AbbVie Presents Late-Breaking, Preliminary Phase 3b Data with VIEKIRAX® + EXVIERA® in Chronic Hepatitis C Patients with Renal Impairment at The International Liver Congress™ 2015

- RUBY-I evaluates treatment-naïve, non-cirrhotic, genotype 1 chronic hepatitis C patients with severe renal impairment
- In preliminary data from RUBY-I, patients receiving VIEKIRAX + EXVIERA with or without ribavirin who reached post-treatment week four (n=10 of 20 enrolled) achieved 100 percent sustained virologic response at four weeks post-treatment (SVR4)1
- AbbVie's Phase 3b studies explore VIEKIRAX + EXVIERA in additional patient populations seen in clinical practice and across multiple countries around the world

VIENNA, April 25, 2015 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced new, preliminary safety and efficacy data from the first cohort of its ongoing, Phase 3b RUBY-I study. RUBY-I is evaluating VIEKIRAX® (ombitasvir/paritaprevir/ritonavir tablets) + EXVIERA® (dasabuvir tablets) with or without ribavirin (RBV) in treatment-naïve, non-cirrhotic, genotype 1 (GT1) chronic hepatitis C patients with severe renal impairment (stage 4 or 5), including those on hemodialysis. The primary endpoint of the study is the percentage of patients achieving sustained virologic response at 12 weeks post-treatment (SVR₁₂). Patients who reached post-treatment week four to date (n=10 of 20 enrolled) achieved 100 percent SVR₄ (n=10/10).¹ RUBY-I was presented as a late-breaker today at The International Liver Congress™ (ILC) 2015, the 50^th annual meeting of the European Association for the Study of the Liver (EASL) in Vienna, Austria.

"Treating hepatitis C patients with severe renal impairment may be a concern, particularly in those patients on hemodialysis," said Paul J. Pockros, M.D., director of Liver Disease Center Scripps Clinic and director of clinical research at Scripps Translational Science Institute in La Jolla, California. "With limited data currently available on the safety and efficacy of interferon-free treatments for patients with renal impairment, the preliminary results seen in RUBY-I show promising initial SVR rates with the VIEKIRAX + EXVIERA regimen in a dedicated study for this often difficult-to-treat patient population."

Additionally, RUBY-I data showed no virologic failures to date.¹ Preliminary safety analyses reported that patients experienced mainly mild or moderate adverse events when receiving VIEKIRAX + EXVIERA with or without RBV, most commonly (>20 percent) anemia, fatigue, diarrhea, nausea, dizziness and headache.¹ To date, eight of 13 genotype 1a (GT1a) patients had a RBV dose interruption.¹

"RUBY-I is part of AbbVie's broader Phase 3b program and demonstrates our continued focus on people living with hepatitis C that have specific needs," said Scott Brun, M.D., vice president, pharmaceutical development, AbbVie. "Studies in our Phase 3b program will help to further expand our knowledge of the utility of VIEKIRAX + EXVIERA in special populations encountered in clinical practice."

Additional Phase 3b studies from AbbVie presented at ILC 2015 included MALACHITE-I and MALACHITE-II data, and the TOPAZ-I and TOPAZ-II study design. The MALACHITE studies evaluate adult patients with GT1 chronic HCV infection without cirrhosis receiving VIEKIRAX + EXVIERA with or without RBV compared to treatment with telaprevir with pegylated-interferon and RBV, which remains the standard of care in many regions of the world.^2,3 The TOPAZ studies will evaluate the effect of SVR₁₂ on long-term outcomes, five years following treatment with VIEKIRAX + EXVIERA with or without RBV in adults with GT1 chronic HCV infection.⁴

About RUBY-I Study
RUBY-I is an ongoing, multi-center, open-label Phase 3b study with two cohorts that evaluates the safety and efficacy of 12 or 24 weeks of treatment with VIEKIRAX® + EXVIERA® with or without ribavirin, based on sub-genotype in treatment-naïve, adult patients with genotype 1 (GT1) chronic hepatitis C virus infection who have severe renal impairment (pre-dialysis; stage 4 chronic kidney disease) or end-stage renal disease (on hemodialysis; stage 5 chronic kidney disease) with or without compensated cirrhosis.¹ Cohort 1 consists of 20 patients without cirrhosis and cohort 2 will evaluate approximately 20 patients with or without compensated cirrhosis. Ribavirin was started at 200mg once daily for all genotype 1a (GT1a)- infected patients and dosed four hours prior to the start of GT1a patients on hemodialysis. Additional study results, including cohort 2, will be disclosed at future scientific congresses.

About VIEKIRAX® + EXVIERA®
VIEKIRAX + EXVIERA is approved in the European Union for the treatment of genotype 1 (GT1) chronic hepatitis C virus (HCV) infection, including patients with compensated cirrhosis. VIEKIRAX is approved in the European Union for the treatment of genotype 4 (GT4) chronic HCV infection.

VIEKIRAX consists of the fixed-dose combination of paritaprevir 150mg (NS3/4A protease inhibitor) and ritonavir 100mg with ombitasvir 25mg (NS5A inhibitor), dosed once daily, and EXVIERA consists of dasabuvir 250mg (non-nucleoside NS5B polymerase inhibitor) dosed twice daily taken with or without ribavirin (RBV), dosed twice daily based on patient type. VIEKIRAX + EXVIERA is taken for 12 weeks with or without RBV, except in GT1a and GT4 patients with compensated cirrhosis, who should take it for 24 weeks with RBV.

Paritaprevir was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for hepatitis C protease inhibitors and regimens that include protease inhibitors. Paritaprevir has been developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of chronic hepatitis C.

Additional information about AbbVie's hepatitis C development program can be found on www.clinicaltrials.gov.

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 or without ribavirin with the goal of achieving high sustained virologic response rates in as many patients as possible. AbbVie's global Phase 3b program plans to include more than 2,800 genotype 1 patients in over 200 study centers worldwide, including the U.S., Canada, Europe, Russia and Brazil. Data in patients with severe renal impairment, including patients on hemodialysis, will be presented at ILC. Additionally, AbbVie's Phase 3b HCV program includes studies in patients with decompensated and compensated cirrhosis. Data from these studies will be presented at future scientific congresses.

Additional information about AbbVie's hepatitis C development program can be found on www.clinicaltrials.gov.

VIEKIRAX® + EXVIERA® EU Indication
VIEKIRAX is indicated in combination with other medicinal products for the treatment of chronic hepatitis C (CHC) in adults. EXVIERA is indicated in combination with other medicinal products for the treatment of chronic hepatitis C (CHC) in adults.

Important EU Safety Information
Contraindications:
VIEKIRAX + EXVIERA are contraindicated in patients with severe hepatic impairment (Child-Pugh C). Patients taking ethinyl estradiol-containing medicinal products must discontinue them and switch to an alternative method of contraception prior to initiating VIEKIRAX + EXVIERA. Do not give VIEKIRAX with certain drugs that are sensitive CYP3A substrates or strong inhibitors of CYP3A. Do not give VIEKIRAX and EXVIERA with strong or moderate enzyme inducers. Do not give EXVIERA with certain drugs that are strong inhibitors of CYP2C8.

Special warnings and precautions for use:
VIEKIRAX and EXVIERA are not recommended as monotherapy and should be used in combination with other medicinal products for the treatment of hepatitis C infection.

Pregnancy and concomitant use with ribavirin
When VIEKIRAX + EXVIERA are used in combination with ribavirin, women of childbearing potential or their male partners must use an effective form of contraception during the treatment and 6 months after the treatment. Refer to the Summary of Product Characteristics for ribavirin for additional information.

ALT elevations
Transient elevations of ALT to >5x ULN without concomitant elevations of bilirubin occurred in clinical trials with VIEKIRAX + EXVIERA and were more frequent in a subgroup who were using ethinyl estradiol-containing contraceptives.

Use with concomitant medicinal products
Use caution when administering VIEKIRAX with fluticasone or other glucocorticoids that are metabolized by CYP3A4. A reduction in colchicine dosage or interruption in colchicine is recommended in patients with normal renal or hepatic function. VIEKIRAX with or without EXVIERA is expected to increase exposure of statins so certain statins need to be discontinued or dosages reduced. Low dose ritonavir, which is part of VIEKIRAX, may select for PI resistance in HIV co-infected patients without ongoing antiretroviral therapy. HIV co-infected patients without suppressive antiretroviral therapy should not be treated with VIEKIRAX.

Adverse Reactions
Most common (>20 percent) adverse reactions for VIEKIRAX + EXVIERA with RBV were fatigue and nausea.

Full summary of product characteristics is available at www.ema.europa.eu

Globally, prescribing information varies; refer to the individual country product label for complete 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 more than 26,000 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.

Forward-Looking Statements
Some statements in this news release may be forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry.

Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," in AbbVie's 2014 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

References:
¹ Pockros P, et al. Safety Of Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir For Treating HCV GT1 Infection In Patients With Severe Renal Impairment Or End-stage Renal Disease: The RUBY-I Study. Presented at the 50th International Liver Congress (ILC); April 22-26; Vienna, Austria 
² Conway B, et al. MALACHITE-I: Phase 3b Trial Of Ombitasvir/Paritaprevir/R And Dasabuvir +/-Ribavirin Or Telaprevir + Peginterferon/Ribavirin In Treatment-naïve Adults With HCV Genotype 1. Abstract presented at the 50th International Liver Congress (ILC); April 22-26; Vienna, Austria
³ Dore G, et al. MALACHITE-II: Phase 3b Trial Of Ombitasvir/Paritaprevir/R And Dasabuvir + Ribavirin Or Telaprevir + Peginterferon/Ribavirin In Peginterferon/Ribavirin Treatment-experienced Adults With HCV Genotype 1. Abstract presented at the 50th International Liver Congress (ILC); April 22-26; Vienna, Austria 
⁴ Dumas E, et al. Phase 3b Studies To Assess Long-term Clinical Outcomes In HCV GT1-infected Patients Treated With Ombitasvir/Paritaprevir/Ritonavir And Dasabuvir With Or Without Ribavirin. Abstract presented at the 50th International Liver Congress (ILC); April 22-26; Vienna, Austria.

SOURCE AbbVie

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Merck Announces Presentation of Phase 2 Clinical Trial Results of Investigational Chronic Hepatitis C Therapy Grazoprevir/Elbasvir at the International Liver Congress™ 2015

Results of C-SALVAGE Study Showed High Sustained Virologic Response Rates in Patients Who Failed Prior Combination Therapy with Certain Direct Acting Antiviral (DAA) Agents

Results of C-SWIFT Study Provide Proof-of-Concept for Shorter Than Twelve Weeks Duration of Treatment with Triple-DAA Regimen in Patients with Chronic Hepatitis C Virus (HCV) Genotypes 1 and 3 Infection

Saturday, April 25, 2015 9:00 am EDT

VIENNA – April 25, 2015 – Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the presentation of results from two Phase 2 clinical trials evaluating the safety and efficacy of the company’s investigational once-daily treatment regimen of grazoprevir (100mg) and elbasvir (50mg)[1] in adult patients with chronic hepatitis C virus (HCV) infection. Treatment with grazoprevir and elbasvir in combination with ribavirin (RBV) (C-SALVAGE trial) showed high rates of sustained virologic response 12 weeks after the completion of treatment (SVR12) in patients with chronic HCV genotype 1 (GT1) infection with or without liver cirrhosis who previously failed combination therapy with a DAA agent. In addition, final results from the C-SWIFT study evaluating grazoprevir/elbasvir in combination with sofosbuvir 400mg in treatment-naïve patients with or without liver cirrhosis chronically infected with HCV GT1 or GT3 were presented as proof-of-concept for potentially shortening HCV treatment duration below 12 weeks. Data from these studies were presented at The International Liver Congress^TM 2015 – the 50^th annual congress of the European Association for the Study of the Liver.

“We continue to advance our Phase 3 clinical program for grazoprevir/elbasvir evaluating diverse patient populations with chronic HCV infection, including those widely considered among the most difficult to treat,” said Dr. Eliav Barr, vice president, infectious diseases, Merck Research Laboratories. “Findings from these Phase 2 studies formed part of the basis for our decision to rapidly advance our large and comprehensive clinical development program that incorporates studies dedicated to patient populations with specific unmet medical needs.”

C-SALVAGE Overview and Findings

C-SALVAGE (Abstract #O001) is a Phase 2, single arm, open label clinical trial conducted to evaluate the efficacy and safety of 12 weeks of treatment with grazoprevir and elbasvir plus RBV in patients with chronic HCV GT1 infection who have previously failed treatment with peginterferon and RBV combined with a DAA (boceprevir, simeprevir or telaprevir). Of the 79 patients who received one or more doses of grazoprevir and elbasvir, 43 percent had liver cirrhosis. 

Following 12 weeks of treatment with a combination of grazoprevir and elbasvir plus RBV, 96 percent of the patients (76/79) with chronic HCV GT1 infection who had failed prior treatment with specified DAA-based regimens achieved SVR12. Ninety four percent (32/34) of patients with compensated cirrhosis achieved SVR12. Virologic failure was reported for three patients in the trial. All three patients had resistance associated variants at baseline and relapsed after completion of study treatment.

The most common adverse events included fatigue (28%), headache (19%), asthenia (15%) and nausea (12%). Five serious adverse events were reported, none of which were considered related to study drug. One patient discontinued treatment due to an adverse event that was not considered to be drug-related. Detailed findings of the study were recently posted online in the “Articles in Press” section of the Journal of Hepatology, the official journal of the European Association for the Study of the Liver.

C-SWIFT Overview and Findings

C-SWIFT (Abstract #O006) is a proof-of-concept Phase 2 open label clinical trial conducted to evaluate the efficacy and safety of grazoprevir/elbasvir plus sofosbuvir over shorter treatment durations. Specifically, treatment-naïve patients with or without liver cirrhosis chronically infected with HCV GT1 were treated for 4, 6 or 8 weeks and treatment-naïve patients with or without liver cirrhosis chronically infected with HCV GT3 were treated for 8 or 12 weeks. Interim findings were previously presented at the 65^th American Association for the Study of Liver Diseases in November 2014.

SVR12 results by treatment arm in the modified intent to treat population are shown above (table 1).  Among GT1 patients, virologic relapse occurred in 20 non-cirrhotic patients receiving four weeks of treatment, in four non-cirrhotic and four cirrhotic patients receiving six weeks of treatment, and in one cirrhotic patient receiving eight weeks of treatment. Among GT3 patients, virologic relapse occurred in one non-cirrhotic patient receiving eight weeks of treatment, and in one cirrhotic patient receiving 12 weeks of treatment. There were no reported cases of virologic breakthrough.

No patients discontinued due to treatment-related adverse events. The most common adverse events reported across all treatment groups and genotypes were headache (4% overall, range 2-8% across treatment arms), fatigue (2% overall, range 0-8% across treatment arms) and nausea (2% overall, range 2-8% across treatment arms). Two serious adverse events – pyelonephritis and B-cell lymphoma – were reported but were not considered to be related to study medicine.

About Grazoprevir/Elbasvir

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

Merck’s Commitment to HCV

For nearly 30 years, Merck has been at the forefront of the response to the HCV epidemic. Merck employees are dedicated to applying their scientific expertise, resources and global reach to deliver innovative health care solutions that support people living with HCV worldwide.

About Merck

Today’s Merck is a global health care leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care 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 U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of Merck’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and 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 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 except as required by applicable law. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck’s 2014 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

[1] Grazoprevir is a HCV NS3/4A protease inhibitor and elbasvir is a HCV NS5A replication complex inhibitor

CONTACTS:

Merck Media: Doris Li (908) 246-5701

or

Sarra Herzog (201) 669-6570

Investor: Joe Romanelli (908) 740-1986

or

Justin Holko (908) 740-1879

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

97% of post-transplant patients with HCV genotype 1a achieved cure

91% of post-transplant patients with HCV genotype 3 achieved cure 

No need seen to alter existing transplantation medication regimens

Saturday, April 25, 2015 10:00 am EDT

Dateline:

PRINCETON, N.J., APRIL 25, 2015

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

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

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

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

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

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

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

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

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

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

About ALLY-1: Study Design

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

About Hepatitis C

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

About Bristol-Myers Squibb’s HCV Portfolio

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

Daclatasvir was approved in Europe in August 2014 for use in combination with other medicinal products across genotypes 1, 2, 3 and 4 for the treatment of chronic hepatitis C virus (HCV) infection in adults. Beyond Europe, it is approved in Japan, as well as multiple countries in Latin and South America, the Middle East and Asia Pacific. Additionally, the U.S. FDA currently is reviewing a New Drug Application (NDA) for the use of daclatasvir and sofosbuvir to treat patients with HCV genotype 3.

About Bristol-Myers Squibb

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

Bristol-Myers Squibb Forward Looking Statement

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that daclatasvir will receive regulatory approval in the United States, or if approved, that it will become a commercially successful product. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2014, 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.

Contact:

Media:
Robert Perry, Office: 609-419-5378, Cell: 407-492-4616, rob.perry@bms.com

Investors:
Ranya Dajani, 609-252-5330, ranya.dajani@bms.com

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Gilead Announces Results From Studies Evaluating Sofosbuvir-Based Regimens in Chronic Hepatitis C Patients With Genotypes 2-5

-- High Cure Rates Observed Across a Range of Genotypes --

VIENNA, Austria--(BUSINESS WIRE)--Apr. 25, 2015-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced results from two studies evaluating the safety and efficacy of investigational uses of sofosbuvir-based regimens in chronic hepatitis C virus (HCV)-infected patients with genotypes 2, 3, 4 and 5. Results from the BOSON study of Sovaldi^® (sofosbuvir 400 mg) in combination with ribavirin (RBV) or with pegylated interferon (PEG)/RBV demonstrated high cure rates across all patients with genotypes 2 and 3. Separately, results from a Phase 2 study demonstrate the safety and efficacy of Harvoni^® (ledipasvir 90 mg/sofosbuvir 400 mg) in patients with genotypes 4 or 5 infection. Data from both studies will be presented in oral sessions at the 50th Annual Meeting of the European Association for the Study of the Liver (The International Liver Congress™ 2015) in Vienna, Austria.

Sovaldi and Harvoni are each approved in the United States for the treatment of chronic HCV infection. Sovaldi is used in combination with other agents and its efficacy has been established in patients with genotypes 1-4; Harvoni is indicated for patients with genotype 1.

BOSON (Study GS-US-334-0153, #LB05), a randomized Phase 3 study of 592 patients, evaluated the safety and efficacy of Sovaldi plus RBV for 16 or 24 weeks compared with Sovaldi plus PEG/RBV for 12 weeks among treatment-naïve or treatment-experienced genotype 3 patients with and without cirrhosis and treatment-experienced genotype 2 patients with cirrhosis. Thirty-seven percent of study participants had cirrhosis.

Among genotype 3 patients, rates of sustained virologic response 12 weeks after treatment (SVR12) were highest among those receiving Sovaldi plus PEG/RBV for 12 weeks (93 percent, n=168/181), compared to those receiving Sovaldi plus RBV for 24 weeks (84 percent, n=153/182) or for 16 weeks (71 percent, n=128/181). Treatment-experienced genotype 3 patients with cirrhosis receiving Sovaldi plus PEG/RBV demonstrated SVR12 rates of 86 percent (30/35).

Genotype 2 patients also demonstrated high SVR12 rates across all treatment arms. SVR12 rates among patients receiving Sovaldi plus PEG/RBV were 94 percent (15/16), and 100 percent (17/17) and 87 percent (13/15) for those receiving Sovaldi plus RBV for 24 and 16 weeks, respectively.

Sovaldi plus PEG/RBV and Sovaldi plus RBV were well tolerated. The most common adverse events in the study were fatigue, headache, insomnia and nausea. Overall, six patients (1 percent) discontinued treatment due to adverse events, one of whom was treated with Sovaldi plus PEG/RBV.

“It remains difficult to achieve a virological response in genotype 3, which is one of the most prevalent genotypes in the world, with higher prevalence in Europe and Asia,” said Graham R. Foster, FRCP, PhD, Professor of Hepatology, The Liver Unit, Queen Mary's University of London, Barts Health, London, United Kingdom. “These results are compelling because they represent the highest cure rates observed among treatment-experienced, cirrhotic genotype 3 patients in any Phase 3 clinical trial to date.”

In a separate open-label Phase 2 study of Harvoni conducted in France (Study GS-US-337-1119, O056), results demonstrated high SVR rates in both treatment-naïve and treatment-experienced patients with chronic HCV genotypes 4 or 5 infection, 50 percent of whom had cirrhosis.

Ninety-three percent of patients with genotype 4 (41/44) and 95 percent of patients with genotype 5 (39/41) achieved SVR12. Response rates were similar among both treatment-naïve and -experienced patients and regardless of cirrhosis.

The most common adverse events (affecting more than 10 percent of patients) were asthenia, headache and fatigue. Most adverse events were mild or moderate in severity and none resulted in treatment discontinuation. There were no grade 3 or 4 clinical laboratory abnormalities.

“HCV genotype 4 and 5 are less prevalent than other genotypes and therefore, have traditionally not been closely studied,” said Armand Abergel, MD, PhD, Department of Hepatology and Gastroenterology, Centre Hospitalier Universitaire-Estaing, Université d'Auvergne, Clermont-Ferrand, France. “These data provide important evidence that the all-oral, ribavirin-free Harvoni regimen is both safe and effective for many patients with genotype 4 or 5, regardless of prior treatment experience.”

The safety and efficacy of these investigational uses of Harvoni and Sovaldi have not been established.

Important Safety Information About Sovaldi

Contraindications

Sovaldi combination treatment with ribavirin or with peginterferon alfa plus ribavirin is contraindicated in women who are pregnant or may become pregnant and men whose female partners are pregnant because of the risk for birth defects and fetal death associated with ribavirin. Contraindications to peginterferon alfa and ribavirin also apply to Sovaldi combination treatment. Refer to the prescribing information of peginterferon alfa and ribavirin for a list of their contraindications.

Warnings and Precautions

Serious Symptomatic Bradycardia When Coadministered with Amiodarone and Another HCV Direct Acting Antiviral (DAA): Amiodarone is not recommended for use with Sovaldi in combination with another DAA due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.

Pregnancy: Use with ribavirin or peginterferon alfa/ribavirin: Ribavirin therapy should not be started unless a report of a negative pregnancy test has been obtained immediately prior to initiation of therapy. Female patients of childbearing potential and their male partners must use two forms of non-hormonal contraception during treatment and for at least 6 months after treatment has concluded. Routine monthly pregnancy tests must be performed during this time. Refer to the prescribing information for ribavirin.

Use with Potent P-gp Inducers: Rifampin and St. John’s wort should not be used with Sovaldi as they may significantly decrease sofosbuvir plasma concentration, reducing its therapeutic effect.

Adverse Reactions

Most common (≥20 percent, all grades) adverse reactions for:

Sovaldi + peginterferon alfa + ribavirin combination therapy were fatigue, headache, nausea, insomnia, and anemia

Sovaldi + ribavirin combination therapy were fatigue, and headache

Drug Interactions

In addition to rifampin and St. John’s wort, coadministration of Sovaldi is not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of sofosbuvir, reducing its therapeutic effect.

Important Safety Information About Harvoni

Warnings and Precautions

Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone: Amiodarone is not recommended for use with Harvoni due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.

Risk of Reduced Therapeutic Effect of Harvoni Due to P-gp Inducers: Rifampin and St. John’s wort are not recommended for use with Harvoni as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.

Related Products Not Recommended: Harvoni is not recommended for use with other products containing sofosbuvir (Sovaldi).

Adverse Reactions

Most common (≥10 percent, all grades) adverse reactions were fatigue and headache.

Drug Interactions

In addition to rifampin and St. John’s wort, coadministration of Harvoni is also not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of ledipasvir and sofosbuvir, reducing the therapeutic effect of Harvoni.

Coadministration of Harvoni is not recommended with simeprevir due to increased concentrations of ledipasvir and simeprevir. Coadministration is also not recommended with rosuvastatin or co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate due to increased concentrations of rosuvastatin and tenofovir, respectively.

Consult the full Prescribing Information for Harvoni for more information on potentially significant drug interactions, including clinical comments.

About Gilead

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. Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California.

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 risk that Gilead may observe unfavorable results from additional clinical trials involving Sovaldi and Harvoni for various patient populations, including those with genotype 2, 3, 4 and 5 HCV. 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 Annual Report on Form 10-K for the year ended December 31, 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 and Harvoni is available at www.gilead.com.

Sovaldi and Harvoni are registered trademarks of Gilead Sciences, Inc., or its related companies.

For more information on Gilead Sciences, please visit the company’s website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

Source: Gilead Sciences, Inc.

Gilead Sciences, Inc.
Sung Lee, +1 650-524-7792 (Investors)
Nathan Kaiser, +1 650-522-1853 (Media)
Michele Rest, +1 650-577-6935 (Media)

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

Public Release: 24-Apr-2015

Researchers suggest an extrahepatic manifestation of hepatitis C may be an increased risk of cancer

European Association for the Study of the Liver

April 24, 2015, Vienna , Austria: Results announced today at The International Liver CongressTM 2015 show that cancer rates in patients with the hepatitis C virus (HCV) were significantly increased compared to the non-HCV cohort. The researchers suggest an extrahepatic manifestation of HCV may be an increased risk of cancer.

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

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

In the HCV cohort there were 2,213 cancer diagnoses (1,524/100,000) during the 5-year period and 1,654 cancer diagnoses when liver cancer was excluded (1,139/100,000). In the non-HCV cohort there were 84,419 cancer diagnoses (605/100,000) during the same 5-year period and 83,795 (601/100,000) when liver cancer was excluded. When all cancers are considered the rate is 2.5 times higher in the HCV cohort; when liver cancers are excluded, the rate is still almost 2 times higher.

Lisa Nyberg, MD, MPH, Kaiser Permanente, Southern California, senior author of the study, explains: "The results suggest that cancer rates are increased in the cohort of hepatitis C patients versus the non-hepatitis C patients, both including and excluding liver cancers. These findings certainly point to the suggestion that hepatitis C may be associated with an increased risk of cancer. However, the findings must be interpreted with caution, as the study also showed that confounding factors such as alcohol abuse, tobacco, obesity, and diabetes modified the results."

Dr Laurent Castera, Vice-Secretary, European Association for the Study of the Liver, commented: "This data adds to the evidence bank linking hepatitis C with an increased risk of cancer, and highlights that there is still a long way to go in order to fully understand this complex and devastating disease."

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About The International Liver Congress™

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

About EASL

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

Contact

For more information, please contact the ILC Press Office at:

ilc.press@easloffice.eu or
+44 (0)20 3580 5444

INCREASED CANCER RATES IN PATIENTS WITH CHRONIC HEPATITIS C: AN ANALYSIS OF THE CANCER REGISTRY IN A LARGE U.S. HEALTH MAINTENANCE ORGANIZATION

Anders H. Nyberg* 1, Joanie W. Chung2, Jiaxiao M. Shi3, T. C. Cheetham3, Kevin M. Chiang4, Reina Haque5, Zobair M. Younossi6, Lisa M. Nyberg1

1Gastroenterology/Hepatology, Kaiser Permanente, San Diego, 2Kaiser Permanete, Research and Evaluation, 3Research and Evaluation, Kaiser Permanente, Pasadena, 4Pharmacy Analytical Services, Kaiser Permanente, Downey, 5Research and Evaluatuion, Kaiser Permanente, Pasadena, 6Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, United States

Background and Aims: Hepatitis C virus (HCV) is an oncogenic virus, and an increased risk of malignancy in HCV has previously been reported. Cancer types associated with HCV include non-Hodgkin's lymphoma, renal and prostate cancers; as well as liver cancer. The aim of this study was to describe cancer rates in our cohort of HCV patients compared to cancer rates in the non-HCV population.

Methods: This is a retrospective study at Kaiser Permanente Southern California (KPSC), a large health maintenance organization with 3.5-4 million members. The KPSC cancer registry is an accredited program maintaining a complete profile of all cancer diagnoses for all KP members. In this study, we recorded all cancer diagnoses in patients ?18 years of age with or without HCV during 2008-2012.

Results: From 2008 to 2012, 145,210 patient years were included in the HCV cohort, and 13,948,826 patient years were included in the non HCV cohort. Mean age at cancer diagnosis in the HCV cohort was 61.8 years, in the non-HCV cohort, 63.5 years. In the HCV cohort there were 2,213 cancer diagnoses (1524/100000) during the 5 year period and 1,654 cancer diagnoses when liver cancer was excluded (1139/100000). In the non HCV cohort there were 84,419 cancer diagnoses (605/100000) during the same 5 year period and 83,795 (601/100000) when liver cancer was excluded. The rate ratios between the HCV and non HCV cohorts for the total number of cancer cases including and excluding liver cancer are shown in Table 1.

Conclusions: In our cohort of Hepatitis C infected patients, cancer rates were significantly increased compared to the non-HCV cohort. This suggests that another extrahepatic manifestation of HCV may be an increased risk of cancer.

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