Pivotal Phase 3 Data from Boehringer Ingelheim Hepatitis C Portfolio to be Presented at 64th Annual AASLD Meeting

October 01, 2013

For U.S. Media Only

Ridgefield, CT, October 1, 2013 – New data from Boehringer Ingelheim’s hepatitis C virus (HCV) clinical development program have been accepted for presentation at the 64^th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), also known as The Liver Meeting^®, taking place November 1-5 in Washington, D.C.

Presentations will include data from several studies evaluating Boehringer Ingelheim’s investigational compound, faldaprevir, including final results from the STARTVerso^™ 1, 2 and 3 pivotal trial programs (NCT01343888, NCT01297270, NCT01358864) in treatment-naïve and treatment-experienced patients. End-of-treatment results from STARTVerso 4™ (NCT01399619) evaluating HIV/HCV co-infected patients will also be presented.

Additionally, data will be presented from studies evaluating drug-drug interactions of faldaprevir with common birth control and anti-addiction medications, as well as a study evaluating faldaprevir pharmacokinetics, safety, and tolerability in patients with renal impairment. Final results from SOUND-C3 (NCT01132313), a Phase 2b study from Boehringer Ingelheim’s interferon-free development program, will also be presented.

Together these studies explore the use of Boehringer Ingelheim’s investigational HCV compounds in a broad range of patients with HCV, in addition to helping understand the potential for interactions with several commonly used medications. Also, they offer insight into the clinical profile of the compounds for researchers and healthcare professionals looking for potential new treatment options for patients with HCV.

“We are pleased to see the presentation of the final results from STARTVerso^™ 1, 2 and 3, Boehringer Ingelheim’s pivotal Phase 3 program in our hepatitis C portfolio, as well as other important analyses evaluating various patient subgroups at this year’s AASLD meeting,” said Peter Piliero, M.D., Vice President, Clinical Development and Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. “These data, combined with that of our interferon-free trial, SOUND-C3, are evidence of our commitment to researching new therapeutic options for patients infected with HCV.”

Faldaprevir and deleobuvir are investigational compounds and not approved by the FDA. Their safety and efficacy have not been established.

Boehringer Ingelheim’s abstracts can be accessed on the AASLD website today at www.aasld.org.

Poster Presentations

 

Title	Lead Author	Presentation Details
Effect of multiple oral doses of faldaprevir on the multiple dose pharmacokinetics of a combination oral tablet of ethinylestradiol and levonorgestrel in healthy premenopausal female volunteers	J. Sabo	ID# 482 Session: HCV Therapy: The Developmental Pipeline Date: Sat, Nov. 2 Time: 2:00 PM – 7:30 PM ET Location: Poster Hall
Mass balance, metabolic profile and the role of hepatic and bacterial enzymes in the metabolism of the HCV polymerase inhibitor, deleobuvir (BI 207127)	R. Sane	ID# 491 Session: HCV Therapy: The Developmental Pipeline Date: Sat, Nov. 2 Time: 2:00 PM – 7:30 PM ET Location: Poster Hall
Pharmacokinetics, safety, and tolerability of faldaprevir in patients with different levels of renal impairment	F. Huang	ID# 466 Session: HCV Therapy: The Developmental Pipeline   Date: Sat, Nov. 2 Time: 2:00 PM – 7:30 PM ET Location: Poster Hall
Effect of steady-state faldaprevir on the pharmacokinetics of steady-state methadone and buprenorphine/naloxone in subjects on stable addiction management therapy	D. Joseph	ID# 483 Session: HCV Therapy: The Developmental Pipeline Date: Sat, Nov. 2 Time: 2:00 PM – 7:30 PM ET Location: Poster Hall
A pooled analysis of two randomized, double-blind placebo-controlled Phase III trials (STARTVerso1&2) of faldaprevir plus pegylated interferon alfa-2a and ribavirin in treatment-naïve patients with chronic hepatitis C genotype-1 infection	D. Jensen	ID# 1088 Session: HCV Therapeutics: New Agents Date: Sun, Nov. 3 Time: 8:00 AM – 5:30 PM ET Location: Poster Hall
Subgroup analyses and baseline predictors of response with faldaprevir plus pegylated interferon alfa-2a and ribavirin in treatment-naïve patients with chronic hepatitis C genotype-1 infection: a pooled analysis of STARTVerso1 and 2	E.M. Yoshida	ID# 1114   Session: HCV Therapeutics: New Agents   Date: Sun, Nov. 3 Time: 8:00 AM – 5:30 PM ET Location: Poster Hall
STARTVerso3: A randomized, double-blind, placebo-controlled Phase III trial of faldaprevir in combination with pegylated interferon alfa-2a and ribavirin in treatment-experienced patients with chronic hepatitis C genotype-1 infection	I. Jacobson	ID# 1100   Session: HCV Therapeutics: New Agents   Date: Sun, Nov. 3 Time: 8:00 AM – 5:30 PM ET Location: Poster Hall
Interferon-Free Treatment with Faldaprevir, Deleobuvir (BI 207127) and Ribavirin in SOUND-C3: 95% SVR12 in HCV-GT1b	J.F. Dufour	ID# 1102   Session: HCV Therapeutics: New Agents   Date: Sun, Nov. 3 Time: 8:00 AM – 5:30 PM ET Location: Poster Hall
STARTVerso 4 Phase III trial of faldaprevir plus peg interferon alfa-2a and ribavirin (PR) in patients with HIV and HCV genotype 1 coinfection: end of treatment response	J. Rockstroh	ID# 1099   Session: HCV Therapeutics: New Agents Date: Sun, Nov. 3 Time: 8:00 AM – 5:30 PM ET Location: Poster Hall
Pharmacokinetic interactions of Faldaprevir and Deleobuvir (BI 207127) and their individual and combined effect on selected cytochrome P450 (CYP) probe substrates in genotype 1 hepatitis C infected patients	C. Cooper	ID# 1083   Session: HCV Therapeutics: New Agents   Date: Sun, Nov. 3 Time: 8:00 AM – 5:30 PM ET Location: Poster Hall

About Boehringer Ingelheim in Hepatitis C Virus (HCV)
In partnership with the scientific community, our clinical trial program is rigorously designed to find answers to the challenges that HCV patients face, including those who are the most difficult to treat. Our pivotal HCV clinical trials for faldaprevir and deleobuvir are comprised of two multi-trial programs, STARTVerso^™ and HCVerso^®.

Faldaprevir, also known as BI 201335, is an investigational, oral protease inhibitor that is specifically designed to target viral replication in the liver. Boehringer Ingelheim is developing faldaprevir as a core component of both interferon-based and interferon-free hepatitis C treatment regimens. STARTVerso^™ is a multi-study Phase 3 trial program that evaluates faldaprevir combined with PegIFN/RBV. The four trials that make up this program study the combination in treatment-naïve, treatment-experienced and HIV co-infected patients with chronic genotype-1 HCV. Deleobuvir, also known as BI 207127, is an investigational NS5B non-nucleoside polymerase inhibitor that has shown the potential to eliminate interferon from HCV treatment when combined in a regimen with faldaprevir and RBV. Phase 2 trials of this interferon-free regimen have been completed and Phase 3 HCVerso® trials investigating this regimen are now underway. As part of our long-term commitment to HCV, the company is exploring other combinations of investigational HCV compounds that work in complementary ways. The recent collaboration of Boehringer Ingelheim with Presidio Pharmaceuticals, Inc. for a Phase 2a clinical study investigating an interferon- and ribavirin-free, all-oral combination is part of the company’s continued commitment to discover and develop innovative options for the treatment of HCV.

STARTVerso^™ and HCVerso^® are registered service marks of Boehringer Ingelheim International GmbH.

The Liver Meeting^® is a registered trademark of the American Association for the Study of Liver Diseases (AASLD).

Hepatitis C is a blood-born infectious disease and a leading cause of chronic liver disease, transplant and failure that affects as many as 150 million people globally. In the United States, an estimated 4.1 million Americans have been infected with HCV, of which approximately 3.2 million have chronic HCV infection. Since 1999 there has been a significant increase in deaths due to chronic HCV, which accounts for 10,000-12,000 deaths in the United States per year.

About Boehringer Ingelheim
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.

The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 140 affiliates and more than 46,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.

Social responsibility is a central element of Boehringer Ingelheim’s culture. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim’s endeavors.

For more information please visit www.us.boehringer-ingelheim.com

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Idenix Pharmaceuticals Announces Nucleotide Prodrug Program Poster Presentation at the American Association for the Study of Liver Diseases (AASLD) Annual Meeting

October 1, 2013

CAMBRIDGE, Mass., Oct. 1, 2013 (GLOBE NEWSWIRE) -- Idenix Pharmaceuticals, Inc. (Nasdaq:IDIX), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today announced a poster presentation featuring preclinical data for its uridine nucleotide prodrug candidate for the treatment of hepatitis C virus (HCV) infection at the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), which will take place in Washington, DC, November 1-5, 2013. Full abstracts can now be viewed at the AASLD website at www.aasld.org.

The following abstract will be presented in a poster session during the AASLD Annual Meeting in the Poster Hall on Saturday, November 2, 2013, 2:00pm — 7:30pm Eastern Time:

• Abstract No. 485: "A Novel Uridine Nucleotide Prodrug, IDX20963, and Its Potential for Use in a Low-Dose Direct-Acting Antiviral Regimen for HCV."

ABOUT HEPATITIS C

Hepatitis C virus is a common blood-borne pathogen infecting three to four million people worldwide annually. The World Health Organization (WHO) estimates that more than 170 million people worldwide are chronically infected with HCV, representing a nearly 5-fold greater prevalence than human immunodeficiency virus.

ABOUT IDENIX

Idenix Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts, is a biopharmaceutical Company engaged in the discovery and development of drugs for the treatment of human viral diseases.  Idenix's current focus is on the treatment of patients with hepatitis C infection.  For further information about Idenix, please refer to www.idenix.com.

Source: Idenix Pharmaceuticals

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Bristol-Myers Squibb to Present Range of New Hepatitis C Data at the 2013 American Association for the Study of Liver Diseases (AASLD) Annual Meeting

• Phase III SVR24 data on daclatasvir + asunaprevir, an investigational, interferon-free and ribavirin-free treatment regimen, in Japanese HCV patients with high unmet needs selected to lead off this year’s Presidential Plenary session
• Data presentations provide further insight on dosing, tolerability and safety of multiple daclatasvir-based investigational HCV regimens
• 16 accepted abstracts on HCV and HBV underscore the breadth of the company’s hepatitis portfolio

Tuesday, October 1, 2013 11:46 am EDT  

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) announced today that 16 abstracts have been accepted for presentation at The Liver Meeting^® 2013, the 64th Annual Meeting of The American Association for the Study of Liver Diseases (AASLD), in Washington D.C., November 1 – 5. These abstracts include new data supporting the company’s broad pipeline of hepatitis C (HCV) compounds.

Key presentations include:

• Results from a Phase III study of an all-oral combination of daclatasvir (DCV) and asunaprevir (ASV) in Japanese HCV genotype 1b patients who are either ineligible or intolerant to interferon-based therapies or who are non-responders to both interferon and ribavirin. This is the first presentation of a Phase III study evaluating an all-oral, interferon-free and ribavirin-free regimen. Presentation of complete SVR₂₄ results from this study will lead the Viral Hepatitis Presidential Plenary session on Tuesday, November 5.
• Additional dosing, safety and efficacy data on DCV, ASV and BMS-791325, several BMS investigational HCV compounds that are being studied as a fixed-dose combination.
• Findings from health economics and outcomes research studies including long-term morbidity and mortality in chronic hepatitis C patients in the U.S. Veterans Health Administration; and an analysis of the burden of alfa-interferon based therapies on chronic hepatitis C patients in Japan.

“The wealth of Bristol-Myers Squibb data at this year’s AASLD meeting reflects our long-standing commitment to researching the unmet medical needs of patients with hepatitis C. We are particularly excited about our investigational, all-oral regimen of daclatasvir and asunaprevir and its potential for HCV patients, including many in Japan who currently have no treatment options,” said Brian Daniels, MD, senior vice president, Global Development and Medical Affairs, Research and Development, Bristol-Myers Squibb. “Just 25 years after the discovery of the hepatitis C virus, the HCV research community is on the cusp of a cure for more patients than ever before. Bristol-Myers Squibb is proud to be among the companies standing at the forefront of this major shift in the treatment paradigm.”

Bristol-Myers Squibb is studying a broad portfolio of new compounds in hopes of providing flexible treatment options which aim to help address the diverse unmet medical needs of a global HCV patient population. These investigational compounds include DCV, ASV, BMS-791325, and peginterferon lambda-1a (Lambda). The company also continues to study the full potential of Baraclude^® (entecavir), an oral antiviral agent with selective activity against HBV. Baraclude is a leading treatment for chronic hepatitis B and is approved in more than 90 countries.

The complete list of Bristol-Myers Squibb data presentations is below. Abstracts can be accessed on the AASLD website at www.aasld.org/livermeeting.

 

Title			Date/Time
Hepatitis C: Direct-Acting Antiviral Data
Presidential Plenary: All-oral Combination of Daclatasvir plus Asunaprevir in Interferon Ineligible Naive/Intolerant and Nonresponder Japanese Patients Chronically Infected with HCV Genotype 1b: Results from a Phase III Trial			Tuesday, November 5, 8 – 8:15 a.m.
Asunaprevir Pharmacokinetics and Safety in Subjects With Impaired Renal Function			Saturday, November 2, 5:30 p.m. – 7:00 p.m.
Lack of Pharmacokinetic Interaction Between the HCV Protease Inhibitor MK-5172 and HCV NS5A Inhibitor Daclatasvir In Normal Healthy Volunteers
No Clinically-Relevant Interactions Between Asunaprevir and Selective Serotonin Reuptake Inhibitors (Escitalopram and Sertraline) in Healthy Subjects
Daclatasvir Pharmacokinetics in Healthy Subjects: No Clinically-Significant Drug-Drug Interactions with Cyclosporine or Tacrolimus			Sunday, November 3, 12:30 p.m. – 2 p.m.
Analysis of HCV Resistance Variants in a Phase III Trial of Daclatasvir Combined With Asunaprevir for Japanese Patients with Genotype 1b Infection
Safety and Efficacy of BMS-791325, a Non-Nucleoside NS5B Polymerase Inhibitor, Combined with Peginterferon Alfa-2a and Ribavirin in Treatment-Naïve Patients Infected with Hepatitis C Virus Genotype 1
Hepatitis C and B: PEG-Interferon Lambda Data
Inverse Modulation in Hepatic Expression of Interferon Receptor Complexes for Alpha and Lambda during HCV Infection are Associated with Altered Interferon Signaling Induction upon Treatment with Peginterferon Alfa-2a Compared to Peginterferon Lambda-1a			Saturday, November 2, 5:30 p.m. – 7 p.m.
Safety Profile of Peginterferon Lambda for Treatment of Chronic Hepatitis B Virus (HBV) or Chronic Hepatitis C Virus (HCV) Infection: Cross-Study Analysis of Patients Treated in Three Phase 2 Studies			Sunday, November 3, 12:30 p.m. – 2 p.m.
Hepatitis C: Outcomes Research / Real-World Data
Impact of Treatment on Long-Term Morbidity and Mortality in Chronic Hepatitis C Patients Receiving Care Through the U.S. Veterans Health Administration			Tuesday, November 5, 12:30 p.m. – 12:45 p.m.
Using Laboratory Data to Predict Long-Term Morbidity and Mortality in Chronic Hepatitis C Patients Through The U.S. Veterans Health Administration			Tuesday, November 5, 10:30 a.m. – 12 p.m.
Patient Burden of Peginterferon Alfa (Alfa)-Based Therapy Among Patients with Chronic Hepatitis C Infection in Japan: Report from a 2013 National Survey Study
The Comparative Effectiveness of Daclatasvir Plus Asunaprevir vs Telaprevir Triple Therapy in Nonresponder Japanese Patients Chronically Infected With HCV Genotype 1b: Results from a Bayesian Meta-Analysis
A Meta-Analysis Platform for the Continuous Updating of Knowledge Regarding Treatment Regimens for Hepatitis C Virus Infection
Chronic Hepatitis B: BARACLUDE (entecavir) Clinical Data
The Safety and Efficacy of Entecavir and Tenofovir Combination Therapy for Chronic Hepatitis B in Patients with Previous Nucleos(t)ide Treatment Failure			Sunday, Nov. 3, 8 a.m. – 5:30 p.m.
Entecavir Pharmacokinetics Among Nucleos/tide-Naїve Pediatric Subjects

About Bristol-Myers Squibb’s Commitment to Liver Disease

Bristol-Myers Squibb’s hepatitis C pipeline includes compounds with different mechanisms of action, pursuing both biologics as well as small molecule direct-acting antivirals. These compounds are being studied as part of multiple treatment regimens with the goal of increasing SVR rates across diverse patient types and geographies.

• Our investigational NS5A replication complex inhibitor daclatasvir (DCV) has been extensively studied in thousands of patients to date as a foundational agent for multiple DAA-based combination therapies and is currently in Phase III development. DCV has shown antiviral potency and pan-genotypic activity across HCV genotypes in vitro. DCV has a drug-drug interaction profile that supports its continued study in a variety of HCV combination regimens
• Asunaprevir (ASV) is an NS3 protease inhibitor in Phase III development for hepatitis C as a component of DCV-based treatment regimens
• BMS-791325 is a non-nucleoside inhibitor of the NS5B polymerase, currently in Phase II development for hepatitis C as a component of DCV-based treatment regimens
• Lambda is an investigational type III interferon that has the potential to offer an alternative to alfa-interferon in patients for whom an interferon-based regimen is required or preferred

About Hepatitis C

Hepatitis C is a virus that infects the liver and is transmitted through direct contact with infected blood and blood products. An estimated 170 million people worldwide are infected with hepatitis C, with genotype 1 being the most prevalent genotype. Up to 90 percent of those infected with hepatitis C will not clear the virus and will become chronically infected. According to the World Health Organization, 20 percent of people with chronic hepatitis C will develop cirrhosis and, of those, up to 25 percent may progress to liver cancer. In Japan, the hepatitis C virus is the most common cause of chronic hepatitis and cirrhosis, and approximately 1.2 million people there are living with the hepatitis C virus.

INDICATION and IMPORTANT SAFETY INFORMATION about BARACLUDE (entecavir) 0.5mg/1mg Tablets:

INDICATION

BARACLUDE (entecavir) is indicated for the treatment of chronic hepatitis B virus (HBV) infection in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.

The following points should be considered when initiating BARACLUDE:

1. This indication is based on histologic, virologic, biochemical, and serologic responses in nucleoside-treatment-naïve and lamivudine-resistant adult subjects with HBeAg-positive or HBeAg-negative chronic HBV infection and compensated liver disease.

2. Virologic, biochemical, serologic, and safety data are available from a controlled study in adult subjects with chronic HBV infection and decompensated liver disease.

3. Virologic, biochemical, serologic, and safety data are available for a limited number of adult subjects with HIV/HBV co-infection who have received prior lamivudine therapy.

IMPORTANT SAFETY INFORMATION

WARNINGS: SEVERE ACUTE EXACERBATIONS OF HEPATITIS B, PATIENTS CO-INFECTED WITH HIV AND HBV, and LACTIC ACIDOSIS AND HEPATOMEGALY

• Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy, including entecavir. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

• Limited clinical experience suggests there is a potential for the development of resistance to HIV (human immunodeficiency virus) nucleoside reverse transcriptase inhibitors if BARACLUDE is used to treat chronic HBV infection in patients with HIV infection that is not being treated. Therapy with BARACLUDE is not recommended for HIV/HBV co-infected patients who are not also receiving highly active antiretroviral therapy (HAART).

• Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues, alone or in combination with antiretrovirals.

Warnings and Precautions

• Before initiating BARACLUDE (entecavir) therapy, HIV antibody testing should be offered to all patients. BARACLUDE has not been studied as a treatment for HIV infection and is not recommended for this use.

• Lactic acidosis with BARACLUDE use has been reported, often in association with hepatic decompensation, other serious medical conditions, or drug exposures. Patients with decompensated liver disease may be at higher risk for lactic acidosis. BARACLUDE should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity.

Adverse Reactions

• In clinical trials in patients with compensated liver disease, the most common (≥3%) adverse reactions of any severity with at least a possible relation to study drug for BARACLUDE-treated subjects were headache, fatigue, dizziness, and nausea. In these trials, the most common adverse reactions of moderate to severe intensity (grades 2-4) were diarrhea, dyspepsia, nausea, vomiting, fatigue, headache, dizziness, somnolence, and insomnia.

• In the decompensated liver disease trial, the most common adverse reactions of any severity among patients treated with BARACLUDE (entecavir), regardless of causality, included: peripheral edema (16%), ascites (15%), pyrexia (14%), hepatic encephalopathy (10%), and upper respiratory infection (10%). In this trial, 18% (18/102) of BARACLUDE patients and 20% (18/89) of adefovir patients died during the first 48 weeks of therapy. The majority of those deaths were due to liver related causes.

Drug Interactions

BARACLUDE is primarily eliminated by the kidneys, therefore coadministration of BARACLUDE with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of either BARACLUDE or the coadministered drug. Patients should be monitored closely when receiving BARACLUDE with other renally-eliminated drugs.

Pregnancy and Nursing Mothers

• There are no adequate and well-controlled studies of BARACLUDE (entecavir) in pregnant women. BARACLUDE should be used during pregnancy only if clearly needed and after careful consideration of the risks and benefits.

• There are no studies on the effect of BARACLUDE on transmission of HBV from mother to infant. Therefore, appropriate interventions should be used to prevent neonatal acquisition of HBV.

• It is not known whether BARACLUDE is excreted into human milk; however, many drugs are excreted into breast milk. Due to the potential for serious adverse reactions in nursing infants from BARACLUDE, risks and benefits should be considered when deciding whether to discontinue breast-feeding or discontinue BARACLUDE in nursing women.

Pediatric Use

• Safety and effectiveness of BARACLUDE in pediatric patients below the age of 16 years have not been established.

Renal Impairment

• Dosage adjustment of BARACLUDE is recommended for patients with a creatinine clearance <50 mL/min, including those on hemodialysis or continuous ambulatory peritoneal dialysis.

Liver Transplant Recipients

• Renal function must be carefully monitored both before and during treatment with BARACLUDE in a liver transplant recipient who has received or is receiving an immunosuppressant that may affect renal function, such as cyclosporine or tacrolimus.

Dosage and Administration

BARACLUDE (entecavir) should be administered on an empty stomach (at least 2 hours after a meal and at least 2 hours before the next meal).

The recommended dose of BARACLUDE:

• in nucleoside-naïve adults and adolescents (16+ yrs) with compensated liver disease is 0.5 mg once daily

• in adults and adolescents (16+ yrs) with compensated liver disease, and refractory to lamivudine or with known lamivudine or telbivudine resistance mutations (rtM204I/V with or without rtL180M, rtL80I/V, or rtV173L) is 1 mg once daily

• in adults with decompensated liver disease is 1 mg once daily

The optimal duration of treatment with BARACLUDE (entecavir) for patients with chronic HBV infection and the relationship between treatment and long-term outcomes such as cirrhosis and hepatocellular carcinoma are unknown.

Additional Information

BARACLUDE is not a cure for HBV. Patients should be advised that treatment with BARACLUDE has not been shown to reduce the risk of transmission of HBV to others through sexual contact or blood contamination.

Please see accompanying Full Prescribing Information, including Boxed WARNINGS click here.

About Bristol-Myers Squibb

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

Bristol-Myers Squibb Forward Looking Statement

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that the clinical trials of these compounds will support regulatory filings, or that the compounds described in this release will receive regulatory approvals or, if approved, that they will become commercially successful products. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2012, in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.

BARACLUDE^® (entecavir) is a registered trademark of Bristol-Myers Squibb Company

Contact:

Bristol-Myers Squibb
Media:
Carrie Fernandez, 609-252-4831
carrie.fernandez@bms.com
Julie Ferguson, 609-252-5597
julie.ferguson@bms.com
or
Investors:
Ranya Dajani, 609-252-5330
ranya.dajani@bms.com
Ryan Asay, 609-252-5020
ryan.asay@bms.com

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AbbVie To Present Investigational Data From Phase II Hepatitis C Program At The Liver Meeting

PHASE III TOP-LINE RESULTS EXPECTED BEGINNING LATER IN 2013

Oct 1, 2013

NORTH CHICAGO, Ill., Oct. 1, 2013 /PRNewswire/ -- AbbVie (NYSE: ABBV) announced that new data from its phase II hepatitis C clinical development program will be presented at The Liver Meeting, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Washington, D.C., November 1-5, 2013. In total, eight abstracts will be presented, four of which include additional analyses from the phase IIb AVIATOR study. The data examine sustained virologic response (SVR) concordance, patient adherence to the regimen, patient reported outcomes and the impact of ribavirin dose reduction.  

The Liver Meeting will precede AbbVie's reporting of initial results from the pivotal phase III clinical trials of the safety and efficacy of AbbVie's investigational triple direct-acting antiviral (DAA) regimen for the treatment of hepatitis C. Reporting of those results is expected to begin later this year.

"At AbbVie, we are committed to researching new therapies that maximize sustained virologic response  with the hope of providing much needed new options for people with hepatitis C," said Barry Bernstein, M.D., vice president, infectious disease development, AbbVie. "We are very encouraged as we await top-line results from our phase III program, which we will share later this year."

Additionally, the oral presentation at AASLD will provide results from the PEARL-I study evaluating an interferon- and ribavirin-free, two-DAA investigational regimen in genotype 1b treatment-naïve patients and prior null responders. AbbVie is also investigating drug combinations for additional genotypes and next generations of DAAs as part of their ongoing commitment to the HCV community.

A brief summary of AbbVie's abstract titles is presented below.

About AbbVie's HCV Development Program
The AbbVie HCV clinical development program is intended to advance scientific knowledge by investigating an interferon-free, all-oral DAA regimen with the goal of producing high SVR rates in as many patients as possible, including those typically most difficult to cure. The large, multinational HCV program includes more than 2,200 patients from 30 countries.

AbbVie's hepatitis C portfolio includes investigational medicines with three different mechanisms of action targeting areas of the viral replication process including boosted protease inhibitor (ABT-450), polymerase (ABT-333) inhibitor and NS5A (ABT-267) inhibitor, currently being studied in clinical trials. ABT-450/r is co-formulated with ABT-267.

Details of AbbVie's phase III clinical programs are as follows:

 

Study	Patients (n)	Treatment Regimen	Treatment Duration
SAPPHIRE I	GT1, treatment-naïve (600*)	• ABT450/r +ABT267** • ABT333 • Ribavirin	12 weeks
SAPPHIRE II	GT1, treatment-experienced (400*)	• ABT450/r +ABT267** • ABT333 • Ribavirin	12 weeks
PEARL II	GT1b, treatment-experienced (210*)	• ABT450/r +ABT267** • ABT333 • Ribavirin	12 weeks
		•ABT450/r +ABT267** ABT333	12 weeks
PEARL III	GT1b, treatment-naïve (400*)	• ABT450/r +ABT267** • ABT333 • Ribavirin	12 weeks
		•  ABT450/r +ABT267** • ABT333	12 weeks
PEARL IV	GT1a, treatment-naive (300*)	• ABT450/r +ABT267** • ABT333 • Ribavirin	12 weeks
		•  ABT450/r +ABT267** • ABT333	12 weeks
TURQUOISE II	GT1, treatment-naïve and treatment-experienced (with compensated cirrhosis) (300*)	• ABT450/r +ABT267** • ABT333 • Ribavirin	12 weeks
		• ABT450/r +ABT267** • ABT333 • Ribavirin	24 weeks

*projected study population
**ABT-267 is co-formulated with ABT-450/r

In May of 2013, AbbVie's investigational DAA regimen with and without ribavirin for HCV genotype 1 was designated as a Breakthrough Therapy by the U.S. Food and Drug Administration (FDA). This designation is intended to help expedite the development of drugs for serious or life-threatening conditions and is based in part on preliminary clinical evidence demonstrating a drug or regimen may have substantial improvement on at least one clinically significant endpoint compared to available therapy.

AbbVie Hepatitis C Data at AASLD 2013

• Trends in Liver-Related Healthcare Resource Utilization for HCV-Infected Individuals in the US: 2002-2010
  Poster #367
  November 2^nd, 2:00PM ET; Poster Hall
  This study analyzed years 2002-2010 of the National Inpatient Sample (NIS) data set of hospital admissions from the Healthcare Cost and Utilization Project (HCUP) to determine the number of adult (age 20+ years) liver-related hospital admissions occurring in HCV-infected patients (identified by ICD-9 codes).

• Interferon- and Ribavirin-free Regimen of ABT-450/r + ABT-267 in HCV Genotype 1b-infected Treatment-Naïve Patients and Prior Null Responders
  Oral Presentation: Parallel Session 75
  November 3^rd, 5:15PM ET; Hall E
  This oral presentation includes data from the phase IIb PEARL-I study, which examines an interferon-free, ribavirin-free investigational regimen of ABT-450/r plus ABT-267 in 82 patients with HCV genotype 1b.

• Low Relapse Rate Leads to High Concordance of SVR4 and SVR12 with SVR24 After Treatment with ABT-450/r, ABT-267, ABT-333 + Ribavirin in Patients with Chronic HCV Genotype 1 Infection in the AVIATOR Study
  Poster #1089
  November 3^rd, 8:00AM ET; Poster Hall
  This study evaluated the concordance of SVR24 with rapid virologic response (RVR), SVR4 and SVR12 in treatment groups from the phase IIb AVIATOR study in 247 patients.

• High Medication Adherence in HCV-Infected Patients Taking a Triple-DAA Regimen for 12 Weeks
  Poster #1096
  November 3^rd, 8:00AM ET; Poster Hall
  This study presents medication adherence data based on electronic compilation of drug dosing history among 327 patients receiving the investigational triple-DAA regimen plus ribavirin for 8, 12 or 24 weeks.

• Health-Related Quality of Life (HRQoL), Health State, Function and Wellbeing of Chronic HCV Patients Treated with Interferon-Free, Oral DAA Regimens: Patient Reported Outcome (PRO) Results from the AVIATOR Study
  Poster #1113
  November 3^rd, 8:00AM ET; Poster Hall
  This intent-to-treat analysis from the phase IIb AVIATOR study includes patient reported outcomes (PRO) in patients receiving 12-week, ribavirin-containing investigational triple-DAA regimen.

• Safety of Ribavirin-containing Regimens of ABT-450/r, ABT-333, and ABT-267 for the Treatment of HCV Genotype 1 Infection and Efficacy in Subjects with Ribavirin Dose Reductions
  Poster #1118
  November 3^rd, 8:00AM ET; Poster Hall
  This study examined the safety of a ribavirin-containing, investigational triple-DAA, interferon-free regimen and the effects of ribavirin dose reductions on treatment response.

• HCV RNA "Target Detected" after "Target Not Detected" During IFN-Free Treatment: Time to Worry or Not?
  Poster #1125
  November 3^rd, 8:00AM ET; Poster Hall
  This study examined the frequency of TDANs (Target Detected After Not Detected) and the likelihood of subsequent virologic failure in subjects from the phase IIb AVIATOR study treated with ABT- 450/r plus ABT-267 plus ABT-333 plus ribavirin for 12 or 24 weeks in treatment naïve and null responders. 

• Adherence to Interferon-containing Therapy Among Veteran Affairs Hepatitis C Patients
  Poster #1909
  November 5^th, 8:00AM ET; Poster Hall
  Data from the United States Veterans Health Administration (VHA) Medical SAS Dataset (years 2008 to 2011) were used in this analysis.

The list of accepted abstracts for The Liver Meeting can be accessed on www.aasld.org.

ABT-450 was discovered during the course of the ongoing collaboration between AbbVie and Enanta Pharmaceuticals 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 HCV.

About the Hepatitis C Virus
Across the world, about 160 million people are chronically infected with hepatitis C.[1] Hepatitis C is an inflammation of the liver caused by an infection with the hepatitis C virus (HCV).[2] HCV is transmitted when an infected person's blood enters the bloodstream of another person.[3]

For the hepatitis C virus, there are six major HCV genotypes (GT1-6).^[4] Presently, there is no vaccine for the hepatitis C virus (HCV) infection.³ Decision to treat is dependent on a number of factors such as the amount of liver damage present, other conditions the patient may have, amount of virus in the body, and viral genotype.⁴ If treatment is needed, a hepatitis C infection is typically treated with a combination of antivirals.³

About AbbVie
AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott. With its 125-year history, 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. In 2013, AbbVie employs approximately 21,000 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 @abbvie on Twitter or view careers on our Facebook or LinkedIn page.

1. Lavanchy D. Evolving epidemiology of hepatitis C virus. Clin Microbiol Infect. 2011; 17(2):107-15.
2. World Health Organization. Global Alert and Response (GAR): Hepatitis C. 2003. http://www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index1.html. Accessed April 9, 2013.
3. World Health Organization. Hepatitis C Fact Sheet 2012. http://www.who.int/mediacentre/factsheets/fs164/en/ Accessed April 9, 2013.
4. European Association for the Study of the Liver. Clinical Practice Guidelines: Management of hepatitis C virus infection. Journal of Hepatology. 2011; 55: 245–264.

SOURCE AbbVie Inc.

For further information: Media: Elizabeth Hoff, +1 (847) 935-4236; Javier Boix, +1 (847) 937-6113; Or Investor Relations: Elizabeth Shea, +1 (847) 935-2211

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Data from Merck’s Investigational Hepatitis C Treatment Portfolio to be Presented at the 64th American Association for the Study of Liver Diseases Annual Meeting

Tuesday, October 1, 2013 10:00 am EDT

WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the presentation of data from studies evaluating the company’s investigational oral chronic hepatitis C virus (HCV) treatments MK-5172 and MK-8742 at the 64^th American Association for the Study of Liver Diseases Annual Meeting (AASLD). The meeting is scheduled to take place in Washington, D.C., Nov. 1-5, 2013.

“Merck is committed to developing HCV therapies that have the potential to offer new options for a broad range of patient types,” said Dr. Eliav Barr, vice president, Infectious Diseases, Merck Research Laboratories. “We continue to build upon our strong legacy in HCV and look forward to sharing the latest clinical data for our investigational HCV therapies, MK-5172 and MK-8742.”

MK-5172 is an investigational, once-daily, oral HCV NS3/4A protease inhibitor currently in Phase IIB development. MK-8742 is an investigational, once-daily, oral HCV NS5A replication complex inhibitor currently in Phase IIB development. Both candidates are being evaluated in broad clinical programs that include investigations in various HCV segments, multiple HCV genotypes and patients who have previously failed prior therapy.

Selected presentations of clinical data for MK-5172 and MK-8742

• High Efficacy and Safety of the All-Oral Combination Regimen, MK-5172/MK-8742 +/- RBV for 12 Weeks in HCV Genotype 1 Infected Patients: The C-WORTHY Study. Lawitz, E., et al. Oral Presentation #76: Sunday, Nov. 3, 2013, 5:30-5:45 p.m.
• Kinetic Analyses of Antiviral Suppression by NS5A Inhibitors Reveal Early and Potent Inhibition of Viral Assembly and Release. McGivern, D.R., et al. Oral Presentation #78: Sunday, Nov. 3, 2013, 6:00-6:15 p.m.
• High Efficacy at Lower Doses of MK-5172 25mg and 50mg Daily for 12 weeks in HCV Genotype (G) 1 Treatment-Naïve Non-Cirrhotic Patients. Vierling, J., N et al. Poster #1123. Sunday, Nov. 3, 2013, 8:00 a.m. to 5:30 p.m.
• Efficacy and Safety of an Interferon-Free Regimen of MK-5172 + Ribavirin for 12 Weeks or 24 Weeks in Treatment-Naïve, Non-Cirrhotic Subjects with HCV GT1 Infection: The C-SPIRIT Study. Gane, E.J., et al., Poster #1110. Sunday, Nov. 3, 2013, 8:00 a.m. to 5:30 p.m.
• MK-8742, a HCV NS5A Inhibitor with a Broad Spectrum of HCV Genotypic Activity, Demonstrates Potent Antiviral Activity in Genotype-1 and -3 HCV-Infected Patients. Yeh, W. W., et al. Poster #479. Saturday, Nov. 2, 2013, 2:00-7:30 p.m.

The abstracts were published today and can be accessed on the AASLD website. For program information, please visit: http://www.aasld.org/livermeeting/program/Pages/default.aspx

About Merck

Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebook and YouTube.

Forward-Looking Statement

This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of Merck’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; Merck’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of Merck’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck’s 2012 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

Revatio^® and Adcirca^® are trademarks of their respective owners and are not trademarks of Merck & Co., Inc., Whitehouse Station, N.J., USA.

Contact:

Merck
Media:
Sarra Herzog, 908-423-6154
or
Investor:
Carol Ferguson, 908-423-4465
Justin Holko, 908-423-5088

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Medivir announces that Simeprevir data will be presented at the upcoming AASLD meeting

Stockholm, Sweden — Medivir AB (OMX: MVIR) announced that data will be presented on the investigational protease inhibitor simeprevir for the treatment of genotype 1 chronic hepatitis C in adult patients with compensated liver disease at the upcoming Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), which will take place November 1 to 5 in Washington, D.C.

The data to be presented at the 2013 AASLD Annual Meeting include:

Poster Presentations: HCV Therapeutics: New Agents, Poster Hall, November 3, 8:00 a.m. - 5:30 p.m. (EST):

• Simeprevir (TMC435) with peg-interferon α-2a/ribavirin for treatment of chronic HCV genotype 1 infection in patients who relapsed after previous interferon-based therapy: Efficacy and safety in patient sub-populations in the PROMISE Phase III trial
• Lead Author: Xavier Forns, Hospital Clinic, Barcelona, Spain

• Adding simeprevir to peginterferon/ribavirin for HCV shortens time with patient-reported symptoms and impairment in quality of life: Results from the simeprevir Phase III QUEST 1, QUEST 2, and PROMISE studies
• Lead Author: Jane A. Scott, Janssen

• Simeprevir (TMC435) with peginterferon/ribavirin for treatment of chronic HCV genotype 1 infection in treatment-naïve patients: Efficacy in difficult-to-treat patient sub-populations in the QUEST-1 and 2 Phase III trials
• Lead Author: Ira M. Jacobson, Weill Cornell Medical College, New York, USA

• Resistance analyses of HCV isolates from patients treated with simeprevir in Phase 2b/3 studies
• Lead Author: Oliver Lenz, Janssen

Full session details and data presentation listings for the 2013 AASLD Annual Meeting can be found at http://www.aasld.org/livermeeting.

For more information please contact:
Rein Piir, EVP Corporate Affairs & IR
Mobile: +46 708 537 292.

About simeprevir
Simeprevir is an investigational NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB for the treatment of genotype 1 chronic hepatitis C in adult patients with compensated liver disease, including all stages of liver fibrosis. Simeprevir works by blocking the protease enzyme that enables the hepatitis C virus to replicate in host cells.

For additional information about simeprevir clinical trials, please visit www.clinicaltrials.gov.

About Medivir
Medivir is an emerging research-based pharmaceutical company focused on infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company’s key pipeline asset is simeprevir, a novel protease inhibitor for the treatment of hepatitis C that is being developed in collaboration with Janssen R&D Ireland. Medivir has also a broad product portfolio with prescription pharmaceuticals in the Nordics.

For more information about Medivir AB, please visit the Company’s website: www.medivir.com

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Novel HCV therapy leads to rapid response

By: DENISE NAPOLI, Family Practice News Digital Network

10/01/13

Combination therapy with the second-generation protease inhibitor danoprevir yielded high rates of sustained virologic response in hepatitis C.

Moreover, a large portion of patients also demonstrated an extended rapid virologic response up to 20 weeks, reported Dr. Patrick Marcellin and his colleagues in the October issue of Gastroenterology.

Dr. Marcellin, of the Hôpital Beaujon in Clichy, France, and his coinvestigators looked at 225 treatment-naive adults with hepatitis C virus (HCV) genotype 1 infection, including those who had a serum RNA level of 50,000 IU/mL or more.

Exclusion criteria included advanced fibrosis or cirrhosis, anemia, poorly controlled diabetes, or body mass index less than 18 kg/m² or greater than 36 kg/m².

The goal of this phase II, randomized, placebo-controlled study (ATLAS) was to evaluate the efficacy of treatment with danoprevir plus peginterferon alfa-2a/ribavirin for 12 weeks, compared with peginterferon alfa-2a/ribavirin alone.

Patients were randomized to one of three doses of oral danoprevir or placebo: 300 mg every 8 hours, 600 mg every 12 hours, or 900 mg every 12 hours.

All doses and placebo were given with standard combination HCV therapy, including subcutaneous peginterferon alfa-2a 180 mg/week plus oral ribavirin (1,000 mg/day for patients with a body weight less than 75 kg or 1,200 mg/day for patients weighing 75 kg or more).

At week 12, treatment with danoprevir or placebo was stopped, and peginterferon alfa-2a/ribavirin was continued for a total duration of 24 or 48 weeks, according to patient response.

Dr. Marcellin found that by week 1, mean decreases in HCV RNA ranged from 3.95 to 4.28 log₁₀ IU/mL in the danoprevir groups, compared with 0.77 log₁₀ IU/mL in the placebo group.

By week 2, according to the investigators, more than half of the danoprevir patients and none of the placebo recipients had achieved undetectable HCV RNA levels.

Indeed, broken down by dose, the researchers calculated that 74% of the danoprevir 300-mg group achieved a rapid virologic response (undetectable serum HCV RNA at week 4), with 65% maintaining an extended rapid virologic response (eRVR), defined as an undetectable HCV RNA that lasted from weeks 4 through 20.

Among the patients taking 600-mg doses, 88% achieved an RVR, with 79% maintaining an eRVR at week 20.

Finally, 86% of patients in the 900-mg treatment group achieved an RVR, although only 18% reached an eRVR.

Patients with an eRVR stopped all treatment at 24 weeks.

"Relapse occurred in 18%, 8%, and 11% of patients treated with danoprevir 300 mg, 600 mg, and 900 mg, respectively, versus 38% in the placebo group," the authors wrote.

Looking at the side-effect profile, Dr. Marcellin reported that fatigue, headache, nausea, insomnia, myalgia, and chills were the most common adverse events for both the treatment and placebo groups.

They also observed reversible, grade 4 elevations in alanine aminotransferase (ALT) levels between weeks 6 and 12 in 2% of danoprevir-treated patients, including three in the 900-mg cohort and one in the 600-mg cohort.

Treatment was discontinued, and serum ALT levels returned to within 1.5 times the upper limit of normal within a month for all four patients, the authors added.

"Notwithstanding the low incidence of reversible ALT elevations observed with high-dose danoprevir in this trial, danoprevir also appears to have a better tolerability profile than either boceprevir or telaprevir, as evidenced by the lower incidence of rash and anemia among danoprevir-treated patients compared with placebo recipients," concluded the investigators.

Indeed, they pointed to other studies showing that coadministration of low-dose ritonavir, another protease inhibitor, "significantly inhibits danoprevir reactive metabolite formation, proposed to be associated with ALT elevations."

"Studies to further evaluate the efficacy and safety of danoprevir in different patient groups are ongoing," the researchers said.

Dr. Marcellin and his fellow investigators reported financial relationships with numerous pharmaceutical companies, including Roche, the maker of danoprevir, which also funded this study.

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Danoprevir's role still unclear

Second-generation protease inhibitors (PIs) currently in development are generally thought to have less drug-drug interactions, improved dosing schedules, as well as less frequent and less severe side effects. Many of the second-generation PIs are macrocyclic molecules, which have been shown to generally be more potent and, depending on the location of the macrocycle, able to retain activity against resistant variants. Common wild-type and drug-resistant variants of the NS3 protein include Q80K, R155K, V36M/R155K, A156T, and D168A (ACS Chem. Biol. 2013;8:1469-78). They have also shown increased efficacy against genotype 1, though they still have limited efficacy against other genotypes (Curr. Gastroenterol. Rep. 2013;15:303 [doi: 10.1007/s11894-012-0303-3]).

This report on danoprevir clearly shows it is a potent, pan-genotypic, macrocyclic second-generation PI that meets all of these criteria. However, the grade 4 elevations in alanine aminotransferase (ALT) levels seen in 2% of danoprevir-treated patients (including three in the 900-mg cohort and one in the 600-mg cohort) that were seen in this study became a major roadblock to the phase III development of the compound. Instead, the coadministration of low-dose ritonavir, another protease inhibitor, which significantly inhibits danoprevir reactive metabolite formation, has allowed the compound to move forward into advanced studies without the hepatotoxicity concern [J. Hepatol. 2012;56(Suppl 2):S467; Hepatology 2012;56(Suppl 1):552A; Hepatology 2012;56(Suppl 1):231A; J. Hepatol. 2012;56(Suppl 2):S555].

The role for a ritonavir-boosted PI in all-oral interferon-free regimens remains to be defined over the coming years. This is not the only PI that requires boosting (ABT450); however, the field is quickly becoming crowded with PIs that do not require ritonavir (asunaprevir, faldaprevir, simeprevir, and vaniprevir). The role for danoprevir in the United States is therefore still unclear.

Dr. Paul J. Pockros is director of the Liver Disease Center of the division of gastroenterology/hepatology at the Scripps Clinic, director of the Scripps Clinic Liver Research Consortium, and director of clinical research at the Scripps Translational Science Institute, La Jolla, Calif. He is a researcher, speaker, and advisory board member for Roche/Genentech.

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Also See: Randomized Controlled Trial of Danoprevir Plus Peginterferon Alfa-2a and Ribavirin in Treatment-Naïve Patients With Hepatitis C Virus Genotype 1 Infection