Sunday, November 9, 2014

November HCV Newsletters, AASLD Updates & Publications: SVR After Therapy Reduced Inflammation, Fibrosis in HCV Patients

This collection of newsletters is brought to you by a group of devoted advocates working hard to bring awareness and information to people affected by viral hepatitis.

We begin with updates from the liver meeting, held in Boston at the John B. Hynes Veterans Memorial Convention Center from Friday, November 7, through Tuesday, November 11. New research will be presented over the next couple of days which include fatty liver disease, complications of cirrhosis, hepatocellular carcinoma, and hepatitis C, with late-breaking data on interim results from ongoing interferon-free, ribavirin-free clinical trials.

AASLD In The News - Check Back For Updates
Updated Nov 10 - 9:00am

AASLD Index
Comprehensive data investigating HCV interferon-free, ribavirin-free regimens presented at the liver meeting is now available on the website.

Updated daily, categorized by genotype and pharmaceutical company, with links to breaking news, clinical data, commentary and slide-sets from premier Hepatitis C websites.

Hepatitis C New Drug Research: Conference Reports 

Advances for Practitioners - New Treatments for Hepatitis C - The Liver Meeting® 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.


Merck’s Four-Week Hepatitis C Regimen Fails to Top Gilead
Merck & Co. (MRK) won’t move forward with an ultra-short hepatitis C regimen that attempted to cut treatment durations in half by combining two of its drugs with another from Gilead Sciences Inc.
Patients in the mid-stage, 102-person trial got Merck’s experimental drugs grazoprevir and elbasvir, along with Gilead’s Sovaldi, for as little as four weeks, with the length of treatment based partly on how severe their infection was.

In patients whose livers weren’t already badly damaged by the virus, 38.7 percent were cured in four weeks and 86.7 percent were cured in six weeks, according to data to be presented at the American Association for the Study of Liver Diseases conference in Boston.

That’s well below the 90 percent-plus cure rates seen with longer treatments. Merck won’t take the four-week course into a new round of testing, said Eliav Barr, the company’s vice president of infectious diseases...

Reuters
Merck 4-week hep C regimen with Gilead's Sovaldi comes up short
Nov 9 (Reuters) - An attempt by Merck & Co to shorten hepatitis C treatment to just four weeks by adding Gilead Sciences Inc's huge selling Sovaldi to its own oral two-drug combination came nowhere near the desired efficacy due to a high rate of relapses, according to interim data from a midstage study.

Several companies have been working to find ways to further reduce the number of weeks of treatment needed, while keeping cure rates above 90 percent.

A just approved pill called Harvoni that combines Sovaldi with another Gilead drug requires eight weeks of treatment for many patients, and longer for tougher to treat patients.

In the ongoing Merck trial of previously untreated patients, only 38.7 percent had no detectable sign of the liver destroying virus after four weeks of treatment with Sovaldi and Merck's grazoprevir/elbasvir combination. Nineteen of the 31 patients in the four-week treatment arm relapsed prior to the planned end of the study, which is 12 weeks after completion of dosing.

The preliminary data was set to be presented on Monday at the American Association for the Study of Liver Diseases (AASLD) meeting in Boston.

The best result so far in the multi-arm, three-drug study called C-Swift was observed with eight weeks of treatment of patients with cirrhosis in which 94.7 percent had no detectable virus. They will be deemed cured if the virus has not reappeared 12 weeks after stopping treatment.

With a six-week regimen in non-cirrhotics, 86.7 percent of patients had no sign of virus up to 8 weeks after completing treatment, according to the interim results.

"These findings will inform the design of larger studies aimed at understanding the potential of short-duration triple therapy across multiple patient types," Dr. Eric Lawitz, the study's lead investigator, said in a statement.

The three drugs each work in a different way to help prevent the virus from replicating. But following failure of the 4-week experiment, Merck said it will turn its attention to studying a combination of three of its own drugs in development rather than involving the Gilead medicine in future studies.

The hepatitis C field has been moving at a lightning pace. Only a handful of years ago, patients needed 48 weeks of treatment with drugs that had harsh side effects and only cured about 40 percent of patients.

The new all-oral treatments eliminate the need for injectable interferon and its flu-like side effects, as well as another older drug called ribavirin that caused anemia and other problems, while dramatically increasing cure rates and reducing treatment duration.
 (Reporting by Bill Berkrot; Editing by Chris Reese)

Interim Data from Proof-of-Concept Study of Merck’s Investigational Hepatitis C Treatment Grazoprevir/Elbasvir in Combination with a Nucleotide Inhibitor (C-SWIFT study) Presented at The Liver Meeting®

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.
Table 1
Treatment
duration (weeks)
Treatment-Naïve
Cirrhotic
Treatment-Naïve
Non-Cirrhotic
8664
SVR4/818/19**
94.7%**
16/20
80%
26/30
86.7%
12/31
38.7%
Virologic Failure*14419
*All treatment failures were due to relapses.
**21 patients enrolled; two patients discontinued; 18/19 (modified intent-to-treat).
Data includes week 8 follow up data for 99/102 patients (excludes 2 cirrhotic patients who discontinued).
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.

Patients with decompensated liver cirrhosis who were transferred from hospitals to a transplant center faced worse outcomes, researchers suggested here.

AASLD 2014: Sustained Response to HCV Treatment Reduces Mortality, Liver Cancer, Liver Transplants
People who achieve sustained virological response (SVR) when treated with interferon-based therapy for hepatitis C have a lower risk of death, are less likely to develop liver cancer, and need fewer liver transplants than those who were treated but not cured, according to results from a meta-analysis of more than 34,000 patients presented at the American Association for the Study of Liver Diseases (AASLD) Liver Meeting this week in Boston.

Combination therapy offers quicker, less toxic eradication of hep C in liver transplant patients
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.

Mayo Clinic Study Reveals New Drugs to Treat Hepatitis C in Post Liver Transplant Patients
Surakit Pungpapong, M.D., transplant hepatologist and associate professor of medicine at Mayo Clinic in Florida, talks about his latest study, how two new oral medications, used post –liver transplant – are safe and beneficial in the treatment of Hepatitis C and require only 12 weeks of treatment instead of up to one year.

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.

“We were examining the impact of only the currently approved treatment for HCV in children—pegylated interferon (subcutaneous weekly injections by a caregiver) and oral ribavirin—on patients, caregivers, and families,” according to study co-author Rachel A. Annunziato, PhD, associate professor for clinical psychology, Fordham University, New York. “Results indicated that at baseline, caregivers were experiencing high levels of distress and family stress was elevated, while after treatment, family stress worsened.” According to Dr Annunziato, their results can have implications for other treatments that involve frequent invasive procedures to be administered by caregivers, as families may benefit from additional support when facing similar grueling treatment regimens.

What Does Social Media and Crowdsourcing Have to Do With Women and Liver Disease?
BOSTON, Nov. 8, 2014 /PRNewswire/ -- Autoimmune hepatitis is a chronic liver disease that is found more frequently in women than men. Researchers at Indiana University studied the environmental exposures possibly related to autoimmune hepatitis and reported their findings at the annual meeting of the American Association for the Study of Liver Diseases. "Interestingly, autoimmune hepatitis is quite far behind other autoimmune liver diseases in terms of environmental risk assessment," said Craig Lammert, MD, principal investigator on the study.

While the cost of novel hepatitis C drugs has been rigorously debated, real-world data on the safety and efficacy of these drugs has now started showing up. A white paper released by CVS Health Research Institute in September of this year reported that in addition to the downward trend in utilization of sofosbuvir, which has cure rates of more than 95%, high discontinuation rates are being observed. Overall discontinuation rates were around 8%, discontinuation rates among treatment-naïve patients were the highest at 8.7%, while patients who had been previously treated for hepatitis C, and presumably failed previous therapy, discontinued only 5.3% of the time.

While the cost of hepatitis C treatment continues to be a major topic of debate—with the approval of simeprevir (Olysio), sofosbuvir (Sovaldi), and now the combination, sofosbuvir and ledipasvir (Harvoni)—those in favor of the treatment provide a strong research-based argument. In a recent issue of Evidence-Based Immunology and Infectious Disease, we heard both sides of the discussion.1,2 Disease complications—cirrhosis, end-stage liver disease, hepatocellular carcinoma, and liver transplantation—cost the US healthcare system approximately $6.5 billion annually, expected to touch $9.1 billion by 2024.3 At $1000 per dose, sofosbuvir alone will cost $84,000 for the typical 12 weeks of therapy in the United States, while its combination with ledipasvir is estimated at $94,500

Are US Veterans Being Appropriately Tested and Treated for Hepatitis B?

AASLD- BMS Daclatasvir+sofosbuvir achieves SVR12 in 90% of treatment-naïve/ 86% of treatment-experienced geno 3 patients


On November 6, the FDA approved Olysio by Johnson & Johnson to be used in combination with Gilead's Sovaldi, as an all-oral, interferon- and ribavirin-free treatment option for genotype 1 chronic hepatitis C infection.

FDA Hepatitis Update: Changes to Olysio (simeprevir) label‏

SIMEPREVIR (GALEXOS) now covered by BC PharmaCare!

Sofosbuvir/ledipasvir effective for relapsed hep C patients
Patients with chronic hepatitis C genotype 1 infection who relapse after sofosbuvir plus ribavirin may be successfully retreated with sofosbuvir plus ledipasvir, a new study demonstrated

After hepatitis C cure, companies target next big liver disease market

AASLD Publication  

The Sunday issue of "The Liver Meeting Today" is now available.

Index
Sunday
Monday


Sunday Topics Include

Postgraduate course examines inflammation and steatohepatitis
The link between inflammation and steatohepatitis came under scrutiny during a Saturday session of the AASLD postgraduate course on the Clinical Implications of Inflammation and Immunity in...
Read more

Starzl Lecture Looks at Living Donor Liver Transplantation
The number of liver transplants from living donors in the United States still lags behind the number performed in other parts of the world, according to Jean C. Emond, MD, Vice Chair and Chi...
Read more

Endoscopy Course Covers GI Endoscopy for Cirrhotic Patients
More and more, gastrointestinal endoscopy is used routinely to screen and manage cirrhotic patients for common GI issues and to treat complications of advanced liver disease, such as varicea...
Read more

Liver Transplantation SIG Program Spotlights Successful Outreach Through Project ECHO
During Saturday’s special interest group half-day program on outreach in liver transplantation, three speakers described Project ECHO, a collaborative model of medical education and care man...
Read more

Read more @ The Liver Meeting Today

In addition Clinical Care Options (CCO) just launched an interactive learning activity presented by Paul Y. Kwo, MD., reviewing strategies for the management of cirrhosis in persons with HCV, including treatment with recently approved drugs and several new DAAs soon to be approved; HCV Treatment With New Therapies in Patients With Cirrhosis

Over at Healio the November issue of "HCV Next" is available with a look at a new study reporting decreased fibrosis scores in persons who achieved SVR using interferon-based therapy, an update on daclatasvir plus sofosbuvir regimen from the AASLD/EASL Special Conference, and HCV-associated non-Hodgkin’s lymphoma, highlights are provided below.

November HCV Newsletters & Publications 


New At Healio
Healio will be providing live coverage of this months "Liver Meeting."

VIDEO: New HCV era is 'exciting', but there is still 'work to do', expert says.

November 2014 print edition of HCV Next

"HCV Next" offers information on a range of topics, which include diagnosis, new combination therapies, side effects, drug/drug interaction, guidelines, fatty liver disease and more.

Table of Contents
COVER STORY
Prison Breakthrough

EDITORIAL
HCV/HIV Coinfection: Yesterday, Today and Tomorrow
Cody A Chastain, MD

THE TAKE HOME

Recent News
Depression, illness uncertainty evident in chronic HCV patients on watchful waiting
FDA approves simeprevir to be used with sofosbuvir for HCV genotype 1

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The HCV Advocate newsletter is a valuable resource designed to provide the hepatitis C community with monthly updates on events, clinical research, and education

In The November Issue:

Alan Franciscus, Editor-in-Chief
It was a slow second half of the month for HCV drug development. This is likely due to the upcoming American Association for the Study of Liver Diseases (AASLD)conference in Boston, MA in November. There was, however, some important news that I will recap in this month’s edition. Read more...

Lucinda K. Porter, RN
This month, Lucinda discusses Hepatitis C in Prisons. Few are more ignored than people with HCV who are in jails and prisons. However, the incarcerated were not ignored by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America, who assigned a high treatment priority to the incarcerated. 

The Origins of the Hepatitis C Virus
Alan Franciscus, Editor-in-Chief
Where did HCV come from? While I was reading about the history of Ebola, I started thinking again about the origins of hepatitis C. Did hepatitis C, like Ebola, jump species to humans? When a virus jumps from an animal to a human, it is called zoonotic. This is important information because if there is a reservoir in another species it could mean that we may not be able to eradicate the hepatitis C virus completely. 

Lucinda K. Porter, RN
Lucinda reviews studies on obesity and liver tissue aging, the relationship between HCV and increased heart size, the association between neurological problems at birth and the presence of maternal hepatitis B or hepatitis C, and liver injury from herbals and dietary supplements. 

Hepatitis C & U.S. Hispanics
Alan Franciscus, Editor-in-Chief
There are an estimated 40 million Hispanics living in the United States. Hispanics are the largest and fastest growing minority group in the U.S. By the year 2050, 25% of the U.S. population will be of Hispanic origin. The number of Hispanics with hepatitis C (2.6%) is higher than the number of people with hepatitis C in the general population (1.3%). 

Medicare to Cover One-Time Test for Baby Boomers
Alan Franciscus, Editor-in-Chief
Important information from the National Viral Hepatitis Roundtable: On June 2, 2014, the Centers for Medicare & Medicaid Services (CMS) announced that Medicare will cover hepatitis C testing at no cost to beneficiaries whom the U.S. Preventive Services Task Force recommends be screened. Specifically, Medicare will cover a one-time test for beneficiaries who are born from 1945 through 1965 and ongoing tests for those who are at risk.

Patient Assistance Programs
Alan Franciscus, Editor-in-Chief
Spread the word: The new drugs to treat hepatitis C are very expensive. If your insurance or Medicare/Medicaid does not cover the medications there are patient assistance programs that can cover all of the costs or the co-payments. Many people and medical providers are not aware of these programs. If you are in need of these programs or know of others who are please pass along this information.
Read more...

Weekly Special Topic:

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HBV Advocate: for accurate, timely and cutting-edge information on HBV treatment and vaccines.

HBV Journal Review

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Our newsletter is sent out for free electronically on the 1st of every month.
Our mission is to educate the general public about hepatitis C and to provide resources and support for those affected by the virus. Hep C Connection offers a helpline to answer your questions regarding hepatitis C (HCV). You can expect respect, patience & understanding, in clear, jargon-free language from our staff & volunteers. Call 1-800-522-HEPC (4372) today!

November Newsletter

In This Issue 
In This Issue Support Groups
New HCV Treatment
Accessing Treatment
Financial Resources for HCV
Treatment Articles of Interest
Upcoming Events Desserts & Delights Photos
Clinical Trials HCV
Patient Survey

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The primary goal of the Caring Ambassadors Program is to help individuals with challenging health conditions to become ambassadors for their own health. We are here to help you—that is now and always will be our singular focus.

November 2014 Literature Review
Monthly Pubmed Review of the most relevant research on HCV

Index
CLINICAL TRIALS, COHORT STUDIES, PILOT STUDIES 1-3
BASIC AND APPLIED SCIENCE, PRE-CLINICAL STUDIES 4-4
HIV/HCV COINFECTION 4-6
COMPLEMENTARY AND ALTERNATIVE MEDICINE 6-6
EPIDEMIOLOGY, DIAGNOSTICS & MISCELLANEOUS WORKS 6-14
LIVER CANCER 14-17

Caring Ambassadors is excited to announce the release of Hep C Discussion Point™.  Try this free powerful and interactive online tool for people living with hepatitis C !

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Hep is an award-winning print and online brand for people living with and affected by viral hepatitis. Offering unparalleled editorial excellence since 2010, Hep and HepMag.com are the go-to source for educational and social support for people living with hepatitis.

New In November 
You’re Cured! Now What?
You don't just end HCV treatment and wake up feeling like your old self, says John Rickman.

S/O Combo Good to Go
FDA finally approves Sovaldi and Olysio to treat hep C geno 1’s.

How people with hep C can find health insurance — or shop around for a better plan.


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HepCBC’s MONTHLY NEWSLETTER

The hepc.bull, has been “Canada’s hepatitis C journal” since the late 1990′s and has been published nonstop since 2001. The monthly newsletter contains the latest research results, government policy changes, activities and campaigns you can get involved in, articles by patients and caregivers, and a list of support groups plus other useful links.

November Newsletter Coming Soon......
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Liver Lowdown is the monthly general interest e-newsletter of the American Liver Foundation.

Newsletter
November Newsletter Coming Soon.....
October Edition

FEATURE: LIVER CANCER
This month we focus on liver cancer, which strikes 33,000 Americans each year. We welcome your thoughts and comments and invite you to share your experiences.

PATIENT PROFILE
Gretta Goodis knows how lucky she is. Five years ago, she was diagnosed with primary liver cancer (hepatocellular carcinoma). Today, she is cancer-free.


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GI & Hepatology News is the official newspaper of the AGA Institute and provides the gastroenterologist with timely and relevant news and commentary about clinical developments and about the impact of health-care policy. The newspaper is led by an internationally renowned board of editors.

November Newsletter Coming Soon......
View Current Issue (Vol. 8 No. 10 October 2014): PDF | Interactive Issue
Read breaking news stories now: visit the GI & Hepatology News website.

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The New York City Hepatitis C Task Force is a city-wide network of service providers and advocates concerned with hepatitis C and related issues. The groups come together to learn, share information and resources, network, and identify hepatitis C related needs in the community. Committees form to work on projects in order to meet needs identified by the community. 

November Newsletter Coming Soon.....
November 2014 NYC Hep ABC Newsletter
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Composite illustration of a couple dancing, a woman swimming, a scale, diary, and vegetables.Preventing Type 2 Diabetes Steps Toward a Healthier Life
Diabetes raises your risk for heart disease, blindness, amputations, and other serious issues. But the most common type of diabetes, called type 2 diabetes, can be prevented or delayed if you know what steps to take. 



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This monthly e-newsletter will provide health information and insight from Johns Hopkins experts. Each issue features information on common health topics and interests, health tips, patient stories, updates in medical research and clinical trials, upcoming events, a healthy recipe, and more.
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Advice for Fighting Flu This Season
With all the news about infectious diseases, people may get the idea that the flu isn’t all that serious. But we need to remember that it can be a very dangerous—even fatal—illness especially to the very young, the very old and the immune-compromised. Your best way to stay protected? Get the flu vaccine, and practice good hand hygiene to avoid transmitting it to others.
Learn more.

Podcast -  Infectious diseases
Week of November 10, 2014

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Hepatitis C and Flu Shots
By Lucinda K. Porter, RN
It's that time of year when each of us is confronted with a choice: should I get a flu shot? This decision is especially important to those living with a chronic condition, such as hepatitis C. Influenza, aka the "flu," affects an average of 5% to 20% of the United States' population. The flu is not just a bad cold - it is a potentially serious illness...

NPR
Flu Season Brings Stronger Vaccines And Revised Advice
November 06, 2014 5:20 PM ET
The symptoms of the flu are familiar: fever, chills, cough, congestion, feeling very, very tired. If you're a healthy adult under 65, you'll most likely recover in a week or two.

But for those older than 65, things can get worse fast, says Dr. H. Keipp Talbot, an infectious disease specialist at Vanderbilt University...
Transcript / Listen Here

CDC
Check out updates at the CDC for the current status or influenza in your state.
Weekly U.S. Influenza Surveillance Report

Stay well, see you all soon.
Tina

After hepatitis C cure, companies target next big liver disease market

After hepatitis C cure, companies target next big liver disease market

By Bill Berkrot

NEW YORK Sun Nov 9, 2014 8:07am EST
(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)

Saturday, November 8, 2014

Fight For Your Liver: Investment Commentary/ Why investors will be following the liver meeting

Investment Commentary
Meg Tirrell tells us which biotech companies investors will be watching ahead of an annual liver disease conference.


AASLD- BMS Daclatasvir+sofosbuvir achieves SVR12 in 90% of treatment-naïve/ 86% of treatment-experienced geno 3 patients

Daclatasvir+sofosbuvir regimen achieves SVR12 in 90% of treatment-naïve and 86% of treatment-experienced genotype 3 patients

ALLY-3 is the first Phase 3 study of an all-oral, ribavirin-free treatment regimen for genotype 3 HCV patients with a 12-week treatment duration

Genotype 3 is the second most common genotype worldwide and has emerged as one of the most difficult to treat

PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol-Myers Squibb Company (NYSE: BMY) today announced late-breaking data from the landmark ALLY Trial investigating a ribavirin-free 12-week regimen of daclatasvir (DCV) in combination with sofosbuvir (SOF) in genotype 3 hepatitis C (HCV) patients, a patient population that has emerged as one of the most difficult to treat. The results of the study, which showed sustained virologic response 12 weeks after treatment (SVR12) in 90% of treatment-naïve and 86% of treatment-experienced patients, will be presented at The Liver Meeting® 2014, the Annual Meeting of The American Association for the Study of Liver Diseases (AASLD), in Boston, MA, November 7 – 11.

“Both treatment naïve and treatment experienced patients in the ALLY-3 study achieved high SVR rates. These results are encouraging given that patients with genotype 3 have emerged as among the hardest to treat,” said David R. Nelson, M.D., Professor of Medicine, Molecular Genetics and Microbiology Director, UF Clinical and Translational Science Institute, and Assistant Vice President of Research for the University of Florida. “Genotype 3 is associated with a more rapid progression of disease and remains a challenge to the efficacy of even newer regimens. The ALLY-3 results demonstrate the possibility of bringing a cure to genotype 3 patients in an all-oral, 12-week regimen.”

These results build upon the existing body of data on the daclatasvir and sofosbuvir combination. Data from an open-label, randomized study of daclatasvir with sofosbuvir in genotypes 1, 2, and 3 demonstrated that the 24-week regimen of daclatasvir and sofosbuvir (± ribavirin) achieved SVR12 in 89% of patients with genotype 3. The ALLY study presented at The Liver Meeting investigates the regimen for 12 weeks, halving the previous treatment duration. Other ongoing ALLY studies examine diverse HCV populations across all genotypes: cirrhotic and post-liver transplant patients, as well as treatment-naïve and treatment-experienced patients who are co-infected with HIV.

“HCV is a complex disease, and the treatment community needs multiple options to address the remaining unmet medical needs,” said Douglas Manion, M.D., head of Specialty Development, Bristol-Myers Squibb. “Daclatasvir has shown pan-genotypic activity in bench research, a factor which is becoming increasingly important as we learn more about the complexity of HCV. Further, daclatasvir’s potential to be combined with many other agents, including sofosbuvir, is significant in continuing to develop additional treatment options that may help patients of all genotypes achieve cure.”

In the ALLY-3 study, the daclatasvir and sofosbuvir combination regimen was well tolerated, with no deaths, treatment-related serious adverse events, or discontinuations due to adverse events. The most frequent side effects (≥5%) were headache (19.7%), fatigue (19.1%), nausea (11.8%), diarrhea (8.6%), insomnia (5.9%), abdominal pain and arthralgia (both 5.3%). Additionally, there were 17 (11.2%) treatment failures, with 16 relapses post-treatment and 1 rebound at the end of treatment. There were no viral breakthroughs in this ribavirin-free regimen.

About ALLY-3: Study Design

This Phase 3 open-label clinical trial enrolled 152 genotype 3 HCV patients; 101 treatment-naïve patients and 51 treatment-experienced patients in 2 cohorts each received daclatasvir 60 mg and sofosbuvir 400 mg once daily for 12 weeks, with 24 weeks of follow-up. The primary endpoint was SVR12 rates, defined as HCV RNA < LLOQ target detected or not detected at follow-up week 12 in treatment-naïve and treatment-experienced patients.

The full abstract for the presentation is available at The Liver Meeting website.

About Hepatitis C

Hepatitis C is a virus that infects the liver and is transmitted through direct contact with infected blood and blood products. Approximately 170 million people worldwide are infected with hepatitis C, with an estimated 2.7–3.9 million chronically infected in the United States. Up to 90 percent of those infected with hepatitis C will not spontaneously clear the virus and will become chronically infected. According to the World Health Organization, up to 20 percent of people with chronic hepatitis C will develop cirrhosis; of those, up to 20 percent may progress to liver cancer.

About Genotype 3

Genotype 3 is estimated to affect 54.3 million people and is the second most common worldwide behind genotype 1 (83.4 million). It is now potentially the most difficult-to-treat genotype, and the more aggressive nature of genotype 3 lies in the damage it causes to the liver, as it is associated with progressive disease, increased rates of steatosis and a disproportionately increased risk of hepatocellular carcinoma.

About Bristol-Myers Squibb’s HCV Portfolio

Bristol-Myers Squibb’s research efforts are focused on advancing late-stage compounds to deliver the most value to patients with hepatitis C. At the core of our pipeline is daclatasvir, a potent pan-genotypic NS5A complex inhibitor (in vitro), which continues to be investigated in multiple treatment regimens and in people with co-morbidities.

Daklinza (daclatasvir) was recently approved in the EU for use in combination with other medicinal products across genotypes 1, 2, 3 and 4 for the treatment of chronic hepatitis C virus (HCV) infection in adults. Daklinza is also approved in Japan in combination with Sunvepra (asunaprevir), a NS3/4A protease inhibitor. The Daklinza+Sunvepra Dual Regimen is Japan’s first all-oral, interferon- and ribavirin-free treatment regimen for patients with genotype 1 chronic HCV infection, including those with compensated cirrhosis.

In 2013, Bristol-Myers Squibb’s investigational all-oral DCV-TRIO regimen (daclatasvir/asunaprevir/beclabuvir) received Breakthrough Therapy Designation in the U.S., which helped to expedite the start of the ongoing Phase 3 UNITY program. Study populations include non-cirrhotic naïve, cirrhotic naïve and previously treated patients. In addition to UNITY 1 and 2, both the UNITY-3 study among Japanese treatment-naïve and -experienced genotype 1 patients and UNITY-4, which studies the DCV-TRIO regimen without ribavirin in cirrhotic and non-cirrhotic patients in Korea, Russia and Taiwan, are currently ongoing. The DCV-TRIO regimen is being studied as a fixed-dose-combination treatment with twice daily dosing.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.

Bristol-Myers Squibb Forward Looking Statement

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that daclatasvir will receive regulatory approval in the United States, or if approved, that it will become a commercially successful product. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2013, in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.

AASLD-Achillion Reports 100% SVR12 in a Phase 2 Combination Study With ACH-3102 and Sofosbuvir

Achillion Reports 100% SVR12 in a Phase 2 Combination Study With ACH-3102 at the Liver Meeting 2014 (AASLD)

- Achillion Achieves 100% SVR12 in Eight-Week Phase 2 Trial Evaluating a Ribavirin-Free Regimen of ACH-3102 and Sofosbuvir for Genotype 1 HCV ("Proxy Study") Including Nine of 12 Patients With Viral Loads Higher Than 6 Milachlion IU/ml at Baseline –

- Reports Additional Preclinical Results for ACH-3422, Uridine-Analog Nucleotide NS5B Polymerase Inhibitor –

NEW HAVEN, Conn., Nov. 8, 2014 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today announced the presentation of results from the ongoing Phase 2 study of ACH-3102 in a late breaker poster and data in three preclinical posters on ACH-3422. The poster presentations are being made at the 65th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), The Liver Meeting 2014, which takes place through November 11, 2014 in Boston, MA.

Late Breaker Poster Presentation: Phase 2 pilot study evaluating eight week treatment of ACH-3102 in combination with sofosbuvir for genotype 1 treatment-naïve HCV
In a late breaker poster presentation, Achillion reported updated interim results from an ongoing interferon-free, ribavirin-free, Phase 2 open-label, randomized, partial-crossover study to evaluate the efficacy, safety, and tolerability of eight weeks or six weeks of ACH-3102 and sofosbuvir, a marketed nucleotide polymerase inhibitor, without ribavirin, in treatment-naïve genotype 1 HCV-infected patients. The primary objective of the study is determination of sustained viral response 12 weeks (SVR12) after the completion of therapy. Eighteen patients were enrolled, including six observational patients. Twelve patients completed eight weeks of treatment consisting of 50 mg of ACH-3102 and 400 mg of sofosbuvir administered once daily while observational patients received no drug during this phase of the trial.

Of the 12 patients treated, 100 percent (n=12/12) achieved SVR12. Of the 12 patients treated in this study, nine of 12 patients had a baseline viral load substantially greater than 6 million IU/ml at baseline. No on-treatment viral breakthrough or post-treatment viral relapse has been observed.

Preclinical poster presentations on ACH-3422
Achillion presented three posters at AASLD which reported updated preclinical results on ACH-3422. The in vitro results demonstrated that this nucleotide pro-drug has improved potency against genotype 3 HCV as compared to sofosbuvir. In addition, in a separate poster presentation, Achillion reported that ACH-3422 displays additive to synergistic activity when combined with ACH-3102 or sovaprevir, Achillion's Phase 2 NS3/4A protease inhibitor, in vitro. Furthermore, the high barrier to resistance for ACH-3422 was supported with the ability of the agent to block, in vitro, the appearance of resistant colonies in combination with other direct-acting antiviral agents.

"The antiviral activity and safety profile observed to date for ACH-3422 both in preclinical studies and in the ongoing 422-001 Phase 1 trial support further development with this nucleotide in combination with Achillion's other direct-acting antivirals, and represents an exciting treatment option for HCV," commented Professor Edward Gane, M.D., Deputy Director and Hepatologist, New Zealand Liver Transplant Unit, Auckland City Hospital in New Zealand, and Lead Investigator in the ACH-3422 Phase 1 proof-of-concept study and Phase 2 proxy study of ACH-3102 and sofosbuvir.
Reprints of the posters are available on the Company's website at www.achillion.com/resources.

About HCV
The hepatitis C virus is the most common cause of viral hepatitis, which is an inflammation of the liver. It is currently estimated that more than 150 million people are infected with HCV worldwide including more than 5 million people in the United States. Three-fourths of the HCV patient population is undiagnosed; it is a silent epidemic and a major global health threat. Chronic hepatitis, if left untreated, can lead to permanent liver damage that can result in the development of liver cancer, liver failure or death.

About Achillion Pharmaceuticals
Achillion is seeking to apply its expertise in biology and structure-guided design and a deep understanding of patient and clinician needs to develop innovative treatment solutions aimed at improving patients' lives. The company's scientific excellence, integrated capabilities and experienced team position it to successfully achieve its goal of advancing new products along the entire continuum from the bench to the patient. Achillion's pipeline is currently focused on small molecule therapeutics for infectious disease and complement-related diseases. www.achillion.com

Cautionary Note Regarding Forward-Looking Statements
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other important factors that could cause actual results to differ materially from those indicated by such forward-looking statements, including statements with respect to: the Company's reiteration that it remains on track to initiate all-oral ribavirin-free regimens with ACH-3422, ACH-3102 and sovaprevir for the treatment of HCV in 2015; the Company's expectations that the Phase 1 study of ACH-3422 could inform the potential initiation of combination studies of ACH-3422 and ACH-3102; and the Company's expectations that it may report preliminary results from its Phase 1 program during the fall of 2014. Achillion may use words such as "expect," "anticipate," "project," "intend," "plan," "aim," "believe," "seek," " estimate," "can," "focus," "will," and "may" and similar expressions to identify such forward-looking statements. Among the important factors that could cause actual results to differ materially from those indicated by such forward-looking statements are risks relating to, among other things Achillion's ability to: demonstrate in any current and future clinical trials the requisite safety, efficacy and combinability of its drug candidates; advance the preclinical and clinical development of its drug candidates, including ACH-3422, ACH-3102 and sovaprevir, under the timelines it projects in current and future clinical trials; obtain and maintain necessary regulatory approvals; obtain and maintain patent protection for its drug candidates and the freedom to operate under third party intellectual property; establish commercial manufacturing arrangements; identify, enter into and maintain collaboration agreements with appropriate third-parties; compete successfully with other companies that are seeking to develop improved therapies for the treatment of HCV; manage expenses; manage litigation; raise the substantial additional capital needed to achieve its business objectives; and successfully execute on its business strategies. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the year ended December 31, 2013, and its subsequent SEC filings.
In addition, any forward-looking statement in this press release represents Achillion's views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. Achillion disclaims any duty to update any forward-looking statement, except as required by applicable law.

Company Contact: Glenn Schulman Achillion Pharmaceuticals, Inc. Tel. (203) 624-7000 Media: Laurie Masonson Ogilvy PR Tel. (917)459-6164 Investors: Mary Kay Fenton Achillion Pharmaceuticals, Inc. Tel. (203) 624-7000 Investors: Tricia Truehart The Trout Group, LLC Tel. (646) 378-2953

AASLD-BMS Daclatasvir TRIO achieves 98% cure rate in treatment-naïve and 93% cure rate in treatment-experienced geno 1 patients w-cirrhosis when used with ribavirin

Phase 3 UNITY Trials Demonstrate High Cure Rates for Investigational, All-Oral Daclatasvir TRIO Fixed-Dose Combination in Genotype 1 Hepatitis C Patients, Including Those with Cirrhosis

Daclatasvir TRIO achieves 98% cure rate in treatment-naïve and 93% cure rate in treatment-experienced genotype 1 patients with cirrhosis when used with ribavirin, as shown in UNITY 2
12-week, all-oral treatment halves current regimen duration for hard-to-manage treatment-experienced genotype 1 patients with cirrhosis
Fixed-dose regimen also demonstrates 91% SVR rates in non-cirrhotic genotype 1 patients without requiring use of ribavirin


PRINCETON, N.J.--()--Bristol-Myers Squibb Company (NYSE:BMY) today announced late-breaking data from the UNITY Trial program investigating a 12-week regimen of its all-oral daclatasvir (DCV) TRIO regimen – a fixed-dose combination of daclatasvir with asunaprevir (ASV) and beclabuvir (BCV) – in a broad range of patients with genotype 1 hepatitis C virus (HCV).

The data will be presented at The Liver Meeting® 2014, the Annual Meeting of The American Association for the Study of Liver Diseases (AASLD), in Boston, MA, November 7 – 11. The primary endpoint for both studies was the percentage of patients who achieved cure, defined as HCV RNA<LLOQ TD/TND at post-treatment week 12 for treatment-naïve and treatment-experienced patients.
“Even with the most recent HCV treatment advances, genotype 1 patients with cirrhosis remain difficult to treat”
The UNITY-2 study, which evaluated cirrhotic patients in a 12-week regimen of the DCV-TRIO, showed sustained virologic response 12 weeks after treatment (SVR12) among 98% of treatment-naïve and 93% of treatment-experienced cirrhotic patients with ribavirin (RBV) and 93% of treatment-naïve and 87% of treatment-experienced cirrhotic patients without ribavirin.
“Even with the most recent HCV treatment advances, genotype 1 patients with cirrhosis remain difficult to treat,” said Andrew J. Muir, M.D., MHS, Associate Professor of Medicine; Clinical Director, Gastroenterology & Transplant Hepatology, Duke Gastroenterology. “Currently, treatment-experienced cirrhotic patients still require a 24-week regimen to achieve high SVR rates. The data from this clinical trial using the DCV-TRIO regimen showed high cure rates for this population in a 12-week regimen, and has the potential to aid treatment adherence and provide a shorter treatment duration to achieve cure.”

Study Design and Results
The Phase 3 UNITY clinical trial program is an ongoing study investigating 12-week regimens of the DCV-TRIO fixed-dose combination (daclatasvir 30 mg plus asunaprevir 200 mg plus beclabuvir 75 mg) in non-cirrhotic and cirrhotic genotype 1 patients.

The open-label UNITY-1 study evaluated a 12-week regimen of the DCV-TRIO without ribavirin in treatment-naïve and -experienced non-cirrhotic patients. Non-cirrhotic treatment-naïve patients (n=312) and treatment-experienced patients (n=103) received the DCV-TRIO fixed-dose combination in one pill twice daily for 12 weeks, with 24 weeks of follow-up. The majority of the patients (73%) were genotype 1a, and 91% of all patients achieved SVR12. 92% of treatment-naive patients and 89% of treatment-experienced patients achieved cure, without the use of ribavirin.

In the UNITY-2 study, both cirrhotic treatment-naïve and treatment-experienced patients received the DCV-TRIO fixed-dose combination, one arm without ribavirin (n=102) and one with ribavirin (n=100). The study was double-blinded to ribavirin, and the majority of the patients (74%) were genotype 1a. The study showed 96% of all patients who received the DCV-TRIO with ribavirin achieved SVR12, and 90% of those who received the DCV-TRIO without ribavirin achieved SVR12.
“The Phase 3 UNITY results for the daclatasvir TRIO fixed-dose combination are particularly compelling for genotype 1 patients with cirrhosis, whose treatment is often harder to manage than non-cirrhotic patients,” said Douglas Manion, M.D., head of Specialty Development, Bristol-Myers Squibb. “BMS continues to recognize that HCV is an extremely complicated disease with no ‘one-size-fits-all’ treatment solution, and the UNITY results are especially promising for serving patients with cirrhosis, a specific but significant portion of genotype 1 patients.”

In both UNITY-1 and UNITY-2 there were low rates of adverse events (AEs) leading to discontinuation and of serious adverse events (SAEs) overall. In UNITY-1 there were 7 SAEs, all considered not related to study treatment, and 3 AEs leading to treatment discontinuation. The most common AEs were headache (25.8%) and fatigue (16.6%). In UNITY-2, there were 3 SAEs related to treatment and 4 AEs leading to discontinuation. The most common AEs were headache and fatigue (both 19.8%).
Full abstracts for both presentations are available at The Liver Meeting website.

About Hepatitis C
Hepatitis C is a virus that infects the liver and is transmitted through direct contact with infected blood and blood products. Approximately 170 million people worldwide are infected with hepatitis C, with an estimated 2.7–3.9 million chronically infected in the United States. Up to 90 percent of those infected with hepatitis C will not spontaneously clear the virus and will become chronically infected. According to the World Health Organization, up to 20 percent of people with chronic hepatitis C will develop cirrhosis; of those, up to 20 percent may progress to liver cancer.

About Bristol-Myers Squibb’s HCV Portfolio
Bristol-Myers Squibb’s research efforts are focused on advancing late-stage compounds to deliver the most value to patients with hepatitis C. At the core of our pipeline is daclatasvir, a potent pan-genotypic NS5A complex inhibitor (in vitro), which continues to be investigated in multiple treatment regimens and in people with co-morbidities.

Daklinza (daclatasvir) was recently approved in the EU for use in combination with other medicinal products across genotypes 1, 2, 3 and 4 for the treatment of chronic hepatitis C virus (HCV) infection in adults. Daklinza is also approved in Japan in combination with Sunvepra (asunaprevir), a NS3/4A protease inhibitor. The Daklinza+Sunvepra Dual Regimen is Japan’s first all-oral, interferon- and ribavirin-free treatment regimen for patients with genotype 1 chronic HCV infection, including those with compensated cirrhosis.

In 2013, Bristol-Myers Squibb’s investigational all-oral DCV-TRIO regimen (daclatasvir/asunaprevir/beclabuvir) received Breakthrough Therapy Designation in the U.S., which helped to expedite the start of the ongoing Phase 3 UNITY program. Study populations include non-cirrhotic naïve, cirrhotic naïve and previously treated patients. In addition to UNITY 1 and 2, both the UNITY-3 study among Japanese treatment-naïve and -experienced genotype 1 patients and UNITY-4, which studies the DCV-TRIO regimen without ribavirin in cirrhotic and non-cirrhotic patients in Korea, Russia and Taiwan, are currently ongoing. The DCV-TRIO regimen is being studied as a fixed-dose-combination treatment with twice daily dosing.

Additional studies with daclatasvir in combination with sofosbuvir are being conducted in high unmet need patients, such as pre- and post-transplant patients, HIV/HCV co-infected patients and patients with genotype 3 as part of the ongoing Phase 3 ALLY Program.

About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.

Bristol-Myers Squibb Forward Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that daclatasvir or asunaprevir or any other compounds mentioned in this release will receive regulatory approval in the United States, or if approved, that they will become commercially successful products. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2013, in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.

Bristol-Myers Squibb Company
Media:
Carrie Fernandez, Office: 609-419-5448
Cell: 215-859-2605
carrie.fernandez@bms.com
or
Investors:
Ranya Dajani, 609-252-5330
ranya.dajani@bms.com
or
Ryan Asay, 609-252-5020
ryan.asay@bms.com

JANSSEN HIGHLIGHTS ITS HEPATITIS C CLINICAL DEVELOPMENT IN ADVANCE OF AASLD

Related - FDA approves simeprevir-sofosbuvir combo for hepatitis C
November 5, 2014 - Janssen Therapeutics, Division of Janssen Products, LP (Janssen) announced the U.S. Food and Drug Administration (FDA) has approved OLYSIO® (simeprevir), a hepatitis C virus (HCV) NS3/4A protease inhibitor, in combination with sofosbuvir as an all-oral, interferon- and ribavirin-free treatment option for genotype 1 chronic hepatitis C (CHC) infection in adult patients as part of a combination antiviral treatment regimen. Sofosbuvir is an HCV nucleotide analog NS5B polymerase inhibitor developed by Gilead Sciences, Inc.

Janssen Highlights its Hepatitis C Clinical Development Program in Advance of 2014 American Association for the Study of Liver Diseases (AASLD) Annual Meeting

BOSTON, Nov. 7, 2014 /PRNewswire/ -- Janssen R&D Ireland (Janssen) highlights its hepatitis C (HCV) clinical development program in advance of The Liver Meeting®, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), being held November 7-11, 2014 in Boston, Massachusetts.

Given the size, complexity and diversity of the HCV patient population, physicians will continue to need multiple treatment options and combinations in order to offer patients an opportunity for cure into the next decade.

The Janssen HCV clinical development program includes studies that investigate the use of simeprevir in several interferon-free regimens using selected combinations of direct-acting antivirals with different mechanisms of action targeting diverse patient populations. These studies are focused on potentially offering alternative and more immediate treatment options for physicians and patients where there is a high unmet need today or anticipated in the near future. Ongoing clinical studies include:
  • Phase 3 OPTIMIST studies examining the safety and efficacy of simeprevir and the nucleotide analog NS5B polymerase inhibitor sofosbuvir without interferon or ribavirin for the treatment of chronic HCV infection for treatment-naïve and treatment-experienced patients with and without cirrhosis.
  • Phase 2 IMPACT study evaluating the efficacy, safety and pharmacokinetics of simeprevir administered once daily in combination with sofosbuvir and the NS5A replication complex inhibitor daclatasvir in treatment-naïve and treatment-experienced patients with HCV genotype 1 and 4 infection and decompensated liver disease.
With the closing of the acquisition of Alios Biopharma, Inc. earlier today, Janssen now holds a platform of nucleotide analog polymerase inhibitors, the early-clinical stage compounds AL-335 and AL-516.

"Janssen is committed to combating hepatitis C by exploring the potential to bring forth, in a timely manner, an in-house interferon-free combination regimen to make a difference in patients' lives," said Gaston Picchio, Ph.D., Hepatitis disease area leader, Janssen.

About Hepatitis C

Hepatitis C, a blood-borne infectious disease of the liver and a leading cause of chronic liver disease, is a major global public health concern. Approximately 170 million people are infected with hepatitis C worldwide and 350,000 people per year die from the disease globally. When left untreated, hepatitis C can cause significant damage to the liver including cirrhosis. Additionally, hepatitis C may increase the risk of developing complications from cirrhosis, which may include liver failure.

About Janssen Pharmaceutical Companies of Johnson & Johnson

At Janssen, we are dedicated to addressing and solving some of the most important unmet medical needs of our time in oncology, immunology, neuroscience, infectious diseases and vaccines, and cardiovascular and metabolic diseases. Driven by our commitment to patients, we develop innovative products, services and healthcare solutions to help people throughout the world. Janssen R&D Ireland is part of the Janssen Pharmaceutical Companies of Johnson & Johnson. Please visit http://www.janssenrnd.com for more information.

IMPORTANT SAFETY INFORMATION

What is the most important information I should know about OLYSIO®?
  • If you are pregnant, or plan to become pregnant, talk with your healthcare provider before taking OLYSIO®. It is not known if OLYSIO® will harm your unborn baby. Also read the Medication Guides for peginterferon alfa (Peg-IFN-alfa) and ribavirin (RBV) if your healthcare provider prescribes these medications for you in combination with OLYSIO®.
    • Females must use an effective form of birth control during treatment with OLYSIO®. Talk with your healthcare provider about birth control methods that you may use during treatment with OLYSIO®.
  • OLYSIO® combination treatment may cause rashes and skin reactions to sunlight. These rashes and skin reactions to sunlight can be severe and you may need to be treated in a hospital. Rashes and skin reactions to sunlight are most common during the first 4 weeks of treatment, but can happen at any time during combination treatment with OLYSIO®.
    • Use sunscreen, and wear a hat, sunglasses, and protective clothing when you will be exposed to sunlight during treatment with OLYSIO®.
    • Limit sunlight exposure during treatment with OLYSIO®.
    • Avoid use of tanning beds, sunlamps, or other types of light therapy during treatment with OLYSIO®.
    • Call your healthcare provider right away if you get any of the following symptoms:
      • burning, redness, swelling or blisters on your skin
      • mouth sores or ulcers
      • red or inflamed eyes, like "pink eye" (conjunctivitis)
  • You should not take OLYSIO® alone. OLYSIO® should be used together with other medicines to treat chronic hepatitis C infection.
What should I tell my healthcare provider before taking OLYSIO®?

Before taking OLYSIO®, tell your healthcare provider if you:
  • have liver problems other than hepatitis C virus infection
  • have ever taken any medicine to treat hepatitis C virus infection
  • had a liver transplant
  • are receiving phototherapy
  • have any other medical condition
  • are of East Asian descent
  • are breastfeeding. It is not known if OLYSIO® passes into your breast milk. You and your healthcare provider should decide if you will take OLYSIO® or breastfeed. You should not do both.
  • Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
  • OLYSIO® and other medicines may affect each other. This can cause you to have too much or not enough OLYSIO® or other medicines in your body, which may affect the way OLYSIO® or your other medicines work, or may cause side effects. Do not start taking a new medicine without telling your healthcare provider or pharmacist.
  • Especially tell your healthcare provider if you take any of the following medicines (when taken by mouth or given by injection, where applicable): amiodarone (Cordarone®, Pacerone®), amlodipine (Norvasc®), atazanavir (Reyataz®), atorvastatin (Lipitor®, Caduet®), carbamazepine (Carbatrol®, Epitol®, Equetro®, Tegretol®), cisapride (Propulsid®, Propulsid Quicksolv®), clarithromycin (Biaxin®, Prevpac®), cobicistat-containing medicine (Stribild®), cyclosporine (Gengraf®, Neoral®, Sandimmune®), darunavir (Prezista®), delavirdine mesylate (Rescriptor®), dexamethasone, digoxin (Lanoxin®), diltiazem (Cardizem®, Dilacor XR®, Tiazac®), disopyramide (Norpace®), efavirenz (Sustiva®, Atripla®), erythromycin (E.E.S.®, Eryc®, Ery‑Tab®, Erythrocin®, Erythrocin Stearate®), etravirine (Intelence®), felodipine (Plendil®), flecainide (Tambocor®), fluconazole (Diflucan®), fosamprenavir (Lexiva®), indinavir (Crixivan®), itraconazole (Sporanox®, Onmel®), ketoconazole (Nizoral®), lopinavir (Kaletra®), lovastatin (Advicor®, Altoprev®, Mevacor®), mexiletine (Mexitil®), midazolam, milk thistle (Silybum marianum) or products containing milk thistle, nelfinavir (Viracept®), nevirapine (Viramune®, Viramune XR®), nicardipine (Cardene®), nifedipine (Adalat CC®, Afeditab CR®, Procardia®), nisoldipine (Sular®), oxcarbazepine (Oxtellar XRTM,Trileptal®), phenobarbital (Luminal®), phenytoin (Dilantin®, Phenytek®), pitavastatin (Livalo®), posaconazole (Noxafil®), pravastatin (Pravachol®), propafenone (Rythmol SR®), quinidine (Nuedexta®, Duraquin®, Quinaglute®), rifabutin (Mycobutin®), rifampin (Rifadin®, Rifamate®, Rifater®, Rimactane®), rifapentine (Priftin®), ritonavir (Norvir®), rosuvastatin (Crestor®), saquinavir mesylate (Invirase®), sildenafil (Revatio®, Viagra®), simvastatin (Zocor®, Vytorin®, Simcor®), sirolimus (Rapamune®), St. John's wort (Hypericum perforatum) or products containing St. John's wort, tadalafil (Adcirca®, Cialis®), telithromycin (Ketek®), tipranavir (Aptivus®), triazolam (Halcion®), verapamil (Calan®, Covera‑HS®, Isoptin®, Tarka®), voriconazole (Vfend®).
  • This is not a complete list of medicines that could interact with OLYSIO®. Ask your healthcare provider or pharmacist if you are not sure if your medicine is one that is listed above.
  • Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine.
What are the possible side effects of OLYSIO®?
  • The most common side effects in combination with Peg-IFN-alfa and RBV are skin rash, itching and nausea.
  • The most common side effects in combination with sofosbuvir are tiredness, headache and nausea.
  • Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of OLYSIO®. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1‑800‑FDA‑1088.
When taking OLYSIO® in combination with Peg-IFN-alfa and RBV, you should also read those Medication Guides. When taking OLYSIO® in combination with sofosbuvir, you should also read its Patient Information leaflet.

Friday, November 7, 2014

AASLD: HCV Not Main Attraction Anymore

Meeting Coverage

AASLD: HCV Not Main Attraction Anymore
Published: Nov 6, 2014
By Michael Smith, North American Correspondent, MedPage Today

As the therapeutic picture for hepatitis C begins to settle down, the volume of abstracts on the topic is plateauing at the annual meeting of the American Association for the Study of Liver Diseases (AASLD).
That's not to say that new HCV therapies won't get a lot of play, according to Gary Davis, MD, president of MedLogician Consulting of Ponte Vedra Beach, Fla., and secretary of the liver association.

But, he told MedPage Today in advance of the meeting, "there's a big shift toward fatty liver disease ... that reflects what people are seeing in the clinics."

Over the past several years, direct-acting HCV medications have stolen the show, with a host of new drugs and drug combinations working through the clinical trials process.
Now, with many of those drugs approved and others in the home stretch, meeting participants will be getting mature data, he said.

For instance, the meeting will get an update on the research that underpinned the recent approval of Gilead's ledipasvir/sofosbuvir combination, trade-named Harvoni.

And, Davis said, they can look forward to seeing the data that AbbVie is using to support its multidrug combination -- dubbed 3D -- which is now under review at the FDA.
"It's going to be pretty exciting to see where that's at," he said.

Gilead famously unleashed a firestorm of debate when it priced sofosbuvir (Sovaldi) at $1 a pill and Davis said participants might take all the drug-makers to task over pricing of HCV drugs.
"I'm anxious to hear the audience questions on this, what with the whole controversy over pricing," he said.

The picture in fatty liver disease is less clear than in HCV, but the condition is increasingly prevalent and researchers are now turning their attention to it, looking at the basic mechanisms as well as drug therapy.

It's a "hot area," he said.
Among the hot topics this year:
  • The role of bariatric surgery in non-alcoholic steatohepatitis.
  • Prednisone and pentoxifylline in alcoholic hepatitis
  • Combinations of direct-acting HCV agents post-transplant.
  • A recombinant enzyme in liposomal acid lipase deficiency.
Davis also said that there is increased interest in possible curative options for hepatitis B, an area of research that has been "stuck in the mud for years." HBV is tricky to cure, because the virus integrates itself into host cells and -- rather like HIV -- therapy has aimed at suppressing the virus rather than getting rid of it.

But several new compounds in the early stages of investigation aim to change that and the "HBV people are quite excited about it," Davis said.

As well, he said, participants will get results from a major trial of terlipressin, a drug for hepatorenal syndrome that is approved in several countries but not the U.S.

An initial report from the so-called REVERSE study -- of terlipressin plus albumin versus albumin alone -- will attract considerable interest, Davis said, since improvement in renal function in patients with the syndrome is correlated with improved survival.

Source