Summary from AASLD 2014 for Hepatitis C - Main points of discussion with current HCV therapy

Summary from AASLD 2014 for Hepatitis C
Boston 7-11 November 2014

Feedback from the real-world: do HCV cure rates in real-life patient cohorts hold what clinical trials promised?

Jurgen K. Rockstroh M.D., Professor of Medicine
University of Bonn, Germany

Correspondence:
Prof. Dr. J.K. Rockstroh
Department of Medicine I
University of Bonn
Sigmund-Freud-Str. 25
53105 Bonn
Germany
Tel.: +49-228-287 16558
FAX: +49-228-287 15034
e-mail: juergen.rockstroh@ukb.uni-bonn.de

Introduction

After this year EASL it appeared as if numerous interferon- and ribavirin-free DAA combinations were emerging which all promised HCV cure rates above 95% and that other than cost and treatment access issues the revolution of HCV therapy was taking place at an incredible pace leaving little room for further optimization. One of the frequently raised caveats however, was the lack of data in the so-called more difficult to treat "real-life patients" with higher rates of previous non-response to IFN-based therapies and cirrhosis. Also data on more challenging patient groups with additional comorbidities such as renal impairment or from the transplant setting were still scarce. Which role would ribavirin play in the future? How short could HCV treatment duration possibly become?

Clearly there were still many questions floating around from clinical practice. Therefore, this year AASLD was met with high expectations and interest as first data from the increasing use of DAA based HCV therapy from clinical practice outside of clinical trials was to be presented. A great summary on all HCV data was presented at AASLD (reviewing a proud number of 423 HCV presentations including 44 orals and 379 posters on HCV related topics) from Professor Fried and can be assessed through the AASLD website (1). The following conference report aims at covering the main HCV trials and clinical relevant HCV management issues presented at AASLD in Boston from 6-11 November 2014. It does not aim at completeness as the number of presentations on HCV therapy was higher than ever and covering all would produce an unreadable report but rather aims at capturing the main points of discussion with current HCV therapy.

Continue reading @ NATAP

AASLD - Investigational HCV Combo Delivers in Differing Groups

Investigational HCV Combo Delivers in Differing Groups

Published: Nov 16, 2014

By Ed Susman, Contributing Writer, MedPage Today
Reviewed by F. Perry Wilson, MD, MSCE; 

Assistant Professor, Section of Nephrology, Yale School of Medicine

Action Points

• Note that a trial of a three-drug direct-acting drug regimen against HCV revealed that a short course was associated with some degree of sustained virologic response, but did not perform as well as longer courses.
• Another trial of combination direct acting therapy found that SVR rates were very high even without the addition of ribavirin.

BOSTON -- A new study suggests that some subgroups of patients with hepatitis C (HCV) infection can achieve sustained virologic responses (SVR) in as short as 4 weeks using an aggressive, investigational three-drug regimen, researchers reported here.

In the 4-week duration part of a multi-arm clinical trial, all 31 non-cirrhotic genotype 1 HCV-infected patients achieved undetectable virus at follow-up week 2. according to Eric Lawitz, MD, of the Texas Liver Institute in San Antonio.

But by week 8, 19 of those patients had relapsed, giving an SVR rate of 38.7%, Lawitz reported in his poster presentation and at a press briefing at the annual meeting of the American Association for the Study of Liver Diseases.

Among the 30 patients treated for 6 weeks, all reached undetectable virus by follow-up week two, but four of those patients later relapsed, giving an 86.7% SVR at week 8.
"This is a phase II study. This is a proof of principle that we can accomplish SVR at 8 weeks," Lawitz told MedPage Today. "This was the first time there was a planned 4-week duration trial. Even though there were a number of relapses, it is biologically plausible to cure a very select subset of patients at 4 weeks."

The researchers conducting the so-called C-SWIFT trial also looked at 6-week and 8-week courses of treatment for harder-to-cure cirrhotic genotype 1 HCV patients.

"Cirrhotics had SVR of about 95% at 8 weeks," Lawitz said. He noted that all 102 patients in the study -- cirrhotics and non-cirrhotics -- achieved undetectable virus by follow-up week two. Among the cirrhotic patients, four patients out of 20 who were treated for 6 weeks relapsed. There was one relapse among the 21 cirrhotic patients treated for 8 weeks.

"There are some valuable lessons learned from this," Lawitz said. "It is encouraging to see a three-drug regimen achieve a 95% SVR at 8 weeks in the setting of cirrhosis. It shows we may be able to get to an 8-week regimen for all patient types.

"Our study looks at short duration therapy," Lawitz said. The registration trial for the two investigative agents will show SVR12 results. "In the C-SWIFT trial, which is ongoing, we used a three-drug regimen of grazoprevir and elbasvir -- the investigative drugs -- and sofosbuvir, which is already on the market."

"What we saw at the end of 4 weeks was that all but six patients had achieved undetectable virus, but by follow-up week two those six patients went on to be undetectable, so at follow-up week two there was 100% of patients that were undetectable." he said.

"In the 6-week arm, all but one patient was negative at the end of the treatment and that patient also went on to become negative by follow-up week two. In the cirrhotic arms all patients were undetectable at either 6 or 8 weeks," he said.

Lawitz said the three-drug regimen was well-tolerated with few serious adverse events occurring in any treatment regimen, possibly a factor of the short treatment duration.

In commenting on the research, press conference moderator Michael Fried, MD, director of the University of North Carolina Liver Center, Chapel Hill, told MedPage Today, "I agree that this is a very important study because it does sort of set the limits of where we might be able to go with these drugs in terms of duration of therapy.

"Everyone is sort of focused on shorter duration of therapy, and perhaps we can identify certain subgroups that may be able to get treated for 4 weeks, but it certainly will require a lot more research in that area."

The patients in the C-SWIFT study were in their 50s and more than 60% of each arm of the trial were men. More than 75% of the patients were diagnosed with genotype 1a. Lawitz said the overall study also includes patients diagnosed with genotype 3 hepatitis C virus infection, but the results from that group will be reported at a later meeting.

Meanwhile, the same drugs, but without sofosbuvir, appeared to allow difficult to treat HCV patients to attain a sustained virologic response with or without the addition of ribavirin, Lawitz reported in a separate presentation.

The C-WORTHY was a randomized, dose response, parallel-group, multiple-site, double-blind clinical trial comparing diverse patient populations exposed to different durations of treatment of grazoprevir/elbasvir with or without ribavirin in patients with chronic hepatitis C virus infection.
In C-WORTHY Parts A and B which were presented at AASLD, 471 patients with chronic hepatitis C virus genotype 1 infection were enrolled and randomized. The research was published online in The Lancet simultaneously with presentation at the meeting.
At the meeting, Lawitz reported:

• 28 of 31 cirrhotic patients naïve to antiviral therapy – 90% -- treated for 12 weeks with the fixed dose combination of grazoprevir 100 mg plus elbasvir 50 mg once daily plus ribavirin achieved the goal of sustained virologic response at 12 weeks (SVR₁₂). There were two late relapses in this group.
• 28 of 29 similar patients –97% -- treated for 12 weeks with the dual investigative drug without ribavirin achieved SVR₁₂. There was one relapse.
• 31 of 32 similar patients – 97% -- treated for 18 weeks with all 3 drugs achieved SVR₁₂. There were no relapses in this group.
• 29 of 31 similar patients – 94% -- treated for 18 weeks without ribavirin achieved SVR₁₂. There were two relapses.
• 30 of 32 null responders with or without cirrhosis – 94% -- treated for 12 weeks with the three drugs achieved SVR₁₂. There were no relapses.
• 30 of 33 similar patients –91% -- treated for 12 weeks with the two investigational drugs achieved SVR₁₂. There were three relapses in this group.
• 33 or 33 null responders with or without cirrhosis –100% -- treated for 18 weeks with all three drugs achieved SVR₁₂. There were no relapses.
• 31 of 32 similar patients – 97% -- treated with the two investigational drugs for 18 weeks achieved SVR₁₂. There were no relapses.

"High efficacy was observed regardless of the presence or absence of ribavirin or extended treatment duration from 12 weeks to 18 weeks," Lawitz said in his oral presentation during a special hepatitis plenary session at the annual meeting of the American Association for the Study of Liver Diseases..

Session moderator Anna Lok, MD, of the University of Michigan in Ann Arbor, told MedPage Today, "The data are impressive."

The combination is "is going through Phase III clinical trials so we will have to see what those results look like. If the Phase II results are confirmed, the treatment will be approved," Lok said.

"I don't think we can say that one regimen will be superior to another, but it is comparable to other treatments we have seen. That means that we have more choices. If we have more choices then maybe the prices will come down a bit through competition. That's what we all hope."

Grazoprevir/elbasvir (formerly known as MK-5172/MK-8742 consists of grazoprevir, an oral, once-daily NS3/4A protease inhibitor, and elbasvir, an oral, once-daily NS5A inhibitor.

The treatment naïve patients in the study arms were about 58 years old; the treatment experienced null responders were about 54 years of age. There were more men than women in the study and more than 90% of the patients in the study arms were white. Almost all the patients in the treatment naïve population had cirrhosis (one patient did not). About 35% of patients who were null responders had cirrhosis.

Adverse events were infrequent. Lawitz said the treatment was well-tolerated. He noted that more adverse events were noted when ribavirin was added to the treatment regimen.

Merck plans to submit the New Drug Application to the FDA for grazoprevir/elbasvir in 2015.

Source - MedPage Today

Weekend Reading - AASLD 2014: Overview with expert commentary on key studies presented at the meeting

AASLD 2014: Overview with expert commentary on key studies presented at the meeting

*Updated Nov 16 to include HCV Advocate's Mid-Month Publication 

Good day folks, welcome to another edition of Weekend Reading.

Is everyone thinking about celebrating Thanksgiving? If only I had time to ready my new abode for the upcoming holiday, but Nana has been diverted by a clever 30 pound Zombie hunting mutant ninja turtle!

Every morning while I attempt to plan the families menu,  I hear a gentle tap, tap at my door, waiting on the other side is my three year old grandson ready for the hunt. Off we go racing through Nana's complex in search of Zombies. To date we saved three ladybugs, two spiders and one plastic cat without a tail. Although we did find a ladder leading up to the roof, wow, imagine our excitement as we climbed to the top only to realize the hatch was firmly locked, my complex is secure!

Anyhow, if you too are searching for Zombies on this fine Saturday, please do carry on. However, if you came by for a bit of weekend reading, we begin with HCV Advocates Mid-Month Newsletter:

HCV Advocate's Mid-Month Edition



In This Issue:
Genotype 3
Alan Franciscus, Editor-in-Chief
In the past, HCV genotype 3 was thought to be one of the easiest to cure. As a result there was little incentive to develop newer therapies especially since there were fewer people with genotype 3 in developed countries. Now we know that of all HCV genotypes 1 through 4, genotype 3 is the hardest to treat and cure with HCV inhibitor therapy.

Read more...


Hepatitis C in Canada
—Cheryl Reitz, MA & CD Mazoff, PhD
Canada has a large population with hepatitis C, but there is no national strategy in place for testing or treatment. While the new HCV inhibitors are slowly being approved, access to them and whether they will be covered under "Pharmacare" plans differs widely from province to province. 

Read more...


Alan Franciscus, Editor-in-Chief
Read about whether there is a relationship between HCV and diabetes, the use of Sovaldi for post-transplant infection, shorter treatment times and the continuum of HCV testing and care. 

Read more...


Preparing Your Medical Record for Disability
Jacques Chambers, CLU
Transitioning from work to disability is a major life event with all the confusion, frustration, and emotional upheaval such events can bring. Now is the time to start getting your medical record into a shape that will support disability, if and when it is needed. 

Read more...




What's New
Alan Franciscus, Editor-in-Chief
Hepatitis C Vaccine Shows Promise
FDA Approves Olysio/Sovaldi Combo
Read more...

New & Updated Spanish Easy C Facts
Alan Franciscus, Editor-in-Chief
Ayuda con Medicamentos (Help with Medicines)
Tratamiento para Genotipo 1: Harvoni (Sofosbuvir & Ledipasvir).
Read more...

Over at ViralEd check out a review of this months liver meeting. The Live eSymposium took place on November 11, the replay is available here, or click here to view the EU edition featuring Europe-based clinicians reporting on the meeting.

Don't forget to watch for an On-Demand Program reviewing the meeting - coming soon at  ViralEd.

Independent reporting from AASLD 

Hepatitis C: Management and Treatment

Commentary by 

Mark Sulkowski, MD

Nezam H. Afdhal, MD

K. Rajender Reddy, MD

Fred Poordad, MD

Program Overview
While an increasing number of options are available or in development for effectively treating patients with HCV infection, many clinicians find it challenging to keep abreast of important developments in HCV therapeutics. This 1.5-hour Internet symposium will feature independent reporting on, review and discussion of the key studies on chronic hepatitis C presented at the 65th American Association for the Study of Liver Diseases Annual Meeting (AASLD 2014).

The expected result is that participants will not only gain an increased understanding of key data presented at AASLD 2014, they will also be better prepared to address their HCV patients' health needs and provide optimal care, which should improve adherence, increase individualized care, reduce adverse effects and drug-drug interactions, and improve quality of life.

Begin Here.......

For additional coverage check out Clinical Care Options CCO for an in-depth program overview with capsule summaries and expert commentary covering key studies presented at the meeting, updated November 14.

CORAL-1: High SVR Rates With 24 Weeks of All-Oral Paritaprevir/Ritonavir/Ombitasvir + Dasabuvir and Ribavirin in Patients With Recurrent Genotype 1 HCV After Liver Transplantation
97% of patients in this historically challenging patient population achieved SVR12, with no episodes of acute or chronic liver graft rejection.
Date Posted: 11/14/2014

High SVR12 Rates in Pooled Analysis of Phase III Trials of Paritaprevir/RTV/Ombitasvir + Dasabuvir ± Ribavirin in Cirrhotic and Noncirrhotic Patients With Genotype 1a HCV Infection
The addition of ribavirin resulted in higher SVR rates, and extension of therapy to 24 weeks beneficial for cirrhotic patients with a previous null response to peginterferon/ribavirin.

TURQUOISE-II Subanalysis: Most Baseline Characteristics Not Associated With SVR12 to Paritaprevir/RTV/Ombitasvir Plus Dasabuvir and Ribavirin in Patients With Genotype 1 HCV Infection and Cirrhosis
In logistic regression analysis, IL28B TT genotype, previous null response to peginterferon/ribavirin, and genotype 1a HCV only factors significantly associated with not achieving SVR12.

Retreatment With Ledipasvir/Sofosbuvir + RBV Highly Efficacious, Safe in Patients With Genotype 1 HCV Infection Who Failed Previous Sofosbuvir-Based Therapy
Among the 50 patients with genotype 1 HCV infection in this study, 100% achieved SVR12 after 12 weeks of retreatment; single relapse was misclassified patient later found to have genotype 3a HCV infection.

UNITY-1: High SVR12 Rates Following 12 Weeks of Daclatasvir/Asunaprevir/Beclabuvir in Treatment-Naive and Previously Treated Noncirrhotic Patients With Genotype 1 HCV
SVR12 rate of approximately 90% for both treatment-naive and treatment-experienced patients.

Ledipasvir/Sofosbuvir + Ribavirin Safe and Effective for Treatment of HCV in Patients With Decompensated Cirrhosis
High SVR12 rates and improved liver function with low rates of treatment-emergent adverse events.

C-SWIFT: Initial Results Show All-Oral Regimen of Grazoprevir/Elbasvir + Sofosbuvir for 6-8 Weeks Effective and Safe in Treatment-Naive Noncirrhotic and Cirrhotic Patients With Genotype 1 HCV Infection
SVR4/8 rates higher in patients with genotype 1b HCV infection, IL28B CC genotype, or lower baseline HCV RNA level.

8-Week Regimen of Sofosbuvir + GS-5816 With or Without Ribavirin Effective but Resulted in SVR Rates Lower Than Previously Seen With 12 Weeks in Treatment-Naive Noncirrhotic Patients With Genotype 1 or 2 HCV Infection
In this phase II trial, sofosbuvir plus GS-5816 with or without ribavirin was generally safe and well tolerated with only 1 patient discontinuing treatment because of adverse events.

Final C-WORTHY Results: Grazoprevir + Elbasvir ± RBV Yields High SVR12 Rates in Genotype 1 Treatment-Naive Cirrhotic Patients and Previous Null Responders
SVR12 rates ≥ 90% were attained regardless of RBV use or treatment duration.

ALLY-3: High SVR12 Rates With 12 Weeks of Daclatasvir + Sofosbuvir in Treatment-Naive or Treatment-Experienced Patients With Genotype 3 HCV Infection
SVR12 rates substantially lower for both treatment-naive and treatment-experienced cirrhotics vs noncirrhotics.

ELECTRON-2: High SVR12 Rates With Sofosbuvir + NS5A Inhibitor GS-5816 With or Without Ribavirin in Treatment-Naive, Noncirrhotic Genotype 3 HCV–Infected Patients in Phase II Trial
Low levels of discontinuation due to adverse events; no virologic failure with 100-mg dose of GS-5816. Inclusion of ribavirin associated with more frequent adverse events with no efficacy benefit.

HCV-TARGET: Real-World Use of Sofosbuvir-Containing Regimens Yields Overall SVR4 Rates ≥ 85% in Patients With Genotype 1 or 2 HCV Infection
To date, regimens allowing removal of peginterferon most commonly selected: sofosbuvir plus ribavirin in patients with genotype 2/3 infection and sofosbuvir plus simeprevir with or without ribavirin in genotype 1 HCV infection.

Ledipasvir/Sofosbuvir Regimens Highly Effective, Safe, and Well Tolerated in Patients With Genotype 1 HCV and Compensated Cirrhosis
Similar SVR12 rates with 24-week ribavirin-free regimen vs 12-week ribavirin-containing regimen in treatment-experienced cirrhotics.

HCV Management (Coming soon)

HCV Management (Coming soon)

HCV Management (Coming soon)

Traditionally Hard-to-Treat HCV (Coming soon)

Traditionally Hard-to-Treat HCV (Coming soon)

Traditionally Hard-to-Treat HCV (Coming soon)

All-Oral Fixed-Dose Combination Therapy With Daclatasvir/Asunaprevir/BMS-791325 ± Ribavirin for Patients With Chronic HCV Genotype 1 Infection and Compensated Cirrhosis: UNITY-2 Phase III SVR12 Results (Coming soon)

Source: Official Conference Coverage
2014 Annual Meeting of the American Association for the Study of Liver Diseases

Coverage on hepatitis B is available at Hepatitis B Foundation, reported by Christine Kukka.

AASLD 2014 Liver Meeting – HBV Coverage

AASLD Links

Comprehensive data investigating HCV interferon-free, ribavirin-free regimens presented at the liver meeting is now available on this blogs 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

NATAP
Healio
HIV and Hepatitis

Medscape
MedPage Today

Of Interest

Media-Investment Commentary 

FierceBiotech 

Seeking Alpha 

The Post AASLD Annual Meeting Hepatitis C Landscape

See you all soon, enjoy the weekend.

Tina

It’s Here: CCO’s Official Conference Coverage of AASLD 2014‏

Official Conference Coverage of the 2014 Annual Meeting of the American Association for the Study of Liver Diseases

Capsule Summaries
Reviews by expert faculty on key studies highlighted at the conference
Downloadable slides
Review Conference Coverage

Ledipasvir/Sofosbuvir Regimens Highly Effective, Safe, and Well Tolerated in Patients With Genotype 1 HCV and Compensated Cirrhosis
Similar SVR12 rates with 24-week ribavirin-free regimen vs 12-week ribavirin-containing regimen in treatment-experienced cirrhotics.
Review the Full Capsule

HCV-TARGET: Real-World Use of Sofosbuvir-Containing Regimens Yields Overall SVR4 Rates ≥ 85% in Patients With Genotype 1 or 2 HCV Infection
To date, regimens allowing removal of peginterferon most commonly selected: sofosbuvir plus ribavirin in patients with genotype 2/3 infection and sofosbuvir plus simeprevir with or without ribavirin in genotype 1 HCV infection.
Review the Full Capsule

ELECTRON-2: High SVR12 Rates With Sofosbuvir + NS5A Inhibitor GS-5816 With or Without Ribavirin in Treatment-Naive, Noncirrhotic Genotype 3 HCV-Infected Patients in Phase II Trial
Low levels of discontinuation due to adverse events; no virologic failure with 100-mg dose of GS-5816. Inclusion of ribavirin associated with more frequent adverse events with no efficacy benefit.
Review the Full Capsule

ALLY-3: High SVR12 Rates With 12 Weeks of Daclatasvir + Sofosbuvir in Treatment-Naive or Treatment-Experienced Patients With Genotype 3 HCV Infection
SVR12 rates substantially lower for both treatment-naive and treatment-experienced cirrhotics vs noncirrhotics.
Review the Full Capsule

Final C-WORTHY Results: Grazoprevir + Elbasvir ± RBV Yields High SVR12 Rates in Genotype 1 Treatment-Naive Cirrhotic Patients and Previous Null Responders
SVR12 rates ≥ 90% were attained regardless of RBV use or treatment duration.
Review the Full Capsule

VIDEO: Hepatitis C screening rises, but where are the positive cases?

VIDEO: Hepatitis C screening rises, but where are the positive cases?

By: PATRICE WENDLING, Family Practice News Digital Network 

NOVEMBER 14, 2014

BOSTON– The number of hepatitis C virus antibody tests increased by 15.4% after the 2012 Centers for Disease Control and Prevention task force recommendation calling for one-time HCV testing in baby boomers, according to preliminary results from an analysis of 4.5 million tests.

Surprisingly, that increase in testing did not lead to an increase in the number of positive tests, which actually declined by 4.1%, R. Monina Klevens, D.D.S., MPH, reported at the annual meeting of the American Association for the Study of Liver Diseases.

“This is a huge question that we need to look at for implementation,” said Dr. Klevens, a medical epidemiologist with the CDC.

Video

For a deep dive into the data and to hear what’s next, click here to see an interview with Dr Klevens.

Dr. Klevens reported no financial disclosures.

The Post AASLD Annual Meeting Hepatitis C Landscape

Investment Commentary @ Seeking Alpha

The Post AASLD Annual Meeting Hepatitis C Landscape
Leonard Yaffe

Summary

• Advances in efficacy, treatment duration and side effect elimination continue.
• Interferon use will largely disappear, and Ribavirin will be reserved primarily for difficult to treat sub-populations.
• Gilead continues to advance the state of the art, and Merck has a competitive regimen.

Following the AASLD 2014 (American Association for the Study of Liver Disease) Annual Meeting, these are my thoughts regarding Hepatitis C pharmacotherapy:

The goal of pharmacotherapy is a high cure rate and a reduced cost. The extremely high success rates (95% SVR 12) lower costs by decreasing retreatments and complications. Costs are also lessened by shorter treatment time, lower per-unit pricing and the elimination of IFN (interferon) and RBV (ribavirin) from the regimen. In this regard, I expect an increasing move toward 8 week therapy, especially in treatment naïve patients. Furthermore, I believe that IFN use will be virtually eliminated, and RBV use will be dramatically reduced, reserved primarily for hard to treat sub-populations (IFN cost is much more relevant). I cannot comment on per-unit pricing and rebates except that I think AbbVie (NYSE:ABBV) will be involved in the latter due to my perception that its regimen is inferior, the extent to which will be determined by the need for RBV.

Continue reading....

Merck To Submit NDA For Grazoprevir/Elbasvir in 2015

Final Results from the C-WORTHy Study (Parts A and B) Presented at The Liver Meeting^® and Published in The Lancet

First Wave of Phase 3 Development Program for Grazoprevir/Elbasvir is Fully Enrolled; Merck Plans to Submit New Drug Application in 2015

BOSTON--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the presentation of results from a multi-arm Phase 2 clinical trial evaluating grazoprevir/elbasvir (MK-5172/MK-8742), the company’s investigational NS3/4A protease inhibitor and NS5A inhibitor, respectively) with or without ribavirin (RBV) in treatment-naïve and previously-treated (with peg-interferon/ribavirin [PR]) patients with chronic hepatitis C virus (HCV) genotype 1 (GT1) infection -- the C-WORTHy study (Parts A and B). The final results were presented in oral sessions at the 65^th American Association for the Study of Liver Diseases (AASLD) Annual Meeting (also known as The Liver Meeting^®) and published as separate papers online in The Lancet.

“We are encouraged by the findings for grazoprevir/elbasvir in the C-WORTHy trial and look forward to advancing our broad Phase 3 program, which includes hard-to-cure patients that are of the highest need and least studied to date.”

“Merck is committed to developing an efficacious, well-tolerated therapy suitable for a broad spectrum of patients with HCV,” said Dr. Eliav Barr, vice president, infectious diseases, Merck Research Laboratories. “We are encouraged by the findings for grazoprevir/elbasvir in the C-WORTHy trial and look forward to advancing our broad Phase 3 program, which includes hard-to-cure patients that are of the highest need and least studied to date.”

Interim results from the C-WORTHy study were presented in April 2014 at the 49^th Annual Meeting of the European Association for the Study of the Liver (EASL) and announced by Merck.

Results for Treatment-Naïve Cirrhotic Patients and PR Null-Responders
The results for HCV mono-infected treatment-naïve GT1 patients with cirrhosis and GT1 prior null-responders with or without cirrhosis treated with grazoprevir/elbasvir, with or without ribavirin, for 12 weeks or 18 weeks are shown in table 1. The rates of sustained viral response,ⁱ 12 weeks after the completion of therapy (SVR12) were greater than, or equal to, 90 percent regardless of treatment duration or co-administration of RBV.



The rate of virologic failure was five percent (6/123) in treatment-naïve cirrhotic patients and three percent (4/130) in the null-responder population. Treatment was generally well-tolerated. The most common adverse events associated with the administration of grazoprevir/elbasvir in combination with or without RBV were: fatigue (26%), headache (23%) and asthenia (14%). There were no early discontinuations due to adverse events with grazoprevir/elbasvir and no clinically significant abnormalities observed in routinely evaluated biomarkers.

Results for HCV Mono-Infected and HIV/HCV Co-Infected Patients
Treatment-naïve, non-cirrhotic mono-infected GT1 patients and non-cirrhotic HCV GT1 /HIV co-infected patients treated for 12 weeks with grazoprevir/elbasvir with or without RBV, demonstrated high rates of SVR12, as seen in table 2. Among this patient population treated for 12 weeks, the overall rate of virologic failure was four percent (7/188), including three breakthrough failures and four relapses, in both mono- and co-infected patients. In patients treated for eight weeks, the rate of virologic failure was 17 percent (5/30), with five relapses. The most common adverse events with or without RBV were fatigue (23%), headache (20%), nausea (15%) and diarrhea (10%). There were no early discontinuations due to adverse events with grazoprevir/elbasvir and no clinically significant abnormalities observed in routinely evaluated biomarkers.

Table 2
Grazoprevir/ Elbasvir Treatment Duration (wks)		HCV Mono-infected						HIV/HCV Co-infected
		8***		12		12		12		12
RBV		+RBV		+RBV		-RBV		+RBV		-RBV
SVR12 (n/m) [95% confidence interval]		80% (24/30*) [61, 92]		93% (79/85*) [85, 97]		98% (43/44) [88, 100]		97% (28/29) [82, 100]		87% (26/30*) [69, 96]
iiVirologic Failure		5		3**†		1		1		2
* 4 HCV mono-infected patients (1 in the 8-wk and 3 in the 12-wk +RBV arms) and 2 HIV/HCV co-infected patients in the -RBV arm were lost to follow-up.
**Virologic breakthrough was seen in 1 patient, which was a new infection with HCV GT2b (or a minor GT2b variant at baseline).
***GT1a patients only.
†1 of the patients who relapsed did not receive grazoprevir and received only elbasvir plus RBV for the first month of treatment.

About the C-WORTHy Study
C-WORTHy is a randomized, dose response, parallel-group, multiple-site, double-blind clinical trial comparing diverse patient populations exposed to different durations of treatment of grazoprevir/elbasvir with or without RBV in patients with chronic HCV infection. In C-WORTHy Parts A and B, a total of 471 patients with chronic HCV GT1 infection with HCV RNA levels of =10,000 IU/mL were enrolled and randomized across 16 arms. The patients include hard-to-cure sub-populations, including treatment-naïve patients with liver cirrhosis (12- and 18-week arms, with and without RBV) and prior-null responder patients with and without cirrhosis (12- and 18-week arms, with and without RBV). The lead authors of The Lancet publications and presenters at The Liver Meeting^® are Dr. Eric Lawitz of The Texas Liver Institute and professor of medicine at The University of Texas Health Science Center, San Antonio, TX (C-WORTHy Cirrhotic Patients and Prior Null-Responders); and Dr. Mark Sulkowski, professor of medicine at The Johns Hopkins University School of Medicine, Baltimore, MD (C-WORTHy HCV Mono-Infected and HIV/HCV Co-Infected Patients).

About C-EDGE: Merck’s Phase 3 HCV Program
The results of the C-WORTHy study supported the advancement of grazoprevir/elbasvir into the Phase 3 clinical development program called C-EDGE. The Phase 3 C-EDGE program is evaluating grazoprevir/elbasvir with and without RBV in various genotypes and across a broad range of patient populations with chronic HCV infection, including treatment-naive patients and patients who previously failed PR therapy, patients with and without cirrhosis, patients with chronic kidney disease (including those on hemodialysis), patients with HIV/HCV co-infection, patients on opiate substitution therapy and patients with inherited blood disorders. Merck initiated the first C-EDGE study in April 2014, and the grazoprevir/elbasvir registration studies within the C-EDGE program – including C-EDGE TN (treatment-naïve), C-EDGE CO-INFXN (HIV/HCV co-infected) and C-EDGE TE (treatment-experienced) -- are now fully enrolled. Results from these trials are anticipated in the first half of 2015. Learn more at http://www.merck.com/clinical-trials/.

About Grazoprevir/Elbasvir
Grazoprevir/elbasvir (MK-5172/MK-8742) is an investigational, oral, once-daily, fixed-dose combination chronic HCV treatment, consisting of grazoprevir, an investigational oral, once-daily HCV NS3/4A protease inhibitor, and elbasvir, an investigational oral, once-daily HCV NS5A replication complex inhibitor. In October 2013, Merck announced that the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation to grazoprevir/elbasvir for treatment of chronic HCV infection. Breakthrough Therapy designation is intended to expedite the development and review of a candidate that is planned for use, alone or in combination, to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. Merck plans to submit the New Drug Application for grazoprevir/elbasvir in 2015.

AASLD-Merck C-WORTHy Results/Grazoprevir/Elbasvir in Geno 1 Treatment-Naïve and Difficult-to-Cure Patients

Merck Announces Results from Phase 2 Study of Investigational Chronic Hepatitis C Treatment Grazoprevir/Elbasvir in Genotype 1 Infected Treatment-Naïve and Difficult-to-Cure Patients

BOSTON, Nov 11, 2014 (BUSINESS WIRE) -- Merck MRK, +0.91% known as MSD outside the United States and Canada, today announced the presentation of results from a multi-arm Phase 2 clinical trial evaluating grazoprevir/elbasvir (MK-5172/MK-8742, the company’s investigational NS3/4A protease inhibitor and NS5A inhibitor, respectively) with or without ribavirin (RBV) in treatment-naïve and previously-treated (with peg-interferon/ribavirin [PR]) patients with chronic hepatitis C virus (HCV) genotype 1 (GT1) infection -- the C-WORTHy study (Parts A and B). The final results were presented in oral sessions at the 65th American Association for the Study of Liver Diseases (AASLD) Annual Meeting (also known as The Liver Meeting®) and published as separate papers online in The Lancet.

“Merck is committed to developing an efficacious, well-tolerated therapy suitable for a broad spectrum of patients with HCV,” said Dr. Eliav Barr, vice president, infectious diseases, Merck Research Laboratories. “We are encouraged by the findings for grazoprevir/elbasvir in the C-WORTHy trial and look forward to advancing our broad Phase 3 program, which includes hard-to-cure patients that are of the highest need and least studied to date.”

Interim results from the C-WORTHy study were presented in April 2014 at the 49th Annual Meeting of the European Association for the Study of the Liver (EASL) and announced by Merck.

Results for Treatment-Naïve Cirrhotic Patients and PR Null-Responders
The results for HCV mono-infected treatment-naïve GT1 patients with cirrhosis and GT1 prior null-responders with or without cirrhosis treated with grazoprevir/elbasvir, with or without ribavirin, for 12 weeks or 18 weeks are shown in table 1. The rates of sustained viral response,i 12 weeks after the completion of therapy (SVR12) were greater than, or equal to, 90 percent regardless of treatment duration or co-administration of RBV.

The rate of virologic failure was five percent (6/123) in treatment-naïve cirrhotic patients and three percent (4/130) in the null-responder population. Treatment was generally well-tolerated. The most common adverse events associated with the administration of grazoprevir/elbasvir in combination with or without RBV were: fatigue (26%), headache (23%) and asthenia (14%). There were no early discontinuations due to adverse events with grazoprevir/elbasvir and no clinically significant abnormalities observed in routinely evaluated biomarkers.

Results for HCV Mono-Infected and HIV/HCV Co-Infected Patients
Treatment-naïve, non-cirrhotic mono-infected GT1 patients and non-cirrhotic HCV GT1 /HIV co-infected patients treated for 12 weeks with grazoprevir/elbasvir with or without RBV, demonstrated high rates of SVR12, as seen in table 2. Among this patient population treated for 12 weeks, the overall rate of virologic failure was four percent (7/188), including three breakthrough failures and four relapses, in both mono- and co-infected patients. In patients treated for eight weeks, the rate of virologic failure was 17 percent (5/30), with five relapses. The most common adverse events with or without RBV were fatigue (23%), headache (20%), nausea (15%) and diarrhea (10%). There were no early discontinuations due to adverse events with grazoprevir/elbasvir and no clinically significant abnormalities observed in routinely evaluated biomarkers.

About the C-WORTHy Study
C-WORTHy is a randomized, dose response, parallel-group, multiple-site, double-blind clinical trial comparing diverse patient populations exposed to different durations of treatment of grazoprevir/elbasvir with or without RBV in patients with chronic HCV infection. In C-WORTHy Parts A and B, a total of 471 patients with chronic HCV GT1 infection with HCV RNA levels of greater-than or equal to 10,000 IU/mL were enrolled and randomized across 16 arms. The patients include hard-to-cure sub-populations, including treatment-naïve patients with liver cirrhosis (12- and 18-week arms, with and without RBV) and prior-null responder patients with and without cirrhosis (12- and 18-week arms, with and without RBV). The lead authors of The Lancet publications and presenters at The Liver Meeting® are Dr. Eric Lawitz of The Texas Liver Institute and professor of medicine at The University of Texas Health Science Center, San Antonio, TX (C-WORTHyCirrhotic Patients and Prior Null-Responders); and Dr. Mark Sulkowski, professor of medicine at The Johns Hopkins University School of Medicine, Baltimore, MD (C-WORTHy HCV Mono-Infected and HIV/HCV Co-Infected Patients).

About C-EDGE: Merck’s Phase 3 HCV Program
The results of the C-WORTHy study supported the advancement of grazoprevir/elbasvir into the Phase 3 clinical development program called C-EDGE. The Phase 3 C-EDGE program is evaluating grazoprevir/elbasvir with and without RBV in various genotypes and across a broad range of patient populations with chronic HCV infection, including treatment-naive patients and patients who previously failed PR therapy, patients with and without cirrhosis, patients with chronic kidney disease (including those on hemodialysis), patients with HIV/HCV co-infection, patients on opiate substitution therapy and patients with inherited blood disorders. Merck initiated the first C-EDGE study in April 2014, and the grazoprevir/elbasvir registration studies within the C-EDGE program – including C-EDGE TN (treatment-naïve), C-EDGE CO-INFXN (HIV/HCV co-infected) and C-EDGE TE (treatment-experienced) -- are now fully enrolled. Results from these trials are anticipated in the first half of 2015.
Learn more at http://www.merck.com/clinical-trials/.

About Grazoprevir/Elbasvir
Grazoprevir/elbasvir (MK-5172/MK-8742) is an investigational, oral, once-daily, fixed-dose combination chronic HCV treatment, consisting of grazoprevir, an investigational oral, once-daily HCV NS3/4A protease inhibitor, and elbasvir, an investigational oral, once-daily HCV NS5A replication complex inhibitor. In October 2013, Merck announced that the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation to grazoprevir/elbasvir for treatment of chronic HCV infection. Breakthrough Therapy designation is intended to expedite the development and review of a candidate that is planned for use, alone or in combination, to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. Merck plans to submit the New Drug Application for grazoprevir/elbasvir in 2015.

Also View:
AASLD Conference Reports: HCV Data, slide presentations categorized by genotype and pharmaceutical company

AASLD-Gilead Announces Harvoni Study Results in Chronic Hepatitis C Patients with Advanced Liver Disease and Those Who Failed Prior Treatment

Gilead Announces Harvoni Study Results in Chronic Hepatitis C Patients with Advanced Liver Disease and Those Who Failed Prior Treatment
-- High Cure Rates in Nearly 800 HCV Patients with Advanced Liver Disease --

BOSTON--(BUSINESS WIRE)--Nov. 11, 2014-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced results from several Phase 2 and Phase 3 studies evaluating investigational uses of Harvoni® (ledipasvir 90 mg/sofosbuvir 400 mg) for the treatment of chronic hepatitis C virus (HCV) infection in patients with limited or no treatment options, including patients with decompensated cirrhosis, patients with HCV recurrence following a liver transplant and patients who failed previous treatment with other direct acting antivirals. These data will be presented this week at the 65th Annual Meeting of the American Association for the Study of Liver Diseases (The Liver Meeting 2014) in Boston.

"Chronic hepatitis C patients with advanced liver disease are among the most difficult to cure and traditionally have had limited or no treatment options," said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer, Gilead Sciences. "The data presented this week demonstrate that Harvoni provides high cure rates for patients with advanced liver disease, as well as for those who failed prior treatment with other antivirals, including sofosbuvir-based regimens."

Harvoni was approved by the U.S. Food and Drug Administration and Health Canada in October 2014 and is the first once-daily single tablet regimen for the treatment of chronic HCV genotype 1 infection in adults. Applications are pending in the European Union, Japan and New Zealand.

Advanced Liver Disease

In a pooled analysis of Phase 2 and Phase 3 open-label studies (Oral #82) in more than 500 genotype 1 HCV infected patients with compensated cirrhosis who received Harvoni alone or with ribavirin (RBV) for 12 or 24 weeks, 96 percent of patients achieved sustained virologic response (SVR12). Patients who achieve SVR12 are considered cured of HCV infection.

Two prospective analyses from a Phase 2 open-label study (Study GS-US-337-0123) evaluating patients with decompensated cirrhosis and those with HCV recurrence following liver transplantation also are being presented. In the first subgroup (Oral #239), 108 genotype 1 and 4 infected patients with decompensated cirrhosis, including those with moderate hepatic impairment (Child-Pugh-Turcotte (CPT) Class B) and severe hepatic impairment (CPT Class C), received Harvoni plus RBV for 12 or 24 weeks. Overall, SVR12 rates were 87 percent (n=45/52) in the 12-week arm and 89 percent (n=42/47) in the 24-week arm.

The second subgroup (Oral #8) evaluated 12 or 24 weeks of Harvoni plus RBV among 223 genotype 1 and 4 patients who developed HCV recurrence following liver transplantation. Among non-cirrhotic patients, SVR12 rates were 96 percent (n=53/55) and 98 percent (n=55/56) following 12 and 24 weeks of treatment, respectively. For patients with compensated cirrhosis, SVR12 rates were 96 percent for both 12 weeks (n=25/26) and 24 weeks (n=24/25) of therapy. SVR12 rates among patients with decompensated cirrhosis were 81 percent for both 12 weeks (n=25/31) and 24 weeks (n=17/21) of therapy.

Retreatment of Patients Who Failed Prior Therapy

Study GS-US-337-0121 (Late Breaker Oral #LB-6) evaluated 155 genotype 1 patients with compensated cirrhosis who had failed prior treatment with pegylated interferon (PegIFN)/RBV and subsequently PegIFN/RBV plus a protease inhibitor. In this study, patients were randomized (1:1) to receive Harvoni plus RBV for 12 weeks or Harvoni alone for 24 weeks. Ninety-six percent (n=74/77) of those receiving Harvoni plus RBV for 12 weeks and 97 percent (n=75/77) of those receiving Harvoni for 24 weeks achieved SVR12.

In a second study (Oral #235), 51 genotype 1 patients who previously failed SOF/PegIFN/RBV, SOF/RBV or a SOF placebo/PegIFN/RBV treatment regimen received Harvoni plus RBV for 12 weeks. Twenty-nine percent of study patients (n=15/51) had cirrhosis. Ninety-eight percent (n=50/51) achieved SVR12 following 12 weeks of treatment with Harvoni plus RBV.

In all of these studies, Harvoni was well tolerated and its safety profile was generally consistent with that observed in clinical trials of Harvoni. Adverse events included fatigue, headache, nausea and anemia, which was more common among patients taking RBV. Grade 3/4 laboratory abnormalities were infrequent and included decreases in hemoglobin, which is consistent with RBV-associated anemia.

Also View:
AASLD Conference Reports: HCV Data, slide presentations categorized by genotype and pharmaceutical company

Gilead Announces Sofosbuvir Plus GS-5816 SVR12 Rates Across Multiple HCV Genotypes --

Gilead Announces Phase 2 Data for Investigational All-Oral Regimen of Sofosbuvir Plus GS-5816 for the Treatment of Chronic Hepatitis C

-- Once-Daily Combination Achieves High SVR12 Rates Across Multiple HCV Genotypes --

BOSTON--(BUSINESS WIRE)--Nov. 11, 2014-- Gilead Sciences, Inc. (Nasdaq:GILD) today announced data from three Phase 2 open-label studies evaluating the safety and efficacy of an investigational all-oral pan-genotypic regimen containing the nucleotide analog polymerase inhibitor sofosbuvir (SOF), approved as Sovaldi^® by the U.S. Food and Drug Administration in December 2013, and the investigational NS5A inhibitor GS-5816 for the treatment of chronic hepatitis C virus (HCV) infection. These data are being presented this week at the 65th Annual Meeting of the American Association for the Study of Liver Diseases (The Liver Meeting^® 2014) in Boston.

All three studies evaluated SOF 400 mg plus GS-5816 25 or 100 mg, with and without ribavirin (RBV), for eight or 12 weeks. Rates of sustained virologic response (SVR12) ranged from 88 percent to 100 percent among those receiving SOF plus GS-5816 100 mg for 12 weeks - the regimen selected for Phase 3 studies. Patients who achieve SVR12 are considered cured of HCV infection.

"There continues to be a need for simple, interferon- and ribavirin-free treatment regimens that are effective for all hepatitis C patients, regardless of genotype," said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer, Gilead Sciences. "These data demonstrate the high efficacy and tolerability of sofosbuvir plus GS-5816 among patients with varying genotypes and disease progression and we look forward to providing Phase 3 data on the combination across all six genotypes."

The first study, GS-US-342-0109 (Oral #197), evaluated 12 weeks of SOF plus GS-5816 with and without RBV in treatment-experienced genotype 1 and 3 patients with and without cirrhosis. The genotype 1 patients had all failed a prior treatment course that included a protease inhibitor. The number and proportion of patients achieving SVR12 are summarized in the table below.

The second study, ELECTRON 2 (Oral #79), evaluated the same combination of SOF plus GS-5816, with and without RBV, for eight weeks in non-cirrhotic, treatment-naïve genotype 3 patients. Patients receiving SOF with GS-5816 100 mg achieved SVR12 rates of 100 percent (n=26/26) with RBV and 96 percent (n=26/27) without RBV.

The third study, GS-US-342-0102, evaluated SOF plus GS-5816, with and without RBV, among non-cirrhotic treatment-naïve patients. The results of Part A of the study evaluating 12 weeks of therapy were presented at the 49th Annual Meeting of the European Association for the Study of the Liver (The International Liver Congress 2014) in April 2014.

The results of Part B, presented at the Liver Meeting this week (Oral #80), evaluated eight weeks of SOF plus GS-5816, with and without RBV, in patients with genotype 1 or 2 HCV infection. Among genotype 1 patients receiving SOF plus GS-5816 100 mg, SVR12 rates were 81 percent (n=25/31) and 90 percent (n=26/29), with and without RBV, respectively. Genotype 2 patients achieved SVR12 rates of 88 percent (n=23/26) with RBV and 88 percent (n=23/26) without RBV.

SOF plus GS-5816 was well tolerated in over 800 patients with HCV infection evaluated in these three studies. There was a low incidence of serious adverse effects and few discontinuations due to adverse events. The most frequently reported adverse events (>10%) were fatigue, headache, nausea and insomnia. The most frequently observed hematologic abnormality was hemoglobin decrease in the RBV-containing treatment groups.

GS-5816 is an investigational product and its safety and efficacy have not been established.

Additional information about these studies can be found at www.clinicaltrials.gov.

About Gilead Sciences

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North and South America, Europe and Asia Pacific.

Forward-Looking Statement

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 factors, including the possibility of unfavorable longer-term results from these studies and other ongoing and subsequent clinical trials involving sofosbuvir plus GS-5816, alone or in combination with other products, for the treatment of HCV. In addition, Gilead may make a strategic decision to discontinue development of GS-5816 if, for example, Gilead believes commercialization will be difficult relative to other opportunities in its pipeline. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead's Quarterly Report on Form 10-Q for the quarter ended September 30, 2014, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

U.S. Full Prescribing Information for Sovaldi is available at www.gilead.com.

Also View:
AASLD Conference Reports: HCV Data, slide presentations categorized by genotype and pharmaceutical company

AASLD Conference Reports: HCV Data, slide presentations categorized by genotype and pharmaceutical company

65th Annual Meeting of the American Association for the Study of Liver Diseases

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 

AASLD - AbbVie Results PEARL-I Study in Genotype 4 Chronic Hepatitis C Patients

AbbVie to Present Results from Phase 2 PEARL-I Study in Genotype 4 Chronic Hepatitis C Patients at The Liver Meeting® 2014

- Results demonstrated high response rates in adult chronic hepatitis C genotype 4 patients without cirrhosis

- Data underscore AbbVie's commitment to evaluating treatments across a range of patients with chronic hepatitis C virus infection

BOSTON, Nov. 11, 2014 /PRNewswire/ -- AbbVie (NYSE:ABBV) announced detailed results from its open-label Phase 2b study, PEARL-I, which demonstrated that 100 percent of genotype 4 (GT4) patients who were new to therapy (n=42/42) or who had failed previous treatment with pegylated interferon (pegIFN) and RBV (n=49/49) achieved sustained virologic response rates at 12 weeks post-treatment (SVR12) after taking AbbVie's investigational treatment with ribavirin (RBV). Additionally, 90.9 percent of patients who were new to therapy achieved SVR12 (n=40/44) after taking the treatment without RBV. These data will be presented today during a poster session at The Liver Meeting® 2014.

"As many as 34 million people around the world are living with genotype 4 chronic hepatitis C, a population that is common in the Middle East and Africa, where it accounts for more than 80 percent of all hepatitis C cases,[i]" said Barry Bernstein, M.D., vice president, infectious disease development, AbbVie. "The data from PEARL-I represent another important step forward in realizing our commitment to advancing scientific knowledge in hepatitis C with the ultimate goal of providing treatment options to as many patients as possible."

PEARL-I studied AbbVie's all-oral, interferon-free investigational treatment combining two direct-acting antivirals (ABT-450/ritonavir and ombitasvir) with and without RBV for 12 weeks in non-cirrhotic adult patients with chronic genotype 1b (GT1b) and GT4 hepatitis C virus (HCV) infection.

There were no discontinuations due to adverse events in PEARL-I. The most commonly reported treatment-emergent adverse events (greater than 15 percent in any group) were headache (29-33 percent), asthenia (weakness) (24-33 percent), fatigue (7-18 percent), nausea (9-17 percent) and insomnia (5-16 percent). One patient had a grade 3 liver function test elevation (AST> five times the upper limit of normal), which was asymptomatic and resolved during continued dosing. Four patients with hemoglobin decreases (anemia) required RBV dose reductions; however, none of these patients required blood transfusions or medication to boost their red blood cell production. In the treatment-naïve group without RBV, on-treatment virologic breakthrough was reported in one patient (2 percent) and two patients (5 percent) experienced post-treatment relapse. There were no virologic failures in the other treatment arms.

About AbbVie's Investigational Two Direct-Acting Antiviral HCV Treatment
AbbVie's proposed all-oral antiviral treatment consists of the fixed-dose combination of ABT-450/ritonavir (150/100mg) co-formulated with ombitasvir (25mg) dosed once daily, co-administered with weight-based ribavirin (1000mg or 1200mg in divided doses twice daily). The combination of two direct-acting antivirals, each with distinct mechanisms of action, targets and inhibits specific HCV proteins in the viral replication process.

About AbbVie's HCV Clinical Development Program
The AbbVie HCV clinical development program is intended to advance scientific knowledge and clinical care by investigating interferon-free, all-oral treatments with and without ribavirin with the goal of achieving high sustained virologic response rates in as many patients as possible. AbbVie's development programs combining two direct-acting antivirals are studying additional hepatitis C virus (HCV) genotypes.

ABT-450 was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors. ABT-450 is being developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of hepatitis C.

Safety Information for Ribavirin and Ritonavir
Ribavirin and ritonavir are not approved for the investigational use discussed above, and no conclusions can or should be drawn regarding the safety or efficacy of these products for this use.

There are special safety considerations when prescribing these drugs in approved populations.

Ritonavir must not be used with certain medications due to significant drug-drug interactions and in patients with known hypersensitivity to ritonavir or any of its excipients.

Ribavirin monotherapy is not effective for the treatment of chronic hepatitis C virus and must not be used alone for this use. Ribavirin causes significant teratogenic effects and must not be used in women who are pregnant or breast-feeding and in men whose female partners are pregnant. Ribavirin must not be used in patients with a history of severe pre-existing cardiac disease, severe hepatic dysfunction or decompensated cirrhosis of the liver, autoimmune hepatitis, hemoglobinopathies, or in combination with peginterferon alfa-2a in HIV/HCV co-infected patients with cirrhosis and Child-Pugh score =6.

AASLD - AbbVie Results Hepatitis C Patients with HIV-1 Co-Infection (TURQUOISE-I) and Liver Transplant Recipients (CORAL-I)

AbbVie to Present Results from Studies in Chronic Hepatitis C Patients with HIV-1 Co-Infection (TURQUOISE-I) and Liver Transplant Recipients (CORAL-I) at The Liver Meeting® 2014

- In adult patients co-infected with genotype 1 (GT1) hepatitis C virus (HCV) infection and human immunodeficiency virus (HIV) type 1 infection, TURQUOISE-I demonstrated sustained virologic response rates 12 weeks post-treatment (SVR(12)) of 93.5 percent after 12 weeks of treatment and 90.6 percent after 24 weeks of treatment, respectively

- In adult liver transplant patients with recurrent chronic GT1 HCV infection and new to treatment after transplantation, CORAL-I demonstrated 97.1 percent SVR rates at 12 and 24 weeks post-treatment after 24 weeks of treatment

- CORAL-I results published online today in The New England Journal of Medicine

BOSTON, Nov. 11, 2014 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced results from studies in chronic hepatitis C patients with human immunodeficiency virus type 1 (HIV-1) co-infection (TURQUOISE-I) and liver transplant recipients (CORAL-I) at The Liver Meeting®2014.

New, detailed results from part one of the Phase 2 portion of AbbVie's Phase 2/3 open-label study, TURQUOISE-I, showed patients co-infected with genotype 1 (GT1) hepatitis C virus (HCV) and HIV-1 receiving AbbVie's investigational treatment and ribavirin (RBV) for 12 weeks or 24 weeks achieved sustained virologic response rates 12 weeks post-treatment (SVR12) of 93.5 percent (n=29/31) and 90.6 percent (n=29/32), respectively. These data were presented today, November 11, as a "Poster of Distinction."

"Patients living with both chronic HCV and HIV have been historically considered more difficult to treat," said Barry Bernstein, M.D., vice president, infectious disease development, AbbVie. "TURQUOISE-I is one of the few dedicated studies looking specifically at this population, who are seen in everyday clinical practice. These data will help us gain a better understanding of how our investigational treatment works in this subpopulation of genotype 1 patients."

Additionally, results from the first cohort of AbbVie's ongoing open-label Phase 2 study, CORAL-I, were presented today during an oral session and published online in The New England Journal of Medicine. Results showed that non-cirrhotic liver transplant patients with recurrent GT1 HCV and new to treatment after transplantation achieved a SVR12 rate of 97.1 percent (n=33/34) and a sustained virologic response rate 24 weeks post-treatment (SVR24) of 97.1 percent (n=33/34) after 24 weeks of treatment.

"Recurrence of HCV infection in the new graft post-liver transplantation is universal in those that have the virus prior to transplantation, and can be associated with an aggressive disease course," explained Dr. Paul Kwo, medical director of liver transplantation and professor of medicine, Indiana University School of Medicine. "The high SVR rates seen in CORAL-I are promising and offer valuable information as we continue to assess this regimen within this specific patient population."

About TURQUOISE-I

TURQUOISE-I is an ongoing Phase 2/3, multi-center, randomized, open-label study evaluating the efficacy and safety of AbbVie's all-oral, interferon-free investigational treatment combining three direct-acting antivirals (ombitasvir/ABT-450/ritonavir and dasabuvir) with RBV (weight based dosing of 1000 mg or 1200 mg per day divided twice daily) for 12 or 24 weeks in adult patients with chronic GT1 HCV infection with or without compensated liver cirrhosis who are also infected with HIV-1. Study patients were either new to therapy (treatment naïve) or had failed previous treatment with pegylated interferon and RBV (treatment-experienced), had a stable immune status (CD4+ counts of ≥200 cells/mm3 or CD4+ % ≥14%) and had HIV-1 ribonucleic acid levels suppressed on a stable atazanavir- or raltegravir-based antiretroviral HIV therapy.

No patients discontinued treatment due to adverse events in either the 12-week or 24-week arm. In the 12-week arm, no virologic breakthroughs were observed while on treatment. One patient (3.3 percent) experienced post-treatment relapse after 12 weeks of treatment. In the 24-week treatment arm, one virologic breakthrough was observed (3.1 percent). Two patients in the 24-week treatment group were believed to have been re-infected post-treatment by a different strain of HCV than the original infection. The most commonly reported adverse events (greater than 15 percent in both treatment arms combined) were fatigue (47.6 percent), insomnia (19 percent), nausea (17.5 percent), and headache (15.9 percent). Elevations in total bilirubin were the most common laboratory abnormality (68.3 percent), were mainly composed of indirect bilirubin, and were not associated with aminotransferase elevations. Reductions in RBV dose because of anemia or reduced hemoglobin occurred in 9.5 percent of patients (n=6/63); all six patients achieved SVR12.

About CORAL-I

CORAL-I is an ongoing Phase 2, multi-center, two-cohort, open-label study evaluating the efficacy and safety of AbbVie's all-oral, interferon-free investigational treatment combining three direct-acting antivirals (ombitasvir/ABT-450/ritonavir and dasabuvir) with RBV (RBV dosing left up to the discretion of the investigator) for 24 weeks in adult non-cirrhotic (screening biopsy Metavir score ≤F2) liver transplant recipients with recurrent chronic GT1 HCV infection. Patients in the study initiated therapy at least 12 months after receiving a liver transplant, had not received other HCV therapy since their liver transplant, and were on a stable immunosuppressant regimen based on either tacrolimus or cyclosporine, for which dose adjustments were advised. Enrollment in the second cohort of the study is ongoing.

One patient (2.9 percent) discontinued the study due to adverse events but still achieved SVR12. Two patients experienced serious adverse events. The most commonly reported treatment-emergent adverse events (greater than 20 percent) were fatigue (50 percent), headache (44.1 percent), cough (32.4 percent), anemia (29.4 percent), diarrhea (26.5 percent), insomnia (26.5), asthenia (23.5 percent), nausea (23.5 percent), muscle spasms (20.6 percent), and rash (20.6 percent). No patients experienced virologic breakthrough while on treatment; however, one patient experienced post-treatment relapse. Nine patients had a grade 2 reduction in hemoglobin, and one patient had a grade 3 reduction. Five patients with hemoglobin decreases (anemia) received a medication to boost their red blood cell production at the investigator's discretion. No patients discontinued study drugs because of anemia, required a blood transfusion, or experienced a rejection of their transplanted liver.

About AbbVie's Investigational Three Direct-Acting Antiviral Treatment

AbbVie's investigational treatment consists of the fixed-dose combination of ABT-450/ritonavir (150/100mg) co-formulated with ombitasvir (25mg), dosed once daily, and dasabuvir (250mg) dosed twice daily with or without ribavirin. The combination of three direct-acting antivirals, each with a distinct mechanism of action, targets and inhibits specific hepatitis C virus proteins in the viral replication process.

About AbbVie's HCV Clinical Development Program

The AbbVie HCV clinical development program is intended to advance scientific knowledge and clinical care by investigating interferon-free, all-oral treatments with and without ribavirin with the goal of achieving high sustained virologic response rates in as many patients as possible. AbbVie's multinational program using an investigational treatment combining three direct-acting antivirals includes more than 2,300 patients in over 25 countries. The program is designed to identify ways to maximize response rates in a broad spectrum of patient populations, including those with compensated cirrhosis, liver transplant recipients and those with human immunodeficiency virus type 1 co-infection.

ABT-450 was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors. ABT-450 is being developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of hepatitis C.

AbbVie's New Drug Application to the U.S. Food and Drug Administration (FDA) and Marketing Authorization Applications to the European Medicines Agency (EMA) for its investigational, all-oral, interferon-free regimen for the treatment of adult patients with chronic genotype 1 HCV infection have been accepted and granted priority review by the FDA and validated and granted accelerated assessment by the EMA.

Safety Information for Ribavirin and Ritonavir

Ribavirin and ritonavir are not approved for the investigational use discussed above, and no conclusions can or should be drawn regarding the safety or efficacy of these products for this use.

There are special safety considerations when prescribing these drugs in approved populations.

Ritonavir must not be used with certain medications due to significant drug-drug interactions and in patients with known hypersensitivity to ritonavir or any of its excipients.

Ribavirin monotherapy is not effective for the treatment of chronic hepatitis C virus and must not be used alone for this use. Ribavirin causes significant teratogenic effects and must not be used in women who are pregnant or breast-feeding and in men whose female partners are pregnant. Ribavirin must not be used in patients with a history of severe pre-existing cardiac disease, severe hepatic dysfunction or decompensated cirrhosis of the liver, autoimmune hepatitis, hemoglobinopathies, or in combination with peginterferon alfa-2a in HIV/HCV co-infected patients with cirrhosis and Child-Pugh score ≥6.

See approved product labels for more information.

About AbbVie

AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases. AbbVie employs approximately 25,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit www.abbvie.com. Follow @abbvieon Twitter or view careers on our Facebook or LinkedIn page.

SOURCE AbbVie

AASLD - BMS Announces High Cure Rates With daclatasvir (DCV) in combination with sofosbuvir (SOF)

BMS Announces High Cure Rates for Hepatitis C Drug
Mon, 11/10/2014 - 10:42am

Bristol-Myers Squibb 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, 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 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 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.

Source: Bristol-Myers Squibb

AASLD- Achillion Reports 100% SVR12 With ACH-3102 and Sovaldi

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 Million IU/ml at Baseline -

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

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.