EASL 2015: Part 2 —Alan Franciscus, Editor-in-Chief

In part 2 of our European Association for the Study of the Liver (EASL) coverage I will wrap up with a brief overview of some of the remaining data. 

AbbVie:  Ombitasvir/Paritaprevir/Ritonavir for Treatment of HCV Genotype 1b In Japanese Patients with or without Cirrhosis: Results from Gift-I –K Chayama et al

In this current study, Japanese patients were treated with AbbVie’s 2D (paritaprevir/ritonavir plus ombitasvir) given once-a-day for 12 weeks.  This is different from the 3D regime given in the United States and elsewhere because Japanese patients metabolize AbbVie’s drugs differently.  With the 2D combinations Japanese patients reach high enough levels even without ribavirin or dasabuvir.    

In the study there were 215 HCV genotype 1b patients who received the study drugs, 42% were cirrhotic, and 35% were treatment experienced.  The overall cure rate was 95%.  The cure rates among those who had never been treated, as well as those who were treated previously (cirrhotic and non-cirrhotic) were all similar.  The most common side effects were headache, edema and sore throat. 

Comments:  Japan has a long history of hepatitis C.  AbbVie’s 2D combination will be a welcome addition to the drugs in Japan to treat Japanese patients.  For more information about HCV in Japan check out our HCV in Japan—HCV Around the World series.

 

NHANES:  Advanced Fibrosis is Common in Individuals whose Hepatitis C Has Not Been Diagnosed: Results from the National Health and Nutrition Examination Survey 2001-2012—P Udompap et al

This study has been reported at previous conferences, but it is worth discussing again.  The National Health and Nutrition Examination Survey (NHANES) used data from a group of 62,000 American adults of whom 45,000 were tested for hepatitis C antibodies—591 tested antibody positive and of those 420 were HCV RNA or viral load positive. 

Of the 420 who had chronic hepatitis C, 1 in 10 had cirrhosis and 1 in 5 had advanced fibrosis.  Approximately 50% did not know that they had hepatitis C. 

Comments:  This validates the recommendation for “Baby Boomer” testing.  This should WAKE UP the complacency among physicians and associations and start testing baby boomers NOW.  We want to test, monitor, treat, cure and save lives.

 

Gilead:  Ledipasvir/sofosbuvir treatment results in high SVR rates in patients with chronic genotype 4 and 5 HCV infection— A Abergel et al

A total of 44 HCV genotype 4 patients and 41 HCV genotype 5 patients were treated with the combination of sofosbuvir and ledipasvir for 12 weeks.  In both of the groups the patients were evenly divided between treatment experienced (TE) and those who had never been treated (TN) and those with and without cirrhosis (C & w/o C).  The cure rates in the HCV genotype 4 patients was TN =96% (21 of 22 pts); TE = 91% (20 of 22 pts); C= 100% (10 of 10 pts); w/o C = 91% (31 of 34 pts).  The most common side effects were fatigue and headache.

 

Comments:  These are very good cure rates with few side effects.  While the population of genotype 4 and 5 in the United States is very low—genotype 4 is very high in Egypt and other parts of the world (see HCV in Egypt in our HCV Around the World series).  Genotype 5 is primarily seen in South Africa and parts of Europe.  I will be writing an article on Genotype 5 for the June Mid-Monthly edition so stay-tuned.

 

Merck: The Phase 3 C-Edge Treatment-Naive (TN) Study of a 12-Week Oral Regimen of Grazoprevir (GZR, MK-5172)/Elbasvir (EBR, MK-8742) in Patients with Chronic HCV Genotype (Gt) 1, 4, or 6 Infection—S Zeuzem et al

This was a phase 3 study of a one pill, once-a-day grazoprevir and elbasvir pill taken for 12 weeks.  The study included treatment naïve (TN). The trial included a total of 421 infected HCV genotype 1, 4 or 6.  Most of the trial participants were male sex, and White.  Ninety-one percent were genotype 1.   Approximately 22% had cirrhosis. 

The overall cure rate was 95%: 92% for genotype 1a and 99% for genotype 1b; 100% (36 of 36 pts) of the genotype 4 patients were cured; 80% (5 of 6 pts) of genotype 6 patients were cured.  The most common side effects were headache, fatigue, nausea and joint pain.

 
Comments:  These are high cure rates with a low side effect profile and it will make a good addition to the treatment landscape of HCV in 2016.  In people with the genotype 1a NS5A resistance-associated variants (RAVs) it shows greater than a 5-fold loss in sensitivity to elbasvir (a protease inhibitor).  What this means in clinical practice in unknown at this time.

http://hcvadvocate.org/news/newsLetter/2015/advocate0615.html#1

HCV Advocate Eblast: May 15, 2015

Home	News				comments	email
May 15, 2015
Click here to view the eblast in the new format
Basics Clinical Trials Events Fact Sheets HBV Newly Diagnosed Treatment
EASL 2015: Snapshots by Alan Franciscus, Editor-in-Chief This year’s conference had many outstanding presentations about hepatitis C drugs in development—too many to cover in one edition of the HCV Advocate newsletter.  As a result, we will be covering EASL in this edition as well in the next Mid-Monthly edition.  I have tried to pick out a couple of most interesting studies from the presentations from AbbVie, BMS, Gilead, and Merck.			Disability & Benefits: Planning for Disability Programs by Jacques Chambers, CLU Even though there are some wonderful, new medications on the market, some people with HCV will still need to consider going on disability at some time in the future. For most people, it is not always easy to know when the right time to leave is. Liver disease caused by HCV is often marked by a gradual progression toward disability. As well, the emotional issues involved around leaving work and "becoming disabled" further cloud the decision-making process.
The Five: May Is Hepatitis Awareness Month by Alan Franciscus, Editor-in-Chief May is Hepatitis Awareness month. In this month's column, I will provide a brief overview of the five hepatitis viruses—prevalence, how they are transmitted, and how to prevent transmission. Important Note: This is a very brief overview of viral hepatitis. For detailed information about viral hepatitis see our Viral Hepatitis: The Basics.			What's New!: Viral Hepatitis—The Basics by Alan Franciscus, Editor-in-Chief In this guide I will discuss the basics of hepatitis A, B, and C, with a bit of information on D and E that will help us to understand the similarities and differences between these viruses that all affect the liver.
ReTweet This			Share This on Facebook
**To unsubscribe from the eblast, or to change your email address, click this button and send a message. To subscribe to Daily News Updates click here
Copyright © 2015 - HCV Advocate · All Rights Reserved

Hepatitis C: Drug Prices, Lack of Testing are Challenges

The tougher challenge, discussed at a closing day session led by the World Health Organization is finding a way to step up testing.  “Treating patients is not difficult; finding them is,” Peck said, "You can't treat what you haven't found."

Despite the wealth of choices physicians have in finding drugs to treat hepatitis C infection, two challenges remain in eradicating the disease—drug price and lack of global screening for the virus.
“Price is solvable,” said Markus Peck, MD, the outgoing secretary of the European Society for the Study of the Liver (EASL) interviewed at the International Liver Congress in Vienna, Austria.
“Pharma has to make some money on these drugs,” Peck said, since their cost of developing them has been high, “but as there is more competition we are quite sure the price will go down.”

There are currently 7 different classifications of drugs that fight hepatitis C. Those are nucleoside and nucleotide NS5B polymerase inhibitors, nucleoside analogs, protease inhibitors, nucleoside analogs, pegylated interferon, NS5A inhibitors, non-nucleoside NS5B inhibitors, and combination drugs that draw on two or more of those classes.

Not counting interferon, there are also 7 drugs or drug combos approved by the US Food and Drug Administration and another 14 in phase 3 drug trials.

 - See more at: http://www.hcplive.com/conference-coverage/easl-2015/Hepatitis-C-Price-Lack-of-Testing-are-Challenges#sthash.ggeNy7xf.dpuf

EASL 2015: Alcohol use disorders – stronger predictor of mortality than chronic hepatitis C virus infection

Chronic hepatitis C infection is associated with increased risk of mortality when severe comorbidities and/or alcohol use disorders are also present

April 25, 2015, Vienna, Austria: Results presented today at The International Liver Congress™ 2015, show that alcohol use disorders (AUD) have a serious, negative prognostic outcome with higher mortality risks in the general population and patients with hepatitis C virus (HCV) infection in particular.

The study found that chronic HCV infection has a limited impact on mortality, unless the patient also has other severe comorbidities, such as HIV infection, cancer or chronic kidney disease. In contrast, those with AUDs are at significant risk of death with a higher mortality risk observed across all the study subgroups.

Michaël Schwarzinger, Director, THEN (Translational Health Economics Network) and Vincent Mallet, Professor of Hepatology, Université Paris Descartes and Assistance Publique – Hôpitaux de Paris, France, commented: "There is an epidemiological relationship between chronic HCV infection and AUD. However, the burden of chronic HCV infection analyses barely take into account the potential confounding role of AUD on prognosis. Our primary aim was to study the confounding role of severe comorbidities and AUD on prognosis in Hep C patients in a real-life setting."

Between 2008 and 2012, 28,953,755 adults residing in Metropolitan France were hospitalised and 1,506,453 died at hospital. All hospitalised patients were characterised by severe comorbidities and their trajectory was tracked according to chronic HCV infection and/or AUD. Chronic HCV infection was present in 112,146 (0.39%) of hospitalised patients, AUD in 705,259 (2.44%), and both chronic HCV infection and AUD in 23,351 (i.e., 20.8% AUD recorded in Hep C patients).

The researchers found that:

• Chronic HCV infection was mostly associated with higher mortality risks in the presence of severe comorbidities (e.g., HIV/AIDS, liver transplant receipt)
• In the absence of severe comorbidities, the prognostic value of chronic HCV infection was mostly explained by the presence of AUD (end-stage liver disease and mortality)
• More broadly, AUD was associated with higher mortality risks in all hospitalized patients, and alcohol withdrawal or abstinence was significantly associated with lower mortality risks

"These results show that alcohol use disorders are a much more accurate indicator of mortality in chronic HCV infection, and highlight the need to encourage alcohol withdrawal and abstinence in all patients," said Professor Tom Hemming Karlsen, Scientific Committee Member, European Association for the Study of the Liver.

###

About The International Liver Congress™
This annual congress is the biggest event in the EASL calendar, attracting scientific and medical experts from around the world to learn about the latest in liver research. Specialists share research studies and findings, and discuss the hottest topics related to liver disease. This year, the congress is expected to attract approximately 10,000 delegates from all corners of the globe. 2015 is a very special year for EASL and the hepatology community as they will celebrate the 50th annual meeting. The International Liver Congress™ takes place from April 22-26, 2015, Vienna, Austria.

About EASL
Since EASL's foundation in 1966, this not-for-profit organisation has grown to over 4,000 members from more than 100 countries around the world. EASL is the leading liver association in Europe, it attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.

Contact
For more information, please contact the ILC Press Office at:
ilc.press@easloffice.eu or
+44 (0)20 3580 5444

General session 3, Hall D Presentation time: 09:45-10:00 Presenter: Michaël Schwarzinger (France)

Abstract G16:THE COUNFOUNDING ROLE OF SEVERE COMORBIDITIES AND ALCOHOL USE DISORDERS ON PROGNOSIS IN CHRONIC HEPATITIS C VIRUS INFECTION: AN ANALYSIS OF THE 2008-2012 FRENCH NATIONAL HOSPITAL DISCHARGE DATABASE
Michaël Schwarzinger* 1, Sophie Thiébaut2, Vincent Mallet3, Jürgen Rehm4 1THEN (Translational Health Economics Network), Paris, Canada, 2THEN (Translational Health Economics Network), 3Hepatology, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, France, 4Social and Epidemiological Research (SER) Department, Centre for Addiction and Mental Health, Toronto, Canada

Background and Aims: There is an epidemiological relationship between chronic hepatitis C virus (HCV) infection and alcohol use disorders (AUD). AUD is a leading cause of liver disease and death. However, burden of chronic HCV infection analyses barely take into account the potential confounding role of AUD on prognosis. Our aim was to compare the prognostic value of chronic HCV infection and AUD in the general population.

Methods: In 2008-2012, 28,953,755 adult individuals residing in Metropolitan France were hospitalized and 1,506,453 died at hospital (51.6% and 55.7% of National Vital Statistics, respectively). We characterized all hospitalized patients by severe comorbidities (see Table), and tracked their trajectory according to chronic HCV infection and/or AUD (including withdrawal/abstinence). Age at death was analyzed in multivariate Cox proportional hazards model from January 2008 to last discharge or transplantation with stratification by gender, main French regions, and having received care in teaching hospitals.

Results: Chronic HCV infection was present in 112,146 (0.39%) of hospitalized patients, AUD in 705,259 (2.44%), both chronic HCV infection and AUD in 23,351(0.08%; i.e., 20.8% of HCV and 3.3% of AUD). Overall, the adjusted hazard ratio of in-hospital death (aHR) was 1.90 (95% confidence interval 1.86-1.94), for chronic HCV infection and 3.13 (3.10-3.15) for AUD, with a negative interaction effect between chronic HCV infection and AUD (aHR, 0.93; 0.90-0.97). Alcohol withdrawal or abstinence was significantly associated with lower mortality risks (HR, 0.66; 0.65-0.67). Subgroup analyses by severe comorbidities revealed that chronic HCV infection was only associated with higher mortality risks in presence of severe comorbidities (Table: groups 1 to 4, and 7 to 12). In absence of severe comorbidities, the prognostic value of chronic HCV infection at all liver disease stages was either not statistically significant among patients with cirrhosis and milder liver disease stage (groups 13 to 17). In contrast, AUD was associated with higher mortality risks in all prognostic subgroups, including all liver disease stages.

Conclusions: AUD has a dismal prognostic value in the general population and in the minority group of patients with chronic HCV infection. Alcohol withdrawal and abstinence increase survival regardless of HCV treatment.

Disclosure of Interest: None Declared

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Source:  http://www.eurekalert.org/pub_releases/2015-04/eaft-aud042415.php

EASL 2015: ALLY-1 Trial Results Show Investigational Daclatasvir-Based Regimen Cures 94% of Post-Liver Transplant Patients with Hepatitis C and Up to 94% of Hepatitis C Patients with Cirrhosis (Child-Pugh Class A or B)

• 97% of post-transplant patients with HCV genotype 1a achieved cure
• 91% of post-transplant patients with HCV genotype 3 achieved cure  
• No need seen to alter existing transplantation medication regimens

Saturday, April 25, 2015 10:00 am EDT

(PRINCETON, N.J., APRIL 25, 2015) – Bristol-Myers Squibb Company (NYSE:BMY) today announced that primary endpoints were successfully met in ALLY-1, a Phase III clinical trial evaluating a 12-week regimen of daclatasvir and sofosbuvir once-daily with ribavirin for the treatment of patients with chronic hepatitis C virus (HCV) with either advanced cirrhosis or post-liver transplant recurrence of HCV. The data was presented as a late-breaker at The International Liver Congress™ 2015, the 50^th annual meeting of the European Association for the Study of the Liver (EASL) in Vienna, Austria from April 22-26.

“The results of the ALLY-1 trial point to the potential of this investigational daclatasvir-based regimen in a patient population with high unmet needs despite recent advances in hepatitis C treatment,” said Fred Poordad, M.D., ALLY-1 Lead Investigator and Clinical Professor of Medicine, Chief, Hepatology, University of Texas Health Science Center and VP, Academic and Clinical Affairs Texas Liver Institute. “Transplant patients take a variety of immunosuppressive medications to prevent organ rejection; that complicates the treatment of hepatitis C. In ALLY-1, we saw no drug-drug interactions between transplant and hepatitis C therapies and no need to make dose adjustments to patients’ transplant-related drugs while they received the daclatasvir-based regimen that resulted in high SVR12 rates.”

The study’s primary endpoints were reached, with 95% of post-transplant genotype 1 patients and 82% of genotype 1 patients with advanced cirrhosis achieving SVR12. Among all ALLY-1 patients, 94% of those with post-transplant HCV recurrence and 83% of all participants with advanced cirrhosis achieved cure (sustained virologic response 12 weeks after treatment; SVR12).

The Child-Pugh scoring system is commonly used to assess the severity and prognosis of chronic liver disease and cirrhosis, and uses an A through C classification (C being the most advanced) to categorize disease progression. Patients with class C cirrhosis are decompensated, often with later-stage conditions such as ascites (the build-up of fluid in the abdomen), hepatic encephalopathy (confusion or altered level of consciousness due to the liver’s inability to remove toxins from the blood), and abnormal liver function, which can complicate treatment. The ALLY-1 trial included 16 patients with decompensated cirrhosis Child-Pugh class C; nine (56%) achieved SVR12.

Over the course of the study, four advanced cirrhotic patients received a liver transplant during treatment; 3 of 4 extended treatment post-transplant (see study design below), and all 4 achieved SVR12.

In the study, there were no serious adverse events related to study medications throughout the treatment phase. The most common adverse events (≥10%) were headache (15%, 36%), fatigue (18%, 28%), anemia (20%, 19%), diarrhea (8%, 19%), nausea (17%, 6%), and arthralgia (2%, 13%) in the advanced cirrhotic and post-transplant cohorts, respectively. One patient discontinued therapy after 31 days due to headache, but still achieved SVR12. Nine patients in the cirrhosis cohort relapsed post-treatment, and one had detectable HCV RNA at the end of treatment; there were no on-treatment virologic breakthroughs. Three patients (genotypes 1a, 1b, 3) in the post-transplantation cohort relapsed. All 12 patients with relapse are being retreated with daclatasvir and sofosbuvir with ribavirin for 24 weeks.

 HCV is the leading indication for liver transplantation worldwide. Without treatment, HCV infection of the new liver after transplant is inevitable, and is associated with rapid progression to cirrhosis and death in up to 30% of patients within 5 years. The ALLY-1 study is the third study to report out of the Phase III ALLY program, which evaluates daclatasvir in combination with sofosbuvir in multiple high-unmet need patient populations and is at the center of Bristol-Myers Squibb’s HCV research focus. The ALLY-2 and ALLY-3 studies have previously been presented at the 2015 Conference for Retroviral and Opportunistic Infections and the 2014 American Association for the Study of the Liver’s The Liver Meeting, respectively, and subanalyses from each study with the ribavirin-free regimen of daclatasvir and sofosbuvir were presented as posters during EASL 2015.

Additionally, EASL issued 2015 Hepatitis C treatment guidelines that include a regimen of daclatasvir+sofosbuvir as the first 12-week treatment for patients with genotype-3 virus. The EASL guidelines now list daclatasvir+sofosbuvir regimens as options for treating all HCV genotypes and for use with patients coinfected with HCV/HIV. (Guidelines available here.)

Other Bristol-Myers Squibb presentations at The International Liver Congress included data from compassionate use programs in the EU that add to the real-world clinical evidence informing the use of daclatasvir-based regimens to treat patients with HCV conditions posing high unmet medical needs.

“The ALLY-1 trial results build off the ALLY-2 and ALLY-3 studies by demonstrating the versatility of the daclatasvir-based regimen to provide HCV cure in multiple patient populations that have been historically hard to manage, such as HCV genotype 3 patients, HIV/HCV coinfected patients, and patients with decompensated cirrhosis,” said Douglas Manion, M.D., Head of Specialty Development, Bristol-Myers Squibb. “Post-liver transplant and cirrhotic patients represent a still-unmet need and continue to present challenges to currently available regimens.”

About ALLY-1: Study Design
This Phase III open-label clinical trial enrolled treatment-naïve and treatment-experienced patients with HCV infection of any genotype in 2 cohorts: advanced cirrhosis (n=60) and post-liver transplant with HCV recurrence (n=53). All patients received daclatasvir 60 mg plus sofosbuvir 400 mg once-daily with ribavirin initially dosed at 600 mg/d (with potential for adjustment based on hemoglobin levels and creatinine clearance) for 12 weeks. Patients receiving a variety of immunosuppressive agents were permitted. In the cirrhosis cohort, patients transplanted during treatment could receive 12 weeks of extended treatment immediately post-transplant, regardless of treatment duration before transplant. The primary endpoint was the SVR12 rate (defined as HCV RNA <LLOQ (25 IU/mL) at post-treatment week 12) among genotype 1 patients in each cohort.

Read complete press release here....

EASL 2015: Statin use in HCV patients may lower risk of death, decompensation

VIENNA — Statin use in patients with hepatitis C virus and compensated cirrhosis seems to offer a protective effect against death and decompensation, according to a study presented at the 2015 International Liver Congress.

 “In compensated HCV cirrhosis, statin users have a significantly lower incidence of decompensation and better overall survival compared to statin non-users,” Arpan Mohanty, MD, from Yale School of Medicine, New Haven, Conn., said during her presentation. “Risk of decompensation and death was reduced by over 40%.”

In this retrospective cohort study, Mohanty and colleagues used the U.S. Department of Veterans HCV Clinical Case Registry, and by doing so, she said all patients would have had an equal opportunity to receive statins. 

Read more...

EASL 2015: Use of direct-antiviral agents helps overcome hepatitis C recurrence in liver transplant patients

New data presented today at The International Liver Congress 2015, supports the use of sofosbuvir (SOF)- and daclatasvir (DCV)-based regimens in patients with recurrence of the hepatitis C virus (HCV) following liver transplantation (LT). The results are based on data from patients with HCV being treated with second-generation DAAs in the large French prospective ANRS CO23 CUPILT study. Among them, 296 patients were treated with a combination of SOF+DCV, with or without ribavirin.

SOF- and DCV-based regimens offered high rates of sustained virologic response (SVR) coupled with good tolerance. The presented results focus on 130 patients who achieved SVR12; end of treatment therapy and SVR12 rates are 98% and 96%, respectively.

"The use of interferon-free regimens using DAAs has dramatically improved the management of liver transplant patients infected with HCV. The outstanding efficacy and safety results that sofosbuvir- and daclatasvir-based regimens demonstrated in patients with recurrent hepatitis C are impressive and will help us identify optimal treatment strategies using these new therapies," said Audrey Coilly, MD, Paul Brousse Hospital, Villejuif.

Read more....

EASL 2015: Hepatitis C screening essential to help catch patients with advanced liver fibrosis

Research validates the current recommendation that screening for hepatitis C, particularly among high-risk groups, is vital.

April 25, 2015, Vienna, Austria: Study results presented today at The International Liver Congress™ 2015 show that the occurrence of advanced liver fibrosis is similar for patients infected with the hepatitis C virus (HCV), whether or not they have been diagnosed.

Most individuals with HCV remain asymptomatic, which makes the diagnosis difficult. The study authors used the hypothesis that individuals whose HCV is not diagnosed are less likely to have advanced fibrosis than those who have been diagnosed. They then compared liver fibrosis between respondents of the National Health and Nutrition Examination Survey (NHANES) in the USA, in patients with diagnosed and undiagnosed HCV infection.

Of the respondents with known HCV infection, the proportion with a high, intermediate and low probability of advanced fibrosis was 14.5%, 40.3%, 45.2%, respectively; in those with undiagnosed HCV the results were 19.1%, 30.9%, 50.0%, respectively.

The study highlights that even if people are unaware they are infected with HCV, the virus affects their liver in the same way, resulting in advanced fibrosis. These results validate the current recommendation that screening for HCV, particularly among high-risk groups, is vital.

Read complete press release here....

EASL 2015: Cancer rates among patients with hepatitis C are increased compared to those not infected

New results show that cancer rates in patients with the hepatitis C virus (HCV) were significantly increased compared to the non-HCV cohort. The researchers suggest an extrahepatic manifestation of HCV may be an increased risk of cancer. 

Results recently announced at The International Liver CongressTM 2015 show that cancer rates in patients with the hepatitis C virus (HCV) were significantly increased compared to the non-HCV cohort. The researchers suggest an extrahepatic manifestation of HCV may be an increased risk of cancer. When all cancers are considered the rate is 2.5 times higher in the HCV cohort; when liver cancers are excluded, the rate is still almost 2 times higher.

The aim of the study was to describe the rates of all cancers in the cohort of HCV patients compared to the non-HCV population. Known cancer types associated with hepatitis C include non-Hodgkin's lymphoma, renal and prostate cancers, as well as liver cancer.

A retrospective study at Kaiser Permanente, Southern California, USA, was conducted. The study authors recorded all cancer diagnoses in patients over 18 years of age with or without HCV during 2008-2012. Within the timeframe of the study 145,210 patient years were included in the HCV cohort, and 13,948,826 patient years were included in the non-HCV cohort.

Read more...

Merck’s Pivotal Phase 3 C-EDGE Program Evaluating Grazoprevir/Elbasvir Shows High Sustained Virologic Responses Across Broad Range of Patients with Chronic Hepatitis C Virus Infection

• Data Sets Include Treatment-Naïve, Treatment-Experienced and HIV Co-Infected Patients with Chronic Hepatitis C Virus Genotypes 1, 4 or 6 Infection
• Merck Remains on Track to Submit New Drug Application (NDA) to U.S. Food and Drug Administration (FDA) in First Half of 2015

 VIENNA--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the first presentations of data from the company’s ongoing C-EDGE pivotal Phase 3 clinical trial program evaluating the investigational once-daily tablet grazoprevir/elbasvir (100mg/50mg) in patients with or without cirrhosis who are infected with chronic hepatitis C virus (HCV) genotypes 1, 4 or 6 (GT1, 4 or 6).1 Patients in both the HCV infected, treatment-naïve (C-EDGE TN), and HIV/HCV co-infected, treatment-naïve (C-EDGE CO-INFXN) trials treated for 12 weeks achieved rates of sustained virologic response 12 weeks after the completion of treatment (SVR12) of 95 percent (299/316 and 207/218, respectively). In addition, HCV infected, treatment-experienced patients (C-EDGE TE) treated with or without ribavirin (RBV) for 12 weeks achieved SVR12 rates of 94 percent (98/104) and 92 percent (97/105), respectively, and those treated for 16 weeks achieved SVR12 rates of 97 percent (103/106) and 92 percent (97/105), respectively. These data were presented at The International Liver CongressTM 2015 – the 50th annual congress of the European Association for the Study of the Liver (Abstract #G07, E-Poster P0886 and E-Poster P0887). A paper detailing the findings of C-EDGE TN was published online in the Annals of Internal Medicine today.

“Patients with co-morbidities and varying treatment experiences represent important segments of the chronic hepatitis C population in need of additional innovative treatment options,” said Dr. Eric Lawitz, vice president, scientific and research development, The Texas Liver Institute and clinical professor of medicine, The University of Texas Health Science Center, San Antonio. “These findings are important because they demonstrate that a single pill of grazoprevir/elbasvir taken once-daily achieved consistently high rates of SVR12 in the patient populations studied.”

Summary of SVR12 findings: C-EDGE TN, C-EDGE CO-INFXN, C-EDGE TE

C-EDGE TN

C-EDGE CO-INFXN

C-EDGE TE

Without RBV (n=316)

Without RBV (n=218)

Without RBV (n=105)

With RBV (n=104)

Without RBV (n=105)

With RBV (n=106)

Duration

12 weeks

12 weeks

12 weeks

12 weeks

16 weeks

16 weeks

All Patients:

95%

95%

92%

94%

92%

97%

SVR12

(299/316)

(207/218)

(97/105)

(98/104)

(97/105)

(103/106)

Cirrhotic

97%

100%

89%

89%

92%

100%

(68/70)

(35/35)

(33/37)

(31/35)

(35/38)

(37/37)

Non-cirrhotic

94%

94%

94%

97%

93%

96%

(231/246)

(172/183)

(64/68)

(67/69)

(62/67)

(66/69)

Genotype 1a

92%

94%

90%

93%

94%

95%

(144/157)

(136/144)

(55/61)

(56/60)

(45/48)

(55/58)

Genotype 1b or

other Genotype

99%

96%

100%

97%

96%

100%

1

(129/131)

(43/45)

(35/35)

(28/29)

(46/48)

(38/38)

Genotype 4

100%

96%

78%

93%

60%

100%

(18/18)

(27/28)

(7/9)

(14/15)

(3/5)

(8/8)

Genotype 6

80%

100%

75%

100%

(8/10)

(1/1)

N/A

N/A

(3/4)

(2/2)

“At Merck, we continue to build upon our clinical experience using grazoprevir/elbasvir across diverse populations of patients infected with chronic hepatitis C virus,” said Dr. Eliav Barr, vice president, infectious diseases, Merck Research Laboratories. “We remain on track to submit a New Drug Application with the U.S. Food and Drug Administration in the first half of 2015.”

C-EDGE TN Overview and Additional Findings
C-EDGE TN is a randomized, blinded, placebo-controlled trial evaluating the efficacy and safety of grazoprevir/elbasvir in treatment-naïve patients with or without cirrhosis infected with chronic HCV GT1, 4 or 6 who received therapy for 12 weeks. Patients were randomized to an immediate treatment group that received grazoprevir/elbasvir for 12 weeks or to a deferred treatment group that received placebo for 12 weeks, were followed for an additional four weeks, and then received open label grazoprevir/elbasvir for the next 12 weeks. The primary efficacy analysis included those patients who received immediate treatment with grazoprevir/elbasvir or placebo. Of the 316 patients who received immediate treatment with grazoprevir/elbasvir, 50 percent were infected with GT1a, 42 percent with GT1b, six percent with GT4 and three percent with GT6. Overall, 22 percent of patients had liver cirrhosis.

In this study, virologic failure occurred in 13 patients (4%) in the immediate treatment group, including one virologic breakthrough and 12 virologic relapses. Serious adverse events occurred in nine (3%) and three (3%) patients in the immediate treatment and corresponding placebo arms, respectively; none were considered drug-related. The most common adverse events reported (greater than 5% incidence) in the immediate treatment and corresponding placebo groups, were headache (17%, 18%), fatigue (16%, 17%), nausea (9%, 8%) and arthralgia (6%, 6%), respectively.

C-EDGE CO-INFXN Overview and Additional Findings
C-EDGE CO-INFXN is an open label, single-arm study evaluating the efficacy and safety of grazoprevir/elbasvir in treatment-naïve patients with or without cirrhosis infected with chronic HCV GT1, 4 or 6 and HIV who received therapy for 12 weeks. Of the 218 patients enrolled in the trial, 66 percent were infected with HCV GT1a, 21 percent with GT1b or other GT1, 13 percent with GT4, and one percent with GT6. Overall, 16 percent of patients had liver cirrhosis.
In this study, virologic failure occurred in seven patients (3%), including six virologic relapses and one reinfection. There were no reported drug-related serious adverse events. The most common (greater than 5% incidence) adverse events reported were fatigue (13%), headache (12%) and nausea (9%).

C-EDGE TE Overview and Additional Findings
C-EDGE TE is a randomized study evaluating the efficacy and safety of once-daily grazoprevir/elbasvir with or without twice-daily RBV in treatment-experienced (prior null response, partial response or relapse with peg-interferon/RBV) patients with or without cirrhosis infected with chronic HCV GT1, 4 or 6 who received therapy for 12 weeks or 16 weeks.

12 week arms
 Of the 209 patients randomized to the 12 week arms, 105 patients received grazoprevir/elbasvir only and 104 patients received grazoprevir/elbasvir plus RBV. Patients in the grazoprevir/elbasvir only arm comprised 58 percent GT1a, 33 percent GT1b or other GT1 and nine percent GT4. Overall, 35 percent had liver cirrhosis. Among the 104 patients receiving grazoprevir/elbasvir plus RBV, 58 percent were infected with chronic HCV GT1a, 28 percent GT1b or other GT1, and 14 percent GT4. Overall, 34 percent had liver cirrhosis.

In the grazoprevir/elbasvir only and grazoprevir/elbasvir plus RBV arms, six patients in each arm (6%) were reported to have virologic relapse. No patients were reported to have virologic breakthrough or rebound. Serious adverse events were reported in four patients in the grazoprevir/elbasvir only arm (4%) and three patients in the grazoprevir/elbasvir plus RBV arm (3%). The most common (greater than 10% incidence) adverse events reported in the grazoprevir/elbasvir and grazoprevir/elbasvir plus RBV arms, respectively, were fatigue (19%, 27%), headache (21%, 20%) and nausea (9%, 14%).

16 week arms
Of the 211 patients enrolled in the 16 week arms, 105 patients received grazoprevir/elbasvir only and 106 patients received grazoprevir/elbasvir plus RBV. In the grazoprevir/elbasvir only arm, 46 percent were infected with chronic HCV GT1a, 46 percent with GT1b or other GT1, five percent with GT4 and four percent with GT6. Overall, 36 percent of patients had liver cirrhosis. Among those in the grazoprevir/elbasvir plus RBV arm, 55 percent were infected with chronic HCV GT1a, 36 percent with GT1b or other GT1, eight percent with GT4, and two percent with GT6. Overall, 35 percent had liver cirrhosis.

Among the patients receiving grazoprevir/elbasvir only, three patients (3%) were reported to have virologic breakthrough or rebound and four patients (4%) were reported to have virologic relapse. No virologic failures occurred in patients receiving grazoprevir/elbasvir plus RBV. Serious adverse events were reported in three patients in the grazoprevir/elbasvir only arm (3%) and four patients in the grazoprevir/elbasvir plus RBV arm (4%). The most common (greater than 10% incidence) adverse events reported in the grazoprevir/elbasvir and grazoprevir/elbasvir plus RBV arms, respectively, were fatigue (16%, 30%), headache (19%, 19%) and nausea (4%,17%).

About the C-EDGE Program
C-EDGE is the Phase 3 clinical development program for Merck’s investigational HCV treatment grazoprevir/elbasvir comprising five studies with more than 1,700 patients across more than 25 countries. These studies are evaluating grazoprevir/elbasvir in multiple genotypes (GT1, 4 and 6) and diverse patient populations, including difficult-to-treat patients such as: treatment-experienced, patients with cirrhosis, HIV/HCV co-infection, advanced chronic kidney disease, inherited blood disorders, and those receiving opiate substitution therapies.

Read complete press release here...

EASL 2015: CNIO Researchers Link Telomeres to the Origins of Liver Diseases such as Chronic Hepatitis and Cirrhosis

• Researchers have generated a mouse with dysfunctional telomeres in the liver and, as a result, it developed cellular alterations present in human diseases such as hepatitis or cirrhosis
• This study is the first to show that alterations in the functioning of telomeres lead to changes in the liver that are common to diseases such as hepatitis and cirrhosis, which are associated with an increased risk of liver cancer
• This finding provides the basis for understanding the molecular origin of these diseases, as well as identifying new therapeutic strategies for their prevention and control

Madrid (Spain), April 16, 2015. Telomeres are DNA regions at the ends of our chromosomes that protect the genetic data of cells, preventing mutations and alterations in the DNA that could potentially cause disease. Telomeres shorten throughout life in a process involving both genetic and environmental factors. Telomere dysfunction —alterations in the structure and/or functioning of telomeres— is one of the molecular mechanisms underlying a number of age-related diseases but, to date, little is known about its possible role in pathologies of the liver such as cirrhosis, hepatitis and liver cancer.

In a study published in the Journal of Hepatology, Fabian Beier and Paula Martínez —from the Spanish National Cancer Research Centre´s (CNIO) Telomere and Telomerase Group led by Maria Blasco— have created a mouse model that recapitulates the origin of human diseases associated with long-term or chronic liver damage, such as hepatitis or cirrhosis of the liver which, in turn, can progress to liver cancer over time. This new mouse model reveals telomeric dysfunction as a potential factor in triggering these diseases.

Read more...

Janssen Announces SVR12 Rates with Twelve Weeks of Treatment with All-Oral, Once-Daily Regimen of Simeprevir Plus Sofosbuvir in Genotype 1 HCV Patients With and Without Cirrhosis

– Data from OPTIMIST-1 and OPTIMIST-2 Trials Showing SVR12 Rates of 97 Percent and 84 Percent to be Presented at The International Liver Congress™ 2015 of the European Association for the Study of the Liver -

– SVR12 Rates of up to 100 Percent Achieved Among Subgroups in Both Trials –

CORK, Ireland--(BUSINESS WIRE)--Janssen Sciences Ireland UC, one of the Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen), today announced results for its hepatitis C treatment simeprevir at The International Liver Congress™ 2015 of the European Association for the Study of the Liver (EASL) in Vienna. Late-breaking results from the Phase 3 OPTIMIST-1 and OPTIMIST-2 trials highlight the clinical outcomes of simeprevir in an all-oral combination regimen in a wide range of patients with hepatitis C virus (HCV) infection.

“Chronic HCV infection is a leading cause of cirrhosis, and once it is developed, these patients can be very difficult to cure. The results of the OPTIMIST-2 study demonstrate the safety and efficacy of the all-oral regimen of simeprevir and sofosbuvir for genotype 1 chronic HCV patients with cirrhosis”

“The new data for simeprevir presented at The International Liver Congress™ confirms its efficacy when combined with sofosbuvir in an all-oral, ribavirin-free regimen for HCV patients, including those who are treatment-naïve and treatment-experienced, both with and without cirrhosis,” said Gaston Picchio, hepatitis disease area leader, Janssen. “These data further demonstrate the role of simeprevir within the HCV treatment landscape, as it provides patients with an important therapeutic option.”

The results from the OPTIMIST-1 and OPTIMIST-2 trials are the first Phase 3 data to be presented on simeprevir in combination with sofosbuvir (SMV/SOF) in patients with genotype 1 chronic HCV infection, both with and without cirrhosis. Sofosbuvir is a nucleotide analog NS5B polymerase inhibitor developed by Gilead Sciences, Inc.

OPTIMIST-1¹

• OPTIMIST-1 is a Phase 3, randomised, open-label trial to investigate the efficacy and safety of the all-oral regimen of SMV/SOF among treatment-naïve and treatment-experienced genotype 1 chronic HCV-infected patients without cirrhosis. The primary objective was to show superior sustained virologic response (SVR) at 12 weeks after treatment (SVR12) with 12 and eight weeks of treatment with SMV/SOF versus a historical control (patients previously treated with approved regimens containing a direct-acting antiviral, pegylated interferon and ribavirin).
• Ninety-seven (97) percent of patients treated with SMV/SOF for 12 weeks (n=150/155) achieved SVR12, which was superior to the SVR12 rate of 87 percent among the historical control.
  • SVR12 rates of 100 percent were seen among patients with IL28B CC genotype (n=43/43) and those with baseline NS5A and NS3 Q80K polymorphisms (n=9/9).
• Patients treated with eight weeks of SMV/SOF achieved an SVR12 rate of 83 percent (n=128/155), which was not superior to the SVR12 rate of 83 percent in the historical control.
  • High SVR12 rates were seen among patients with baseline HCV RNA <4 million IU/mL (96 percent; n=46/48), IL28B CC genotype (93 percent; n=38/41), patients with genotype 1b HCV infection (92 percent; n=36/39) and patients without baseline NS5A and Q80K polymorphisms (89 percent; n=78/88).
• The most frequently reported adverse events in the 12-week and eight-week treatment arms were headache (14 and 17 percent, respectively), fatigue (12 and 15 percent, respectively) and nausea (15 and 9 percent, respectively).

OPTIMIST-2²

• OPTIMIST-2 is a Phase 3, open-label, single-arm trial to investigate the efficacy and safety of SMV/SOF in treatment-naïve and treatment-experienced genotype 1 chronic HCV-infected patients with cirrhosis. The primary objective was to show superior SVR12 with 12 weeks of treatment with SMV/SOF versus a historical control.
• Twelve (12) weeks of treatment with SMV/SOF resulted in SVR12 rates of 84 percent (n=86/103), which was superior to the SVR12 rate of 70 percent in the historical control.
• Higher SVR12 rates were seen in patients with baseline NS5A polymorphisms with or without NS3 Q80K polymorphisms (100 percent; n=13/13), patients with albumin ≥4 g/dL (94 percent; n=47/50) and treatment-naïve patients (88 percent; n=44/50).
• The most common adverse events were fatigue (20 percent), headache (20 percent) and nausea (11 percent).

“Chronic HCV infection is a leading cause of cirrhosis, and once it is developed, these patients can be very difficult to cure. The results of the OPTIMIST-2 study demonstrate the safety and efficacy of the all-oral regimen of simeprevir and sofosbuvir for genotype 1 chronic HCV patients with cirrhosis,” said Eric Lawitz, M.D., Texas Liver Institute, principal investigator of the OPTIMIST-2 study.

About Janssen’s HCV Development Programme
The goal of the Janssen hepatitis C virus (HCV) clinical development programme is to provide physicians with multiple treatment options in order to offer patients the best possible chance at successful therapy.

Ongoing studies focus on the investigation of the NS3/4A protease inhibitor simeprevir in a number of different treatment combinations and HCV patient populations, including those who are difficult to cure.

Janssen’s HCV pipeline also includes JNJ-56914845, an investigational NS5A replication complex inhibitor currently in Phase 2 studies, and following the acquisition of Alios BioPharma by Johnson & Johnson in November 2014, AL-335, a uridine-based nucleotide analog in Phase 1 development, and AL-516, a guanosine-based nucleotide analog NS5B polymerase inhibitor in pre-clinical development.

These compounds are being developed with the intent of targeting critical steps of the HCV replication cycle.

About Simeprevir (OLYSIO^®)
Simeprevir is an NS3/4A protease inhibitor which has been developed by Janssen Sciences Ireland UC in collaboration with Medivir AB.

In November 2013, simeprevir was initially approved by the U.S. Food and Drug Administration, and in May 2014, it was granted marketing authorisation by the European Commission. Subsequent marketing authorisations have followed in several other countries around the world. Indications vary by market.

Janssen is responsible for the global clinical development of simeprevir and has exclusive, worldwide marketing rights, except in the Nordic countries. Medivir AB retains marketing rights for simeprevir in these countries under the marketing authorisation held by Janssen-Cilag International NV.

Read complete press release here...

EASL 2015: Hepatitis C Infection Linked to Increased Risk of Heart Disease

Results from a new study demonstrate that chronic hepatitis C virus (HCV) infection is associated with a higher risk of developing cardiovascular diseases and significantly increases cost of care and length of time in hospital. Based on these results, revealed today at The International Liver Congress 2015, study investigators conclude that chronic HCV infection should be considered a risk factor for the development of cardiovascular diseases.

In the study, inpatient prevalence of diagnosed HCV infection was 1.9%. For these patients, the adjusted odds ratio (OR) for acute myocardial infarction was 2.29 (CI: 2.22?2.36); for coronary artery disease: 1.88 (CI: 1.83?1.93); for cerebrovascular accident: 1.98 (CI: 1.93?2.04) and for congestive heart failure: 1.08 (CI: 1.06-1.10).

In this study, patients with HCV infections were characterized using the weighted 2011 Nationwide Inpatient Sample (NIS) data.

Read more...

Merck Announces Results from Phase 2/3 Study of Investigational Chronic Hepatitis C Therapy Grazoprevir/Elbasvir in Patients with Advanced Chronic Kidney Disease

C-SURFER Trial is First to Investigate an All-Oral Ribavirin-Free Hepatitis C Treatment Regimen in Treatment-Naïve and Treatment-Experienced Patients with Advanced Chronic Kidney Disease Infected with Hepatitis C Virus Genotype 1 

VIENNA--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the first presentation of data from C-SURFER, the company’s Phase 2/3 clinical trial evaluating the investigational once-daily treatment regimen of grazoprevir (100mg) and elbasvir (50mg) in patients with advanced chronic kidney disease (CKD) infected with chronic hepatitis C virus (HCV) genotype 1 (GT1).¹ Treatment-naïve patients and patients who failed prior pegylated interferon HCV therapy, with or without cirrhosis, all of whom had CKD stages 4 or 5, were enrolled.² Following 12 weeks of treatment with grazoprevir and elbasvir, 99 percent (115/116) of patients in the pre-specified primary population for analysis of efficacy data achieved a sustained virologic response 12 weeks after the completion of treatment (SVR12).³ These data will be presented today at The International Liver Congress^TM 2015 – the 50^th annual congress of the European Association for the Study of the Liver (late breaking E-Poster #LP02).

“There is an unmet medical need to treat chronic hepatitis C virus infection in patients with advanced chronic kidney disease,” said Dr. Howard Monsour, Jr., chief of hepatology, Houston Methodist Hospital, Houston, Texas. “In this trial, the first to investigate an all-oral ribavirin-free treatment regimen in treatment-naïve and treatment-experienced CKD patients, treatment with grazoprevir and elbasvir for 12 weeks was effective in this study population with HCV genotype 1 infection.”

The ongoing C-SURFER Phase 2/3 clinical trial is a randomized, parallel-group, placebo-controlled study evaluating patients infected with chronic HCV GT1 with advanced CKD with or without liver cirrhosis. Patients were randomized to one of two study arms:

• Immediate treatment group (ITG), grazoprevir plus elbasvir (blinded) once-daily for 12 weeks (n=111);
• Deferred treatment group (DTG), initially placebo (control arm) for 12 weeks followed by a four week follow-up period and then treatment with grazoprevir plus elbasvir (open label) once-daily for 12 weeks (n=113).

In addition, 11 patients received grazoprevir plus elbasvir (open label) once-daily for 12 weeks with intensive pharmacokinetic sampling.

Of the 122 patients who received grazoprevir plus elbasvir, 83 percent were treatment-naïve, 36 percent had diabetes, 18 percent had stage 4 CKD, 82 percent had stage 5 CKD, 75 percent were receiving hemodialysis and 45 percent were African-American. Among those patients who received at least one dose of grazoprevir plus elbasvir, five percent (6/122) were excluded from the pre-specified primary efficacy analysis population, or modified full analysis set, due to missing data caused by death or early discontinuation for reasons unrelated to study drug. In the modified full analysis set, 99 percent (115/116) of patients receiving grazoprevir plus elbasvir achieved SVR12. One GT1b infected, non-cirrhotic, interferon-intolerant patient showed a viral relapse at follow-up week 12. Within the modified full analysis set, efficacy was consistent across the patient sub-populations assessed. In a supportive analysis of all 122 patients who received at least one dose of grazoprevir plus elbasvir in the ITG arms, including patients who did not complete the study for reasons not related to study drug, 94 percent (115/122) of patients achieved SVR12.

“Merck’s broad clinical development program includes studies dedicated to bringing a once-daily regimen to diverse populations of patients infected with chronic HCV, including certain types of patients with co-morbidities, such as advanced chronic kidney disease,” said Dr. Eliav Barr, vice president, infectious diseases, Merck Research Laboratories. “These data highlight how emerging innovations in chronic hepatitis C treatment may lead to new options for patient populations in which it historically has been difficult to achieve high rates of sustained viral clearance.”

No patients in the ITG arms discontinued treatment due to adverse events (AEs), while four percent (5/113) of patients in the comparator placebo phase of the DTG arm discontinued treatment due to AEs. The rates of serious AEs reported were 14 percent (16/111) in the ITG arms and 17 percent (19/113) in the placebo control DTG arm. The most common treatment-related AEs in the ITG arms and DTG arm (placebo) were headache (17%, 17%), nausea (15%, 16%) and fatigue (10%, 15%), respectively. There were four deaths reported during the initial treatment phase and the first 14 days of study follow-up. One patient (1%) in the open label arm died from cardiac arrest (not considered related to study medicine) and three patients (2%) in the placebo group died from aortic aneurysm, pneumonia and an unknown cause.

On April 8, 2015, the company announced that the U.S. Food and Drug Administration (FDA) had granted Breakthrough Therapy designation to grazoprevir/elbasvir for the treatment of patients infected with chronic HCV GT1 with end-stage renal disease on hemodialysis and patients infected with chronic HCV GT4. 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.

About C-SURFER
C-SURFER is a Phase 2/3 clinical trial evaluating Merck’s investigational grazoprevir plus elbasvir in patients infected with chronic HCV GT1 and with advanced chronic kidney disease (stages 4 and 5, including patients on hemodialysis) with or without liver cirrhosis, which are among those with HCV infection who are most difficult to treat, over 12 weeks.

About Chronic HCV Infection and Chronic Kidney Disease
Chronic HCV infection is both a cause and complication of the treatment of CKD. In patients with CKD, chronic HCV infection is associated with an increased risk of accelerated loss of remaining kidney function, kidney transplant failure and death. Furthermore, patients with chronic HCV infection and advanced CKD represent an unmet need due to a lack of demonstrated HCV treatment options for this group.

About Grazoprevir/Elbasvir
Grazoprevir/elbasvir is an investigational, once-daily single tablet regimen consisting of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A replication complex inhibitor). As part of Merck’s broad clinical trials program, grazoprevir/elbasvir is being studied in multiple HCV genotypes and in patients with difficult-to-treat conditions such as HIV/HCV co-infection, advanced chronic kidney disease, inherited blood disorders, liver cirrhosis and those on opiate substitution therapy.

Read complete press release here...

Janssen Highlights Hepatitis C Virus Development Programme at The International Liver Congress™ 2015 of the European Association for the Study of the Liver (EASL)

Presentations include late-breaking final results from the Phase 3 OPTIMIST trials and interim results from the Phase 2 IMPACT trial of simeprevir

CORK, Ireland--(BUSINESS WIRE)--Janssen Sciences Ireland UC, one of the Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen), today announced that clinical data for simeprevir, its NS3/4A protease inhibitor for the treatment of hepatitis C virus (HCV) infection, will be presented at The International Liver Congress™ 2015 of the European Association for the Study of the Liver (EASL) taking place in Vienna from April 22-26. Early-stage data on the investigational nucleotide analog polymerase inhibitors AL-335 and AL-516, which were recently obtained through Janssen’s acquisition of Alios BioPharma, will also be presented.

“Janssen has an extensive and ongoing clinical trial programme for hepatitis C, including confirmatory and new exploratory studies, and we look forward to sharing these results. We remain focused on investigating alternative and more immediate treatment options for patients with a high unmet need.”

Several key presentations will report on the efficacy and tolerability of simeprevir in interferon-free combination regimens in Phase 2, Phase 3 and real-world clinical settings.

“Hepatitis C remains a serious health problem. The breadth of data we are presenting at The International Liver Congress™ reinforces our commitment to reducing the significant burden of this infectious disease around the world,” said Gaston Picchio, hepatitis disease area leader, Janssen. “Janssen has an extensive and ongoing clinical trial programme for hepatitis C, including confirmatory and new exploratory studies, and we look forward to sharing these results. We remain focused on investigating alternative and more immediate treatment options for patients with a high unmet need.”

A total of 14 company-sponsored abstracts supporting Janssen’s marketed and investigational therapies for HCV will be presented, including three abstracts on simeprevir accepted as late-breaking presentations. The scope and rigor of these data underscore Janssen’s commitment to being a positive catalyst in the fight against this serious public health threat.

“These data highlight the strength of our commitment to advancing research in the area of viral hepatitis,” said Lawrence M. Blatt, Ph.D., global head therapeutics, Janssen Infectious Diseases and Vaccines, and president and chief executive officer of Alios BioPharma. “We are delighted to present additional data for simeprevir in combination with other currently available therapeutic options alongside early-stage data for our nucleotide portfolio.”

Studies on Janssen’s HCV portfolio to be presented at The International Liver Congress™ 2015 include:

 
Late-Breaking Poster Presentations
All posters will be displayed electronically from Thursday 23 April, 07:30 to Saturday 25 April, 20:00 in Hall B.

• A Phase 3, randomised, open-label study to evaluate the efficacy and safety of 12 and 8 weeks of simeprevir (SMV) plus sofosbuvir (SOF)▼ in treatment-naïve and -experienced patients with chronic HCV genotype 1 infection without cirrhosis: The OPTIMIST-1 study¹
  • Abstract LP14
  • Lead Author: P. Kwo; Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University, Indianapolis, IN, USA

• A Phase 3, open-label, single-arm study to evaluate the efficacy and safety of 12 weeks of simeprevir (SMV) plus sofosbuvir (SOF) in treatment-naïve or -experienced patients with chronic HCV genotype 1 infection and cirrhosis: The OPTIMIST-2 study²
  • Abstract LP04
  • Lead Author: E. Lawitz; Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX, USA

• Simeprevir (SMV) plus daclatasvir (DCV)▼ and sofosbuvir (SOF) in treatment-naïve and -experienced patients with chronic hepatitis C virus genotype 1 or 4 infection and decompensated liver disease: Interim results from the Phase 2 IMPACT study¹
  • Abstract LP07
  • Lead Author: E. Lawitz; Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX, USA

Oral Presentation

• On-treatment virologic response and tolerability of simeprevir, daclatasvir and ribavirin in patients with recurrent hepatitis C virus genotype 1b infection after orthotopic liver transplantation (OLT): Interim data from the Phase 2 SATURN Study¹
  • Abstract 0004: Thursday 23 April, 16:45 – 17:00, Hall D
  • Lead Author: X. Forns; Liver Unit, Hospital Clinic, Barcelona, Spain

Poster Presentations
All posters will be displayed electronically from Thursday 23 April, 07:30 to Saturday 25 April, 20:00 in Hall B.

• Significant drug-drug interaction between simeprevir and cyclosporine A but not tacrolimus in patients with recurrent chronic HCV infection after orthotopic liver transplantation: The SATURN study¹
  • Abstract P0834
  • Lead Author: S. Ouwerkerk-Mahadevan; Janssen Research & Development, Beerse, Belgium
• Deep sequencing analyses in HCV genotype 1-infected patients treated with simeprevir plus sofosbuvir with/without ribavirin in the COSMOS study⁶
  • Abstract P0780
  • Lead Author: B. Fevery; Janssen Infectious Diseases BVBA, Beerse, Belgium
• Effectiveness of simeprevir (SMV)-containing regimens among patients with chronic hepatitis C virus (HCV) in various U.S. practice settings: Interim analysis of the SONET study⁷
  • Abstract P0826
  • Lead Author: I. Alam; Austin Hepatitis Center, Austin, TX, USA
• Study protocol for a partly randomised, open-label Phase 2a trial of once-daily simeprevir combined with sofosbuvir for the treatment of HCV genotype 4-infected patients with or without cirrhosis (OSIRIS)⁸
  • Abstract P1346
  • Lead Author: M. El Raziky, Departments of Pediatrics, Cairo University, Cairo, Egypt
• Baseline factors associated with increased SVR rates in 123 treatment-naïve chronic HCV genotype 1 patients treated with a shortened 12-week simeprevir plus pegylated interferon and ribavirin regimen: A multivariate analysis⁹
  • Abstract P0792
  • Lead Author: T. Asselah, Beaujon Hospital, University of Paris, France
• Clinical characteristics and outcomes of chronic hepatitis C (CHC) patients treated with newer direct-acting antiviral (DAA)-based regimens from a large U.S. payer perspective¹⁰
  • Abstract P0852
  • Lead Author: N. Tandon; Janssen Scientific Affairs, LLC, Titusville, NJ, USA
• A descriptive analysis of a real-world population with chronic hepatitis C (CHC) treated with simeprevir (SMV)-and/or sofosbuvir (SOF)-based regimens: Findings from a U.S. payer database¹¹
  • Abstract P0827
  • Lead Author: J.B. Forlenza; Janssen Scientific Affairs, LLC, Titusville, NJ, USA
• Real world effectiveness and cost of simeprevir- and/or sofosbuvir-based HCV treatments: $175,000 per SVR12¹²
  • Abstract P0881
  • Lead Author: K. Bichoupan; Division of Liver Diseases, Icahn School of Medicine at the Mount Sinai Medical Center, New York, NY, USA

Alios BioPharma Poster Presentations

• Derisking the potential for mitochondrial toxicity of nucleoside analogs¹³
  • Abstract P0679
  • Lead author: Z. Jin; Alios BioPharma, San Francisco, CA, USA
• Preclinical characterization of AL-335, a potent uridine based nucleoside polymerase inhibitor for the treatment of chronic hepatitis C¹⁴
  • Abstract P0682
  • Lead Author: H. Tan; Alios BioPharma, San Francisco, CA, USA

Full session details and data presentation listings for The International Liver Congress™ 2015 can be found at http://www.ilc-congress.eu.

Press Release Source: 

AbbVie to Present New Data from Hepatitis C Clinical Development Program at The International Liver Congress™ 2015

- 29 abstracts,  including sub-analyses of AbbVie's approved treatment of VIEKIRAX® + EXVIERA®, as well as new data from Phase 3b development program and AbbVie's HCV pipeline compounds  

NORTH CHICAGO, Ill., April 8, 2015 /PRNewswire/ -- AbbVie today announced that 29 abstracts from its ongoing hepatitis C clinical development program have been accepted for presentation during The International Liver CongressTM (ILC) 2015 in Vienna, Austria from April 22-26. Data being presented include sub-analyses of the recently approved VIEKIRAX® (ombitasvir/paritaprevir/ritonavir tablets) + EXVIERA® (dasabuvir tablets), Phase 3b studies, including a head-to-head comparison of AbbVie's three direct-acting antiviral treatment with telaprevir-based therapy and Phase 2/3 studies investigating AbbVie's combination treatment in genotype 1 (GT1) and genotype 4 (GT4). Additionally, data from Phase 1 studies of ABT-493 and ABT-530 will be presented.

"We are pleased to present new investigational data at ILC that reinforces our broad HCV clinical development program beyond the approval of VIEKIRAX + EXVIERA," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "We are studying the diverse populations seen in clinical practice and expanding our research and development, including our new HCV pipeline compounds."

AbbVie's ongoing HCV pipeline development program focuses on investigating a pan-genotypic, ribavirin (RBV)-free, once-daily treatment that may also allow for treatment durations of as little as eight weeks. Preliminary results from a Phase 2b study (n=79) of ABT-493 and ABT-530 in non-cirrhotic GT1 patients receiving the RBV-free recommended regimen for 12 weeks demonstrated a sustained virologic response rate at four weeks post treatment (SVR4) of 99 percent (n=78/79). These results, announced for the first time today, included both GT1a and GT1b, treatment-naïve and pegylated-interferon and RBV prior null responders. Patients across both study arms were randomized to receive ABT-493 (200mg) and either 120mg or 40mg of ABT-530. To date, the most common (>5 percent) adverse reactions were fatigue, headache, nausea, diarrhea and anxiety. Data from these Phase 2b studies of ABT-493 and ABT-530 will not be presented at ILC 2015, and will be released at future medical congresses.

Abstracts for AbbVie's HCV Pipeline Compounds:

• Pharmacokinetics of ABT-493 and ABT-530 is Similar in Healthy Caucasian, Chinese and Japanese Adult Subjects; Wang, T; ePoster # P0855
• Steady-state Pharmacokinetics and Safety of Co-administration of Pan-genotypic, Direct Acting Protease Inhibitor, ABT-493 with Pan-genotypic NS5A Inhibitor, ABT-530, in Healthy Adult Subjects; Lin, C; ePoster # P0715

Abstracts for Approved VIEKIRAX and EXVIERA:

• Long-Term Follow-up of Treatment-emergent Resistance-associated Variants in NS3, NS5A and NS5B with Paritaprevir/r-, Ombitasvir- and Dasabuvir-based Regimens; Krishnan, P; Oral Presentation, Viral Hepatitis C: Clinical Session, Friday, April 24 at 4:15pm–4:30pm CEST; # O057
• Implications of Baseline HCV RNA Level and Intrapatient Viral Load Variability on OBV/PTV/R + DSV 12-Weeks Treatment Outcomes; Brown, R; ePoster # LP39
• High SVR Rates Despite Multiple Negative Predictors in Genotype 1 Patients Receiving Ombitasvir/Paritaprevir/R, Dasabuvir with or without Ribavirin for 12 and 24 Weeks: Integrated Analysis of Six Phase 3 Trials; Bernstein, D; ePoster # P0781
• Pharmacokinetics of Paritaprevir, Ombitasvir, Ritonavir and Ribavirin in Subjects with HCV Genotype 4 Infection; Eckert, D; ePoster # P0823
• Improvement in Liver Function and Non-Invasive Estimates of Liver Fibrosis 48 Weeks After Treatment with Ombitasvir/Paritaprevir/R, Dasabuvir and Ribavirin in HCV Genotype 1 Patients with Cirrhosis; Wedemeyer, H; ePoster # P0808
• Pharmacokinetics of Paritaprevir, Ombitasvir, Dasabuvir, Ritonavir and Ribavirin in Subjects with HCV Genotype 1 Infection in Phase 3 Studies; Mensing, S; Khatri, A; ePoster # P0820
• Exposure-Response Analyses for Efficacy (SVR12) for the Direct Acting Antiviral Regimen of ABT-450/R, Ombitasvir with Dasabuvir ± Ribavirin in Subjects with HCV Genotype 1 Infection; Khatri, A; ePoster # P0902
• Adherence to Ombitasvir/Paritaprevir/R, Dasabuvir, and Ribavirin is >98% in the SAPPHIRE-I and SAPPHIRE-II Trials; Hassanein, T; ePoster # P0908

Abstracts for Phase 3b Program:

• Safety of Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir for Treating HCV GT1 Infection in Patients with Severe Renal Impairment or End-stage Renal Disease: The RUBY-I Study; Pockros, P; Oral Presentation, Late Breakers Session, Saturday, April 25 at 4:00pm–4:15pm CEST
• MALACHITE-I: Phase 3b Trial of Ombitasvir/Paritaprevir/R and Dasabuvir+/-Ribavirin or Telaprevir + Peginterferon/Ribavirin in Treatment-Naïve Adults with HCV Genotype 1; Conway, B; ePoster # P0842
• MALACHITE-II: Phase 3b Trial of Ombitasvir/Paritaprevir/R and Dasabuvir + Ribavirin or Telaprevir + Peginterferon/Ribavirin in Peginterferon/Ribavirin Treatment-Experienced Adults with HCV Genotype 1; Dore, G; ePoster # P0847
• Phase 3b Studies to Assess Long-term Clinical Outcomes in HCV GT1-Infected Patients Treated with Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir with or without Ribavirin; Dumas, E; ePoster # P1331

Abstracts for AbbVie's HCV Investigational Treatment:

• Ombitasvir/Paritaprevir/Ritonavir for Treatment of HCV Genotype 1b in Japanese Patients with or without Cirrhosis: Results from GIFT-I; Sato, K; Rodrigues-Jr, L; Oral Presentation, General Session 3 & Award Ceremony 2: Saturday, April 25 at 8:30am–8:45am CEST; # G13
• A Randomized, Open-label Study to Evaluate Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir Co-administered with Ribavirin in Adults with Genotype 4 Chronic Hepatitis C Infection and Cirrhosis; Asselah, T; ePoster # P1345
• An Open-label Study to Evaluate the Efficacy and Safety of Co-formulated Ombitasvir/Paritaprevir/Ritonavir with Ribavirin in Adults with Chronic HCV Genotype 4 Infection in Egypt; Doss, W; ePoster # P1351
• No Significant Interaction Among Ombitasvir/Paritaprevir/Ritonavir ± Dasabuvir and Sofosbuvir; King, J; ePoster # P0905

Abstracts for Health Economics and Outcomes Research (HEOR) and Other AbbVie Data:

• The Public Health Value of Sparing Livers for Transplantation Through Systematic Treatment of Hepatitis C; Stevens, W; Juday, T; ePoster # P0025
• Healthcare Costs by Stage of Liver Disease in Chronic Hepatitis C Patients in the United States; Walker, D; ePoster # P0719
• The Value of Survival Benefits from Treating Hepatitis C at Different Fibrosis Stages with All-oral, Interferon-free Therapy Relative to 'Watchful Waiting'; Gonzalez, Y; ePoster # P0806
• Cost-effectiveness of Treating Different Stages of Genotype 1 Hepatitis C Virus (HCV) with AbbVie 3D (ABT-450/Ritonavir/Ombitasvir and Dasabuvir) +/- Ribavirin Compared to No Treatment in the United States; Samp, J; ePoster # P0815
• Reduction in Annual Medical Costs with Early Treatment of HCV Using AbbVie 3D (ABT-450/Ritonavir/Ombitasvir and Dasabuvir) +/- Ribavirin in the United States; Samp, J; ePoster # P0816
• Percent of Subjects Experiencing Liver Morbidity Over A Lifetime Horizon with AbbVie 3D (ABT-450/Ritonavir/Ombitasvir And Dasabuvir) Versus No Treatment; Samp, J; ePoster # P0850
• Public Health Impact of HCV Screening and Treatment in the French Baby-boomer Population; Ethgen, O; ePoster # P1245
• Impact of Pill Count on Medication Adherence During the First 12 Weeks of HIV Antiviral Treatment: Implications for HCV Treatment; Walker, D; ePoster # P0741
• The Impact of Ribavirin on Real World Adherence and Discontinuation Rates in HCV Patients Treated with Sofosbuvir + Simeprevir; Walker, D; Juday, T; ePoster # P0864    
• Ombitasvir/Paritaprevir /Ritonavir and Dasabuvir with Ribavirin (RBV) has Minimal Impact on Health-Related Quality of Life (HRQoL) Compared with Placebo During 12-Week Treatment in Treatment-Naïve Adults with Chronic Hepatitis C (CHC); Liu, Y; ePoster # P0873
• Ombitasvir/Paritaprevir /Ritonavir and Dasabuvir with Ribavirin (RBV) has Mild Impact on Health-Related Quality of Life (HRQoL) Compared with Placebo During 12-Week Treatment in Treatment-Experienced Adults with Chronic Hepatitis C (CHC); Liu, Y; ePoster # P0856

The full ILC 2015 scientific program can be found at www.ilc-congress.eu/.

Read complete press release here: