Published on Nov 9, 2014
AASLD TV was pleased to discuss this topic which perhaps doesn’t get enough attention. Moderators Mario Strazzabosco, MD, PhD and Guadalupe Garcia-Tsao, MD talk about the importance of returning the practice of hepatology to its appropriate focus: enabling health and effective care of patients with liver disease and how doing so can significantly impact the value of patient outcomes.
Source WebsEdgeHealth
Published on Nov 9, 2014
New Treatments for Hepatitis C Moderator Hugo Rosen, MD, FACP talks to AASLD TV about this exciting session concerning current and emerging regimens for treatment of HCV as well as how to identify patients at risk of developing HCV-related hepatocellular carcinoma.
Source WebsEdgeHealth
Merck Plans to Initiate Phase 2 C-CREST Program to Evaluate Merck’s Triple Combination of Grazoprevir/Elbasvir with MK-3682 (formerly IDX21437), a Novel Nucleotide Inhibitor, in Q1 2015
Sunday, November 9, 2014 6:53 pm EST
BOSTON--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the presentation of interim data from the C-SWIFT study exploring the potential of a candidate triple-therapy regimen consisting of the fixed-dose combination of grazoprevir/elbasvir (MK-5172/MK-8742, MK-5172A), the company’s investigational NS3/4A protease inhibitor and NS5A inhibitor, in combination with sofosbuvir, a nucleotide (NS5B) inhibitor for the treatment of chronic hepatitis C virus (HCV) infection. Preliminary findings in treatment-naïve HCV genotype 1- (GT1) infected non-cirrhotic patients, following six and four weeks of treatment, and patients with cirrhotic disease, following eight and six weeks of treatment, will be presented by Dr. Eric Lawitz, vice president, scientific and research development, The Texas Liver Institute, San Antonio, TX and C-SWIFT lead investigator. This poster presentation is part of a late-breaking abstract session at the 65th American Association for the Study of Liver Diseases (AASLD) Annual Meeting, also known as The Liver Meeting®.
“These interim data provide a compelling proof-of-concept for the potential of an eight- or six-week triple therapy course in treatment-naive patients with genotype 1 disease, including cirrhotic patients,” said Dr. Lawitz. “These findings will inform the design of larger studies aimed at understanding the potential of short-duration triple therapy across multiple patient types.”
To date, the investigational triple therapy has shown response rates (sustained virologic response1 [SVR] at 4/8 weeks following therapy) ranging from 80 percent to 94.7 percent in cirrhotic and non-cirrhotic patients following six and eight weeks of treatment in this study, as shown in table 1. The four-week regimen resulted in sub-optimal efficacy.
All 28 patients not achieving SVR4/8 relapsed following the end of therapy. Of these patients, 25 (89%) were genotype 1a (GT1a) and three (11%) were genotype 1b (GT1b) [82% of enrolled subjects were infected with HCV GT1a at baseline]. Sequence analysis of virologic failures is so far available for 23 patients. Wild type virus was determined to be the cause in 12 of the relapsed patients. In the other relapsed patients, 10 had elbasvir-resistant viral variants and one had a variant resistant to both grazoprevir and elbasvir.
In this study, the co-administration of grazoprevir/elbasvir and sofosbuvir was generally well-tolerated. The most common adverse events associated with the triple regimen were: headache (4%), fatigue (2%) and nausea (2%). One patient withdrew from the study for reasons unrelated to treatment.
“Our goal is to establish a simple, effective, well-tolerated regimen that is applicable across the diverse population of patients with HCV,” said Dr. Eliav Barr, vice president, infectious diseases, Merck Research Laboratories. “The preliminary data provide us with the confidence to initiate our C-CREST study to evaluate a triple combination comprising Merck’s investigational candidates from three major therapeutic classes of HCV medicines.”
About C-SWIFT
The C-SWIFT study enrolled a total of 102 treatment-naïve patients with HCV genotype 1 (GT1a and GT1b) infection at The Texas Liver Institute, San Antonio, TX. Treatment-naïve, non-cirrhotic patients were randomized to receive the fixed-dose combination of grazoprevir/ elbasvir (one pill containing 100 mg, 50 mg respectively) plus the nucleotide inhibitor sofosbuvir (400 mg) once daily for eight, six or four weeks. Similarly, treatment-naïve, cirrhotic patients were randomized to receive the investigational combination for either eight or six weeks. The primary endpoint of the study is the percentage of patients achieving sustained virologic response 12 weeks after the completion of therapy (SVR12). An additional analysis of patients with genotype 3 (GT3) HCV enrolled in the C-SWIFT study will be presented at a future scientific congress.
About C-CREST
Based upon the interim findings from C-SWIFT and data from the Phase 1 clinical trial for MK-3682, also presented at The Liver Meeting®, Merck plans to initiate Phase 2 clinical trials evaluating the efficacy and safety of two short-duration triple therapy regimens: MK-3682 in combination with grazoprevir/elbasvir; and MK-3682 in combination with grazoprevir and Merck’s investigational early-stage NS5A inhibitor MK-8408, in non-cirrhotic HCV patients. Part A of the Phase 2 studies is planned to evaluate eight weeks of therapy among non-cirrhotic HCV-infected patients, and Part B studies may evaluate shorter courses of treatment based on findings from Part A.
MK-3682 (formerly IDX21437) Data Presentation at AASLD Annual Meeting
MK-3682 is an investigational oral prodrug HCV nucleotide analogue NS5B polymerase inhibitor. Phase 1/2a clinical trial results for MK-3682 are scheduled to be presented in a poster session (Abstract #1974) at The Liver Meeting®. HCV infected subjects (24 GT1 and 20 GT2/3) were randomized to receive placebo or 50, 150 or 300 mg of MK-3682 daily for seven days. Following initial pharmacokinetic and pharmacodynamic analysis, enrollment into the 50 mg and 150 mg treatment groups was discontinued due to a small reduction in viral load. In the 300 mg arms, the mean maximum viral load reductions from baseline for 7-day dosing were 4.6 and 4.1 log10 IU/mL in GT 2 (n=3) and GT 3 subjects (n=7), respectively. In GT1a (n=3) and GT1b subjects (n=5), the mean maximum viral load reductions from baseline for 7-day dosing were 4.8 and 3.9 log10 IU/mL respectively.
To date, no discontinuations due to an adverse event and no drug-related serious adverse events have been reported. Most adverse events were mild or moderate in intensity, with no apparent dose effect. There were no clinically significant abnormalities reported in routine blood and urine biomarker panels and physical examinations. Initial results from this study were previously announced by Idenix Pharmaceuticals in April 2014.
About Grazoprevir/Elbasvir
Grazoprevir/elbasvir (MK-5172/MK-8742, MK-5172A) is an investigational, oral, once-daily, fixed-dose combination chronic HCV treatment, consisting of grazoprevir, an investigational oral, once-daily HCV NS3/4A protease inhibitor, and elbasvir, an investigational oral, once-daily HCV NS5A replication complex inhibitor. In October 2013, Merck announced that the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation to grazoprevir/elbasvir for treatment of chronic HCV infection. Breakthrough therapy designation is intended to expedite the development and review of a candidate that is planned for use, alone or in combination, to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.
Merck’s Commitment to HCV
For nearly 30 years, Merck has been at the forefront of the response to the HCV epidemic. Merck employees are dedicated to applying their scientific expertise, resources and global reach to deliver innovative healthcare solutions that support people living with HCV worldwide.
About Merck
Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebook and YouTube.
Merck Forward-Looking Statement
This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of Merck’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.
Risks and uncertainties include, but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and healthcare legislation in the United States and internationally; global trends toward healthcare cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; Merck’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of Merck’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.
Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck’s 2013 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).
1 Defined as HCV RNA below the limit of quantification or below the limit of detection at the last visit on record – 4, 8, or 12 weeks after the completion of therapy.
Merck
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Pam Eisele, 267-305-3558
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Sarra Herzog, 201-669-6570
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Published: Nov 9, 2014
By Ed Susman , Contributing Writer, MedPage Today
Action Points
Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
BOSTON -- Patients with decompensated liver cirrhosis who were transferred from hospitals to a transplant center faced worse outcomes, researchers suggested here.
In a series of 99 patients transported from outlying hospitals to a liver transplant center, 10 were eligible for transplant, but only three of them underwent liver transplantation during their admission while seven others died, reported Chad Cornish, MD, of the University of Rochester in N.Y., and colleagues.
Cornish's group found that the mean length of stay at the outside hospital was 6.8 days, and the time of the request to transfer the patients and delivery of the patient to the tertiary care center took a mean of 1.2 days, according to their poster presentation at the America Association for the Study of Liver Diseases annual meeting.
Transfer delays were caused by lack of bed space at the tertiary center or because the patient was too unstable to transfer. However, Cornish said none of the patients in the single-center study experienced a transfer delay because of health insurance issues.
"These patients have underlying liver disease and they may decompensated due to encephalopathy -- change in mental status, a gastrointestinal bleed, ascites that are no longer under control. Anyone who is cirrhotic is a sick patient to begin with; they have some other insult and their condition tailspins from there," Cornish said.
"Sometimes we can stabilize them," he continued, "but sometimes the patient has spiraled so far out of control, there is little that can be accomplished. A lot of patients that are transferred to [the transplant center] -- mainly in hopes that a liver transplant would be possible -- do not do well."
Cornish and colleagues wanted to determine how well these transferred patients fared when sent to the tertiary facility.
"Tertiary care liver transplant centers frequently receive requests from outlying hospital to transfer patients with decompensated cirrhosis for a higher level of care, including evaluation for liver transplantation," they explained. "There have been no published studies looking at clinical outcomes for patients with acute decompensated cirrhosis who are transferred to a liver transplant center or barriers to the interhospital transfer."
The study population consisted of patients (ages 18 and up) transferred from an outlying hospital to the university's Strong Memorial Hospital (SMH) for management of acute decompensated cirrhosis between January 2011 and July 2013. They were identified through the hospital's transfer request logs.
Among 30 cases of interhospital transfer delay, 30% were due to lack of bed availability while 13% cases of delay were due to the patient being too unstable to transfer, the authors wrote.
Nearly one-third of the patients died during their initial admission after a mean length of stay while two additional patients died after being transferred on a separate occasion. Mean peak outside hospital Model for End-Stage Liver Disease (MELD) score for patients who died at SMH was 31.3.
His group concluded that "very few patients with acute decompensated cirrhosis transferred from an outlying hospital were suitable for liver transplantation and an even smaller number of patients were transplanted. A substantial number of patients died following a prolonged hospitalization. Given the limited resources and cost associated with transferring patients to a tertiary care liver transplant center, patient selection for transfer is crucial in order to provide optimal care and allocate researches appropriately."
They called for additional studies to identify risk factors that can help prioritize patient transfers.
In commenting of the presentation, Mohsen Hasanin, MD, from the University Alabama in Birmingham, told MedPage Today that "when we see patients from outside the hospital, they are pretty much gone. These patients need to be transferred earlier. By the time they are transferred from primary care or from the outpatient setting by gastroenterologists or hepatologists, they have very bad as outcomes as transplant."
Cornish and co-authors disclosed no relevant relationships with industry.
Hasanin disclosed no relevant relationships with industry.
Presented: Monday, November 10, 2014, 3:15 pm Eastern - Hynes Convention Center, Boston, MA
BOSTON, Nov. 9, 2014 /PRNewswire/ -- The newest and most effective drugs for the treatment of hepatitis C have a cure rate of up to 98 percent, but the cost of these therapies has been controversial. Accurately assessing the cost of treating all patients with HCV in the US has yet to be determined.
Part of the problem is getting an accurate count of the Americans with HCV as those with HCV are often asymptomatic and many are undiagnosed. The Centers for Disease Control and Prevention (CDC) has recommended a one-time age-based screening of all baby boomers (those born between 1945 and 1965). Risk-based screening was the standard protocol before the CDC's recent recommendation.
Researchers used a decision analytic Markov modeling approach to estimate the cost-effectiveness of screening and treating patients with HCV. They created a model based on five strategies of treatment and simulated patients until death:
They assumed treatment for fibrosis stages F2 to F4, a 98 percent cure rate, and the cost of the drugs at current prices. They assumed 1.2-1.4 million new patients would be diagnosed with HCV from age-based screening. Treatment effectiveness was measured in quality-adjusted life years, which assumes that patients with HCV would live their lives without HCV progressing to cirrhosis, decompensated liver disease, or liver transplantation. Different screening and treatment strategies were compared to each other based on the standard threshold for cost-effectiveness (incremental cost-effectiveness ratio or ICER) from a societal perspective.
The authors concluded that birth cohort screening followed by treating all HCV (+) patients was the most cost-effective strategy with ICERs well below the accepted threshold of $50,000 per quality adjusted years of life gained. The lead investigator, Zobair Younossi MD, MPH, FAASLD concluded that "screening and treating baby boomers with highly effective and well tolerated all oral anti-HCV regimens are highly cost-effective with great health and economic benefits at the population level." Dr. Younossi is Chairman of Medicine, Inova Fairfax Medical Campus and Vice President for Research, Inova Health system, Falls Church, Virginia.
Abstract title:
The use of all oral regimens for treatment of chronic hepatitis C (CHC) coupled with birth cohort screening is highly cost effective: The health and economic impact on the US population.
AASLD is the leading medical organization for advancing the science and practice of hepatology. Founded by physicians in 1950, AASLD's vision is to prevent and cure liver diseases. This year's Liver Meeting®, held in Boston, November 7-11, will bring together more than 9,000 researchers from 55 countries.
A pressroom will be available from November 7 at the annual meeting. For copies of abstracts and press releases, or to arrange researcher interviews, contact Gregory Bologna at 703-299-9766.
Press releases and all abstracts are available online at www.aasld.org.
Media Contact: Gregory Bologna
703-299-9766
gbologna@aasld.org
Press Room: November 7 – 11, 2014
Hynes Convention Center, Boston, MA
Telephone: 617-954-2977
Researcher: Zobair Younossi, MD
Email: zobair.younossi@inova.org
This release was issued through The Xpress Press News Service, merging e-mail and satellite distribution technologies to reach business analysts and media outlets worldwide. For more information, visit http://www.XpressPress.com.
SOURCE American Association for the Study of Liver Diseases (AASLD)
RELATED LINKS
http://www.aasld.org
Attention: Medical & Science Editors/Producers
Media Contact: Gregory Bologna
703-299-9766
gbologna@aasld.org
Press Room: November 7 – 11, 2014
Hynes Convention Center, Boston, MA
Telephone: 617-954-2977
Researcher: Heather Platt, MD
Email: hplatt@gmail.com
Phone: 732-485-9222
For Immediate Release
Presented: Date Monday, November 10
Liver transplantation is a therapeutic option for selected patients with liver cancer with high 5-year survival rates of 75 – 80 percent. HIV-infected patients often do not have access to liver transplantation, and experience with HIV-infected patients with liver cancer undergoing liver transplantation is limited.
An international group of researchers at 43 centers in North and South America, Europe, and Australia retrospectively identified 135 HIV-positive patients with hepatocellular carcinoma (HCC) who underwent potentially curative treatment. Twenty-seven patients who underwent orthotopic liver transplantation (OLT) were compared to 108 patients who underwent either radiofrequency ablation, surgical resection, or percutaneous ethanol injection.
Compared to the 108 patients undergoing other potentially curative therapy, the 27 patients undergoing OLT were younger, had higher Child-Turcotte-Pugh scores (used to assess liver function), and more often had multiple liver tumors, but were otherwise similar in disease etiology, frequency of alcohol abuse, and control of HIV infection.
Patients who had a liver transplantation had a significantly higher 5-year survival rate of 85 percent, compared to 52 percent for all other curative therapies combined. The 5-year survival rate of 85 percent was similar to 75 – 80 percent reported in HIV-negative patients with HCC undergoing OLT.
When asked about the results, Heather Platt, MD, principal investigator of the study said, "The primary point of this study is to show that HIV+ patients with HCC should be included in evaluation for OLT, as there does not seem to be any difference in survival when compared to HIV negative patients. Importantly, the survival data, while retrospective, does indicate a benefit compared to other curative interventions. "
Dr. Platt also addressed barriers to transplanting these patients. Dr. Platt said, "The main barriers include a center's experience and comfort with transplanting HIV+ patients. HIV+ patients are examined quite carefully for compliance and for anticipation of post-transplant complications. This requires a comprehensive, multidisciplinary transplant program including specialists in HIV care."
Abstract title:
Liver transplantation for HIV-infected patients with hepatocellular carcinoma (HCC)
###
AASLD is the leading medical organization for advancing the science and practice of hepatology. Founded by physicians in 1950, AASLD's vision is to prevent and cure liver diseases. This year's Liver Meeting®, held in Washington, November 7-11, will bring together more than 9,000 researchers from 55 countries.
A pressroom will be available from November 7 at the annual meeting. For copies of abstracts and press releases, or to arrange researcher interviews, contact Gregory Bologna at 703-299-9766.
Press releases and all abstracts are available online at www.aasld.org.
Attention: Medical & Science Editors/Producers
Media Contact: Gregory Bologna
703-299-9766
gbologna@aasld.org
Press Room: November 7 – 11, 2014
Hynes Convention Center, Boston, MA
Telephone: 617-954-2977
Researcher: Mary Ford, MS
Email: mford4@health.nyc.gov
Phone: 347-396-2419
For Immediate Release
Presented: Monday, November 10 2014
It is estimated that 2.4 percent of New York City (NYC) residents have HCV infection, but half do not know their status. To address this gap, the NYC Department of Health and Mental Hygiene launched the Check Hep C Program, which, in its first year, helped increase the rate of complete hepatitis C (HCV) diagnostic testing among at risk populations and has successfully linked more people to HCV supportive services, care, and treatment.
The Check Hep C program funded eight organizations at 12 community sites, including syringe exchange programs and community health centers. Over 4,500 people were screened and tested, and of those who tested HCV RNA positive, 85 percent attended their first medical appointment and 50 percent remained in care, which put them in the position to benefit from the HCV treatment advances of 2014. In describing the Check Hep C program, Mary Ford, MS, program evaluator for the program said, "The screening protocol for the Check Hep C program includes testing those in the birth cohort as well as those who are at high risk from injection drug use either currently or in the past."
After Centers for Disease Control and Prevention (CDC) recommended a one-time screening for HCV infection for all Americans born from 1945 to 1965 (baby boomers), New York State passed a law mandating that health care providers offer a HCV test to individuals in this age group, and provide care or linkage to care for those who test positive. However, many people at high risk for HCV were not visiting a health care provider to get tested or screened.
According to Ms. Ford, "While a formal evaluation of the mandate has not been completed as of yet, we have collected anecdotal evidence from many of our partners and from providers that we have met with during the year, finding that adherence varies widely -- lack of knowledge by primary care providers, lack of accountability by leadership, lack of adequate resources for testing, lack of integration between service delivery locations, etc."
In order to increase screening in groups at highest risk for HCV, the Program generated awareness about HCV and recruited patients through a local media campaign and targeted outreach. The program improved rates of complete diagnosis through field based rapid testing, and confirmation (RNA testing) immediately after HCV antibody positive tests.
In the Check Hep C program population, the estimated prevalence of HCV infection was 14 percent, and 9 percent among persons born after 1965 and 14 percent among baby boomers. Among enrollees, 25 percent had injected drugs in the past (20 times more likely to have HCV infection), 15 percent were homeless (1.6 times more likely to have HCV infection), and 18 percent had been previously incarcerated (5 times more likely to have HCV infection). In addition to supporting the birth cohort based screening recommendation of the CDC, the authors of the article recommend expanding the Check Hep C model to settings with high-risk populations.
"Further outreach and education to primary care providers will be needed to fully implement the testing mandate, and programs like Check Hep C will play an integral role this process in high-risk communities, said Ms. Ford. "The successful model demonstrated in Check Hep C can be replicated not only in community-based organizations, but also in community health centers, and outpatient clinics of large medical centers."
Abstract title:
Check Hep C: A community-based approach to hepatitis C diagnosis in high-risk populations
###
AASLD is the leading medical organization for advancing the science and practice of hepatology. Founded by physicians in 1950, AASLD's vision is to prevent and cure liver diseases. This year's Liver Meeting®, held in Boston, November 7-11, will bring together more than 9,000 researchers from 55 countries.
A pressroom will be available from November 7 at the annual meeting. For copies of abstracts and press releases, or to arrange researcher interviews, contact Gregory Bologna at 703-299-9766.
Press releases and all abstracts are available online at www.aasld.org.
PUBLIC RELEASE DATE: 9-Nov-2014
Contact: Paul Scotti
scotti.paul@mayo.edu
904-953-0199
Mayo Clinic
JACKSONVILLE, Fla. -- All patients with hepatitis C who receive a liver transplant will eventually infect their new livers. These transplanted organs then require anti-viral treatment before they become severely damaged. But traditional post-transplant hepatitis C therapy can take up to a year, is potentially toxic and can lead to organ rejection.
Now, at the American Association for the Study of Liver Diseases (The Liver Meeting® 2014) in Boston, researchers at Mayo Clinic report that use of two new oral medications post-transplant is safe and beneficial, and requires only 12 weeks of treatment.
"This is the first study to examine the use of these two new drugs -- simeprevir and sofosbuvir -- in liver transplant recipients, and, based on this large study, we find it to be a better option than current treatment," says the study's lead researcher, Surakit Pungpapong, M.D., a transplant hepatologist and an associate professor of medicine at Mayo Clinic in Florida.
Standard pre- and post-transplant treatment requires the use of interferon injections, along with ribavirin. Interferon engages the human immune system to fight the hepatitis C virus, but this immune response can also lead to organ rejection, Dr. Pungpapong says. Interferon can cause a variety of side effects, including anemia, depression, irritability, flu symptoms, insomnia, and hair loss, among others, he says.
Given the clinical importance of the study, results are being presented at the meeting in a plenary session.
Chronic hepatitis C virus is the most common chronic bloodborne infection in the United States, affecting more than 3 million individuals. Most infected people have no symptoms of the disease until liver damage from chronic inflammation occurs decades later -- which happens to 5-30 percent of infected individuals. Hepatitis C infection accounts for two-thirds of newly diagnosed chronic liver disease cases and 40 percent of liver transplants.
For this study, Mayo Clinic researchers enrolled post-transplant patients at their three sites, including Rochester, Minnesota, Scottsdale, Arizona and the Mayo Clinic Transplant Center in Jacksonville, Florida, which has one of the five most active liver transplants programs nationwide. Researchers will report on outcomes of more than 100 patients, but the study is still ongoing.
These patients were too sick to be treated for hepatitis C before their transplant, says Dr. Pungpapong. "By the time liver cirrhosis occurs, it could be too late to use anti-viral drugs," he says.
Simeprevir and sofosbuvir were approved for pretransplant use last year by the Food and Drug Administration (FDA), but not as a combined therapy. The FDA also required that they be combined with interferon and ribavirin.
But in a large clinical trial, researchers tested simeprevir and sofosbuvir without interferon -- an off-label use -- in pretransplantation patients and found the combination to be a brief and effective therapy. In this study, the Mayo researchers extended the idea of using these drugs together without interferon in post-transplantation patients.
The researchers found that eradication of the virus in the patients was excellent -- more effective than the use of interferon and ribavirin -- and with much fewer side effects. "We believe use of these drugs, both pre- and post-transplant represents a substantial clinical advance," Dr. Pungpapong says.
###
The study was funded in part by a Davenport grant from the Department of Transplant of Mayo Clinic in Jacksonville, Florida.
About Mayo Clinic
Recognizing 150 years of serving humanity in 2014, Mayo Clinic is a nonprofit worldwide leader in medical care, research and education for people from all walks of life. For more information, visit 150years.mayoclinic.org, MayoClinic.org or newsnetwork.mayoclinic.org.
MEDIA CONTACT: Paul Scotti, Mayo Clinic Public Affairs, 904-953-0199. Email: scotti.paul@mayo.edu
By Bill Berkrot
NEW YORK Sun Nov 9, 2014 6:37pm IST
(Reuters) - Now that new medicines promise to cure millions of hepatitis C patients in coming years, drugmakers including Gilead Sciences Inc are turning their attention to other liver diseases, with a potential market that could rival the success of statins, which generated more than $30 billion a year in sales at their peak.
Several companies are working on treatments for hepatitis B, which can be controlled but not yet cured, and for fatty liver conditions caused by rising obesity, which without treatment could affect half of all Americans by 2030, according to the American Liver Foundation (ALF). Some of the drugs will address advanced fibrosis and cirrhosis, which are the scarring that virtually all liver diseases cause without effective treatments. Each of these drugs, once approved, could reach annual sales of as much as $10 billion, industry analysts said.
Most of the treatments are now in early Phase I or Phase II clinical trials, with more informative interim data on several expected over the course of the next year.
Gilead, which was first to market with its hepatitis C cure Sovaldi late last year and has been racking up about $3 billion in sales each quarter, is a solid bet to be among the leaders in the next wave of liver therapies, experts said.
"The Gilead program is encouraging," said Dr. Naga Chalasani, director of gastroenterology and hepatology at Indiana University Hospital in Indianapolis, who is participating in clinical trials of promising drugs from Gilead and others.
Drugmakers are working to address the fatty liver disease known as NASH, or nonalcoholic steatohepatitis. Without treatment, NASH can progress to liver-destroying cirrhosis and potentially cancer.
ALF estimates that non-alcoholic fatty liver disease, including NASH, affects up to 30 percent of people in the United States. It can be caused by bad diets and alcohol abuse, and has also been tied to diabetes.
"We have no treatment for that condition other than tell a patient they need to lose weight," said Dr. Mauricio Lisker-Melman, director of the hepatology program at Washington University School of Medicine in St Louis.
Intercept Pharmaceuticals has attracted the most attention. Just released final data from a mid-stage clinical trial showed its obeticholic acid halted NASH progression and improved liver scarring in primarily moderately ill patients. "For now, no one else has demonstrated an antifibrotic effect in this population, and I believe we are ahead of the pack in that sense," said Intercept Chief Executive Mark Pruzanski.
Intercept plans to begin a Phase III trial with at least 1,000 more seriously ill patients next year.
Dr. Scott Friedman, dean for therapeutic discovery at Mt. Sinai Hospital in New York, who has worked with virtually all the companies in the field, said most were first testing drugs in patients whose liver damage is not advanced.
"Gilead has sort of leapfrogged that," Friedman said, tackling more serious damage, as its simtuzumab targets fibrotic scarring directly, rather than inflammation or other drivers of disease. Reversing cirrhosis and improving liver function is "the highest bar I can think of in this business, and it would be spectacular," he said.
Gilead faces competition from several smaller companies with promising drugs in development, including Intercept, France's Genfit, Israel's Galmed, Galectin Therapeutics, Conatus Pharmaceuticals and Raptor Pharmaceuticals, specialists said.
Gilead's antibody simtuzumab blocks an enzyme called LOXL2 that is directly involved in laying down bands of collagen that form the scar tissue behind cirrhosis. The collagen bands, which result from a wide variety of assaults on the liver, including alcohol and drug abuse, cross link haphazardly to destroy the liver's architecture and function.
Gilead expects to have a strong indication of whether its drug is working when one-year data from a two-year Phase II study becomes available next year.
"We have a very active research program," said Mani Subramanian, head of liver disease clinical research at Gilead. "We're targeting everything: metabolic issues, inflammation and fibrosis directly." He acknowledged challenges faced by drugmakers trying to address more advanced liver disease: "It's been a graveyard for drugs that try to reverse fibrosis," Subramanian said.
NOT FOR FAINT OF HEART
Chalasani at Indiana University Hospital estimated there may be 20 different drugs being tried by various drug companies that seem to be good targets.
But betting on them is not for the faint of heart. Intercept's shares shot from about $72 to over $400 in a matter of days in January after it was announced the trial of its drug would meet the intended goal. On the flip side, Galectin lost nearly two thirds of its value in July, when its NASH drug using a different approach had a setback in a Phase I trial.
Conatus is first testing its drug, emricasan, in patients facing acute liver failure, which has a 50 percent mortality rate in 28 days. Chief Executive Steven Mento said the goal was to "rescue these patients and prevent catastrophic organ failure." The company plans to work its way back, testing on less severely ill patients. The drug targets inflammation and excessive cell death seen as drivers of the disease.
Dr. David Bernstein, chief of hepatology at North Shore University Hospital in Manhasset, N.Y., called the Conatus drug exciting and the initial trial a sensible approach.
"There's limited downside because there's nothing else that can be done anyway," said Bernstein, who expects to be involved in future emricasan trials. "If you can reverse cirrhosis, you really will change the impact of liver disease worldwide."
Drugs that succeed in reversing cirrhosis "can be as big a class as the class of statins," said Conatus's Mento, referring to cholesterol drugs, such as Pfizer's Lipitor, which alone at its peak had annual sales of about $13 billion.
Raptor, by contrast, is developing a drug for NASH in children, a growing problem that has left liver specialists fearing an obese generation that could require liver transplants in the prime of life.
Raptor is testing a drug already approved for use in children for an extremely rare kidney disease. "In terms of safety, it's well established," said Raptor President and CEO designate Julie Anne Smith. It is now engaged in a year-long mid-stage trial of 169 children whose NASH was confirmed by liver biopsy with data expected in the first half of next year.
Companies are waiting for the U.S. Food and Drug Administration to outline what it will take to approve a NASH drug. "The FDA is struggling with what constitutes a meaningful improvement with a patient," Gilead's Subramanian said.
Goals such as reducing fat buildup or modestly improving fibrosis would likely be simpler and quicker to achieve, for example, than avoiding need for liver transplants.
The FDA is working "to identify clinically meaningful endpoints for NASH and related liver diseases to help guide drug development," it said in a statement.
The uncertainty from the FDA also creates risks for investors and has led some analysts to focus on other liver therapies. RBC Capital Markets analyst Michael Yee favors companies taking on hepatitis B, such as Arrowhead Research Corp, Canada's Tekmira Pharmaceuticals, Gilead and Isis Pharmaceuticals in partnership with GlaxoSmithKline. And one private company not to be ignored, OnCore Biopharma, founded by former Pharmasset executives, including the inventor of Gilead's Sovaldi.
While finding a cure for hepatitis B will not be easy, trials would mirror those for hepatitis C, with a simple blood test yielding clear results in months rather than years.
(Reporting by Bill Berkrot. Editing by Michele Gershberg and John Pickering)
