis C. We saw a reduction of risk for complications related to the disease, and to mortality, and believe this treatment should be considered for all patients with chronic hepatitis C infection."

The first prospective, longitudinal study investigating treatment of chronic hepatitis C with direct-acting antivirals finds that the treatment is associated with reduced risk of mortality and liver cancer, according to a study published in The Lancet.

The research is the first to demonstrate the clinical effectiveness of direct-acting antivirals on the disease and suggests that they should be considered for all patients with chronic hepatitis C infection.

For ethical reasons a trial with a control arm is not possible and researchers approached this by setting up an observational study of around 10,000 patients. At follow up, about three-quarters had been treated with direct-action antivirals and a quarter were untreated. The incidence of death and hepatocellular carcinoma - the most common form of liver cancer - were significantly decreased in patients who were treated. Their risk of decompensated cirrhosis was not reduced by the treatment.

Around the world, an estimated 71 million people are chronically infected with the hepatitis C virus (HCV). The infection causes complications such as cirrhosis, liver disease, hepatocellular carcinoma, and many people die as a result. Over the last 15 years, these complications have tripled and models predict they will peak between 2030 and 2035. The World Health Organization (WHO) has set targets for the elimination of hepatitis C, and a reduction of related complications. Recently, a modelling study published in The Lancet found that major progress towards these targets by 2030 is possible, but will require vast improvements in screening, prevention, and treatment [1].

Previous work has shown there is a reduction of risk for complications and mortality in patients who are treated with interferon or direct-acting antivirals, but few studies have compared treated and untreated patients. The aim of direct-acting antiviral drugs is to achieve a sustained virological response, meaning that the virus is undetectable in the blood of the patients. A recent Cochrane Review [2] found no evidence for or against the treatment having a long-term effect on death and disease, so this large study is timely, and may help doctors and patients with treatment plans.

In this study, 10,166 patients were recruited from 32 centres in France. At a median of 33 months, 9,895 patients had available follow up information and were included in the analysis, with 7,344 treated with direct-acting antivirals and 2,551 untreated. During follow-up, 218 patients died (129 treated, 89 untreated), 258 reported hepatocellular carcinoma (187 treated, 71 untreated), and 106 had decompensated cirrhosis (74 treated, 32 untreated).

Overall, the study finds that direct-acting antiviral treatment is associated with reduced risk for global mortality and hepatocellular cancer, but not decompensation of cirrhosis. The researchers initially found an increase in risk associated with treatment with direct-acting antiviral treatment, but once they had adjusted for variables such as age, sex, body-mass index, severity of liver disease, geographical origin, infection route and other factors, they found a reduced risk.

Patients who were treated were 52% less likely to die prematurely than people who were not treated (the estimated adjusted risk of death at one year in untreated patients in the cohort is 84 deaths per 10,000 patients, and in those who were treated was 40 per 10,000), and 33% less likely to present with hepatocellular carcinoma (the estimated adjusted risk of developing hepatocellular carcinoma within a year in untreated patients in the cohort was 129 cases per 10,000 patients, and 86 per 10,000 in people who were treated). [3]

In a subgroup of 3,045 patients with cirrhosis at baseline, the same association was found for mortality and hepatocellular cancer, provided the patients achieved an undetectable level of HCV in their blood. The researchers believe this is because the treatment induces a sustained virological response, allowing the liver to regenerate which decreases risk.

Professor Fabrice Carrat of the Sorbonne Université, France, said: "Taking a large cohort like this provides the opportunity to evaluate the effect of direct-acting antiviral therapy on the long-term outcomes of patients with hepatitis C. We saw a reduction of risk for complications related to the disease, and to mortality, and believe this treatment should be considered for all patients with chronic hepatitis C infection." [4]

In the study, only a few patients underwent liver biopsy to confirm cirrhosis, with platelet levels or prothrombin time - a blood test - used to classify whether a patient had cirrhosis or not. A validation study using other non-invasive markers of fibrosis suggested that their methods correctly classified cirrhosis in the patients.

Patients who received more than one course of direct-acting antivirals were considered to have had continuous exposure, even where there may have been a lag time or if the first course may not have been associated with sustained virological response. This should have underestimated the response to the drugs rather than overestimated them so does not affect the result.

The study excluded patients with a history of decompensated cirrhosis and liver transplantation and these are the patients who would be at highest risk for complications. The potential benefits of treatment in this group could be underestimated because of their exclusion, as trial data shows improvements in liver function in patients with decompensated cirrhosis who achieved a sustained virological response.
https://www.eurekalert.org/pub_releases/2019-02/tl-pss020819.php

Recommended Reading
lastair Heffernan, MResProf Graham S Cooke, DPhilShevanthi Nayagam, PhDProf Mark Thursz, MDProf Timothy B Hallett, PhD
Jan 28, 2019
The revolution in hepatitis C virus (HCV) treatment through the development of direct-acting antivirals (DAAs) has generated international interest in the global elimination of the disease as a public health threat. In 2017, this led WHO to establish elimination targets for 2030. We evaluated the impact of public health interventions on the global HCV epidemic and investigated whether WHO's elimination targets could be met.

Netflix Model -Countries Use Novel Strategies to Tackle Price of HCV Drugs

Countries Use Novel Strategies to Tackle Price of HCV Drugs
Roxanne Nelson, RN, BSN
February 14, 2019
A recent study suggests that the WHO's goal of eliminating HCV infections worldwide by 2030 is potentially feasible but faces some daunting challenges, including the cost of DAAs.
To help overcome some of the barriers to treatment access, Australia and Brazil are each exploring innovative methods to circumvent the cost. Two perspective articles published February 14 in the New England Journal of Medicine outline how they hope to accomplish this goal.
The healthcare system in Australia is complex but is generally funded by the government. Drugs that are on the national formulary are usually paid for by the government. To help make DAAs more affordable to patients and the healthcare system, the Australian government has rolled out a strategy, nicknamed the "Netflix" plan because it is similar to the movie subscription service, in which payment is for bulk access.
Read more: https://www.medscape.com/viewarticle/909083 

New England Journal of Medicine
Perspective
Universal Medicine Access through Lump-Sum Remuneration — Australia’s Approach to Hepatitis C
Suerie Moon, M.P.A., Ph.D., and Elise Erickson, M.A.
High prices can restrict access to medicines in rich and poor countries alike. Australia’s approach to providing direct-acting antivirals (DAAs) for patients with hepatitis C virus (HCV) suggests that, under certain conditions, innovative approaches to payment can remove price as a barrier to access. In Australia, medicines on the national formulary are largely paid for by the government. In 2015, the authorities negotiated an agreement to spend approximately 1 billion Australian dollars (U.S.$766 million) over 5 years in exchange for an unlimited volume of DAAs for HCV from suppliers. This approach has been called the “subscription” or “Netflix” model, and the state of Louisiana announced in January 2019 that it was pursuing a similar approach for HCV. The Australian agreement is confidential, though the basic information above has been publicly reported..
Read more: https://www.nejm.org/doi/full/10.1056/NEJMp1813728?query=TOC 

New England Journal of Medicine
Brazil’s strategy for addressing hepatitis C, which combines evidence-based treatment protocols and innovative initiatives for local production of generic direct-acting antiviral drugs, needs to be considered in light of ongoing conflicts over pharmaceutical patents.
Payment may be required to view article. 

Wednesday, February 13, 2019

Cirrhosis: What Clinicians Need to Know

Cirrhosis: What Clinicians Need to Know
Listen to Christine Kerr, MD, AAHIVS, of Hudson River HealthCare, discuss specific challenges in managing cirrhosis in an easy to access webinar using a case-based patient scenario, provided by HepCure.

Although; Cirrhosis: What Clinicians Need to Know, is intended for physicians and health care professionals, anyone, especially patients will benefit from watching the presentation.


Learning Objectives
1. Describe cirrhosis.
2. Discuss screening guidelines and diagnostic algorithms for cirrhosis.
3. Review cirrhosis treatment best practices.
Begin here....

View All Presentations At HepCure
Webinar Archive 

Christine Kerr, MD, AAHIVS, is the medical director for the HIV and Hepatitis Programs for Hudson River HealthCare. She trained in internal medicine at Brown University and Infectious Disease at Harvard. She is the community co-chair for the New York State Hepatitis C Elimination Task force, the co-chair of the NYS AIDS institute Quality Advisory committee and is co-chair for the NYS AIDS Institute/Johns Hopkins Guidelines Committee for Treatment of Hepatitis C in the Primary Care Setting. Her areas of interest include treatment of HIV and Hepatitis C in the community setting, care of the underserved, and program development and evaluation.

Tuesday, February 12, 2019

Eating lots of meat tied to higher risk of liver disease

Reuters• February 12, 2019
By Lisa Rapaport
(Reuters Health) - People who eat a lot of animal protein may be more likely to have excessive fat in their livers and a higher risk of liver disease than individuals whose main source of protein is vegetables, a Dutch study suggests.

Researchers focused on what's known as non-alcoholic fatty liver disease (NAFLD), which is usually associated with obesity and certain eating habits. While dietary changes are recommended to treat this type of liver disease, research to date hasn't clearly demonstrated whether these changes can work for prevention.

Read more: 
https://news.yahoo.com/eating-lots-meat-tied-higher-risk-liver-disease-231806194.html

Study:
Association of dietary macronutrient composition and non-alcoholic fatty liver disease in an ageing population: the Rotterdam Study 

Monday, February 11, 2019

FDA announcing a new plan to strengthen regulation of dietary supplements

Your multivitamins and brain-boosting pills may be suspect, and regulators are cracking down on the $40 billion industry
Erin Brodwin 
On Monday, Scott Gottlieb, the head of the Food and Drug Administration (FDA), announced a series of steps his agency would take in coming months to crack down on manufacturers that tout the ability of their formulas to do everything from increase energy to cure cancer. Of particular concern, he said in a statement, are pills that claim to treat Alzheimer's, a serious brain disease that hinders memory and has no cure. 
Read more, here....

Statement from FDA Commissioner Scott Gottlieb, M.D., on the agency’s new efforts to strengthen regulation of dietary supplements by modernizing and reforming FDA’s oversight

The use of dietary supplements, such as vitamins, minerals or herbs, has become a routine part of the American lifestyle. Three out of every four American consumers take a dietary supplement on a regular basis. For older Americans, the rate rises to four in five. And one in three children take supplements, either given to them by their parents or, commonly in teens, taking them on their own.

That’s why today we are announcing a new plan for policy advancements with the goal of implementing one of the most significant modernizations of dietary supplement regulation and oversight in more than 25 years.

I’ve personally benefited from the use of dietary supplements and, as a physician, recognize the benefits of certain supplements as a part of a comprehensive care plan. It’s clear to me that dietary supplements play an important role in our lives as we strive to stay healthy. It’s also clear that the U.S. Food and Drug Administration plays an important role in helping consumers make use of safe, high-quality dietary supplements while also protecting Americans from the potential dangers of products that don’t meet the agency’s standards for marketing.

In the 25 years since Congress passed the Dietary Supplement Health and Education Act (DSHEA), the law that transformed the FDA’s authority to regulate dietary supplements, the dietary supplement market has grown significantly. What was once a $4 billion industry comprised of about 4,000 unique products, is now an industry worth more than $40 billion, with more than 50,000 – and possibly as many as 80,000 or even more – different products available to consumers.

DSHEA imposes a number of requirements around the manufacture and labeling of dietary supplements. We know that most players in this industry act responsibly. But there are opportunities for bad actors to exploit the halo created by quality work of legitimate manufacturers to instead distribute and sell dangerous products that put consumers at risk. As the popularity of supplements has grown, so have the number of entities marketing potentially dangerous products or making unproven or misleading claims about the health benefits they may deliver.

Making healthy choices about diets can have a significant and positive impact on Americans’ health. To be able to make those choices with respect to dietary supplements, consumers need to have access to safe, well-manufactured, and appropriately labeled products. One of my top goals is ensuring that we achieve the right balance between preserving consumers’ access to lawful supplements, while still upholding our solemn obligation to protect the public from unsafe and unlawful products, and holding accountable those actors who are unable or unwilling to comply with the requirements of the law.

Today, we’re announcing new steps we intend to advance to achieve these twin goals. These steps include communicating to the public as soon as possible when there is a concern about a dietary supplement on the market, ensuring that our regulatory framework is flexible enough to adequately evaluate product safety while also promoting innovation, continuing to work closely with our industry partners, developing new enforcement strategies and continuing to engage in a public dialogue to get valuable feedback from dietary supplement stakeholders.

The opportunity to strengthen the framework that governs dietary supplements couldn’t come at a more pivotal time. On the one hand, advances in science and the growth and development in the dietary supplement industry carries with it many new opportunities for consumers to improve their health. At the same time, the growth in the number of adulterated and misbranded products – including those spiked with drug ingredients not declared on their labels, misleading claims, and other risks – creates new potential dangers.

Legitimate industry benefits from a framework that inspires the confidence of consumers and providers. Patients benefit from products that meet high standards for quality.

I’m concerned that changes in the supplement market may have outpaced the evolution of our own policies and our capacity to manage emerging risks. To continue to fulfill our public health obligations we need to modernize and strengthen our overall approach to these products. Toward these goals, the FDA is committing to new priorities when it comes to our oversight of dietary supplements at the same time that we carefully evaluate what more we can do to meet the challenge of effectively overseeing the dietary supplement market while still preserving the balance struck by DSHEA.

As part of our comprehensive efforts, today we sent 12 warning letters and five online advisory letters to companies whose products, many of which are marketed as dietary supplements, are being illegally marketed as unapproved new drugs because the products bear unproven claims to prevent, treat or cure Alzheimer’s disease, as well as a number of other serious diseases and health conditions, including diabetes and cancer. Products intended to treat Alzheimer’s disease must gain FDA approval before they are sold in order to help ensure they are safe and effective for their intended medical use. Dietary supplements can, when substantiated, claim a number of potential benefits to consumer health, but they cannot claim to prevent, treat or cure diseases like Alzheimer’s. Such claims can harm patients by discouraging them from seeking FDA-approved medical products that have been demonstrated to be safe and effective for these medical conditions. In recent years, we’ve also taken action against companies and dietary supplements making similar claims regarding treatment of serious conditions such as cancer and opioid addiction. These enforcement actions are just one part of our overall efforts to update our policy framework governing dietary supplements.

At the FDA, we have an obligation to ensure that we’re using the resources that we have as efficiently and effectively as we can, and as we engage in discussions about whether our existing resource levels are adequate, I take that obligation very seriously. That’s why I recently directed the establishment of a Dietary Supplement Working Group at the FDA, led out of my office and comprised of representatives from multiple centers and offices across the agency. I’ve tasked this group with taking a close look at our organizational structures, processes, procedures and practices in order to identify opportunities to modernize our oversight of dietary supplements.

Additionally, when the FDA created the Office of Dietary Supplement Programs (ODSP) three years ago, the agency recognized that keeping up with the evolving marketplace meant giving dietary supplement regulation more attention and making it a higher priority. One of the things that this office has done is to articulate the FDA’s strategic priorities on dietary supplements to ensure that we’re focusing our attention and using our resources in ways that make sense.

Our first priority for dietary supplements is ensuring safety. Above all else, the FDA’s duty is to protect consumers from harmful products. Our second priority is maintaining product integrity: we want to ensure that dietary supplements contain the ingredients that they’re labeled to contain, and nothing else, and that those products are consistently manufactured according to quality standards. Our third priority is informed decision-making. We want to foster an environment where consumers and health care professionals are able to make informed decisions before recommending, purchasing or using dietary supplements.

In the coming months, we’ll be providing additional details on the steps we are taking to continue moving our dietary supplement program forward to implement these priorities. Our new approach benefits consumers by balancing new policies to promote innovation and efficiency in the marketplace for dietary supplements with increased steps to protect the public from potential safety issues.

Today, I’m also announcing the first of several important steps to help advance our important policy goals. Among the steps that we’re considering or actively formulating, first are new ways to communicate more quickly when we have concerns that an ingredient is unlawful and potentially dangerous and should not be marketed in dietary supplements. We’re developing a new rapid-response tool to alert the public so consumers can avoid buying or using products with that ingredient, and to notify responsible industry participants to avoid making or selling them.

Second, we also need to ensure that our regulatory framework is flexible enough to adequately evaluate product safety while promoting innovation. The key to this effort will be important steps to foster the submission of new dietary ingredient (NDI) notifications. An effective NDI notification process represents the FDA’s only opportunity to evaluate the safety of a new ingredient before it becomes available to consumers and helps promote transparency and risk-based allocation of resources. We’re continuing to develop guidance for preparing NDI notifications to ensure FDA can thoroughly review the safety of these ingredients. In conjunction with this effort, we’re planning to update our compliance policy regarding NDIs.

We know these are important and timely issues and we’re also planning a public meeting this spring on the topic of responsible innovation in the dietary supplement industry. I expect the feedback received during this meeting will be essential as we move to modernize our approach toward NDIs. We’ll look to address other challenges that may act as barriers to dietary supplement innovation and safety including issues such as what the right incentives might be for establishing dietary supplement exclusivity, and the scope of permitted dietary ingredients. We invite all our stakeholders to share their views on how the FDA should strengthen the dietary supplement program for the future. So, please stay tuned for more information regarding registration and logistics.

Third, as with other commodities that the agency regulates, it’s critical that the FDA continue to work closely with our partners in industry to achieve our primary goal of protecting public health and safety. As the dietary supplement industry develops new products and ingredients, advances new delivery systems and innovates in other ways, the FDA must do more to leverage its existing resources and authorities to evaluate these products. This requires collaborative research and a shared understanding. I’m pleased to announce that we’ve recently created the Botanical Safety Consortium, a public-private partnership that will gather leading scientific minds from industry, academia and government to promote scientific advances in evaluating the safety of botanical ingredients and mixtures in dietary supplements. This group will look at novel ways to use cutting-edge toxicology tools, including alternatives to animal testing, to promote the goals of safety and effectiveness we share with consumers and other stakeholders.

Fourth, we’ll continue to take actions to protect public health – like those we took today for illegal Alzheimer’s disease products – and develop new enforcement strategies, as a key element of our approach to protecting consumers as the risks evolve. We’re already making our internal processes more efficient for taking enforcement action when products claiming to be supplements contain unlawful ingredients, including drug ingredients. For example, last April we took strong action to protect consumers from the dangers of dietary supplement products marketed in bulk and containing pure and highly concentrated caffeine. We warned consumers in November to not purchase Rhino male enhancement products because they were unapproved new drugs that contained sildenafil and/or tadalafil, which are among active ingredients in the FDA-approved prescription drugs Viagra and Cialis. During the same month, we issued warnings to companies for unlawfully marketing as dietary supplement products that contained a compound called tianeptine; these products were unapproved new drugs that bore unproven claims that the products could be used to treat opioid addiction. We’ve also been active with compliance and enforcement efforts against firms that have shown persistent inability to comply with the current good manufacturing practice requirements for dietary supplements, and taking action to protect the public against unsafe imports and recalled products.

Finally, we’ll engage a public dialogue around whether additional steps to modernize DSHEA are necessary. We’ve heard from stakeholders who want to open such a dialogue. While the FDA is committed to leveraging its existing resources and authorities to the fullest extent possible, we believe there may be value in a broader public conversation about whether certain changes to the law might be helpful. We believe there may be opportunities to modernize DSHEA for the future, while preserving the law’s essential balance. For example, some stakeholders have suggested that the statute should be amended to establish avenues for dietary supplement exclusivity and add a product listing requirement. A mandatory listing requirement could provide significant benefits by improving transparency in the marketplace and promoting risk-based regulation. It could also help facilitate efficient enforcement of the law and establish new mechanisms to identify bad actors who put the public at risk and undermine consumer confidence in the entire industry.

We’re interested in hearing other ideas our stakeholders may have, and not just those limited to changes to the law, so we can go about the task of regulating this space in a way that reflects where the industry is today, and continue to safeguard consumers’ ability to access safe, compliant dietary supplements for the next 25 years. For example, is it possible to design a product listing regime that helps us protect consumers and level the playing field for responsible industry participants by making it easier for us to take swift action against illegitimate and dangerous products, such as products that are tainted with drug ingredients? And is it possible to do this without disrupting the balance struck by DSHEA, and without imposing any significant new burdens on responsible firms? The answer to these questions may very well be yes. And if that’s the case, these are absolutely things that we should be talking about.

I’m confident that the efforts we’re announcing today, and the ones that we’ll continue to advance in the months and years to come, will help us achieve these goals on behalf of consumers. The steps outlined today highlight both where we are currently and where we look forward to moving toward. We are eager to continue our work with both our industry partners and dietary supplement consumers and will announce more upcoming ideas that we hope to roll out in the near future.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

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.