April 9, 2015

Sci Transl Med 8 April 2015:
Vol. 7, Issue 282, p. 282ra49
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3010286

Research Article

DRUG DISCOVERY

Shanshan He1, Billy Lin1, Virginia Chu1, Zongyi Hu1, Xin Hu2, Jingbo Xiao2, Amy Q. Wang2, Cameron J. Schweitzer1, Qisheng Li1, Michio Imamura3, Nobuhiko Hiraga3, Noel Southall2, Marc Ferrer2, Wei Zheng2, Kazuaki Chayama3, Juan J. Marugan2 and T. Jake Liang1,*

+ Author Affiliations

  1. 1Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  2. 2National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
  3. 3Department of Medicine and Molecular Sciences, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 730-0053, Japan.
  1. *Corresponding author. E-mail: jliang@nih.gov

Abstract

Hepatitis C virus (HCV) infection affects an estimated 185 million people worldwide, with chronic infection often leading to liver cirrhosis and hepatocellular carcinoma. Although HCV is curable, there is an unmet need for the development of effective and affordable treatment options. Through a cell-based high-throughput screen, we identified chlorcyclizine HCl (CCZ), an over-the-counter drug for allergy symptoms, as a potent inhibitor of HCV infection. CCZ inhibited HCV infection in human hepatoma cells and primary human hepatocytes. The mode of action of CCZ is mediated by inhibiting an early stage of HCV infection, probably targeting viral entry into host cells. The in vitro antiviral effect of CCZ was synergistic with other anti-HCV drugs, including ribavirin, interferon-α, telaprevir, boceprevir, sofosbuvir, daclatasvir, and cyclosporin A, without significant cytotoxicity, suggesting its potential in combination therapy of hepatitis C. In the mouse pharmacokinetic model, CCZ showed preferential liver distribution. In chimeric mice engrafted with primary human hepatocytes, CCZ significantly inhibited infection of HCV genotypes 1b and 2a, without evidence of emergence of drug resistance, during 4 and 6 weeks of treatment, respectively. With its established clinical safety profile as an allergy medication, affordability, and a simple chemical structure for optimization, CCZ represents a promising candidate for drug repurposing and further development as an effective and accessible agent for treatment of HCV infection.

  • Copyright © 2015, American Association for the Advancement of Science

Citation: S. He, B. Lin, V. Chu, Z. Hu, X. Hu, J. Xiao, A. Q. Wang, C. J. Schweitzer, Q. Li, M. Imamura, N. Hiraga, N. Southall, M. Ferrer, W. Zheng, K. Chayama, J. J. Marugan, T. J. Liang, Repurposing of the antihistamine chlorcyclizine and related compounds for treatment of hepatitis C virus infection. Sci. Transl. Med. 7, 282ra49 (2015).

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

FOR IMMEDIATE RELEASE

FOR MEDICAL AND TRADE MEDIA ONLY

April 09, 2015 04:00 AM Eastern Daylight Time

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

“We are delighted to present additional data for simeprevir in combination with other currently available therapeutic options alongside early-stage data for our nucleotide portfolio.”

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

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

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

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

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

Late-Breaking Poster Presentations

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

  • A Phase 3, randomised, open-label study to evaluate the efficacy and safety of 12 and 8 weeks of simeprevir (SMV) plus sofosbuvir (SOF) in treatment-naïve and -experienced patients with chronic HCV genotype 1 infection without cirrhosis: The OPTIMIST-1 study1
    • Abstract LP14
    • Lead Author: P. Kwo; Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University, Indianapolis, IN, USA
  • A Phase 3, open-label, single-arm study to evaluate the efficacy and safety of 12 weeks of simeprevir (SMV) plus sofosbuvir (SOF) in treatment-naïve or -experienced patients with chronic HCV genotype 1 infection and cirrhosis: The OPTIMIST-2 study2
    • Abstract LP04
    • Lead Author: E. Lawitz; Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX, USA
  • Simeprevir (SMV) plus daclatasvir (DCV) and sofosbuvir (SOF) in treatment-naïve and -experienced patients with chronic hepatitis C virus genotype 1 or 4 infection and decompensated liver disease: Interim results from the Phase 2 IMPACT study1
    • Abstract LP07
    • Lead Author: E. Lawitz; Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX, USA

Oral Presentation

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

Poster Presentations

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

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

Alios BioPharma Poster Presentations

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

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

About Hepatitis C

Hepatitis C, a blood-borne infectious disease of the liver and a leading cause of chronic liver disease, is a major global public health concern. Approximately 170 million people are infected with hepatitis C worldwide15 and 350,000 people per year die from the disease globally16 with 86,000 deaths in the European region each year.17 When left untreated, hepatitis C can cause significant damage to the liver, including cirrhosis. Additionally, hepatitis C may increase the risk of developing complications from cirrhosis, which may include liver failure.18

About Janssen’s HCV Development Programme

The goal of the Janssen HCV clinical development programme is to provide physicians with multiple treatment options in order to offer patients the best possible chance at successful therapy.

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

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

These compounds are being developed with the express intent of targeting critical steps of the hepatitis C virus replication cycle.

About Simeprevir (OLYSIO®)

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

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

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

About Janssen Pharmaceutical Companies of Johnson & Johnson

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

# # #

This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen R&D Ireland and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in new product development, including the uncertainty of clinical success and of obtaining regulatory approvals; competition, including technological advances, new products and patents attained by competitors; challenges to patents; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and description of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 28, 2014, including in Exhibit 99 thereto, and the company's subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies or Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.

References

1 P Kwo et al. The OPTIMIST-1 study, abstract presented at the European Associate for the Study of the Liver (EASL) 2015.

2 Lawitz M et al. The OPTIMIST-2 study, abstract presented at the European Associate for the Study of the Liver (EASL) 2015.

3 Lawitz M et al. The IMPACT study, abstract presented at the European Associate for the Study of the Liver (EASL) 2015.

4 Forns X et al. The SATURN study, abstract presented at the European Associate for the Study of the Liver (EASL) 2015.

5 Ouwerkerk-Mahadevan, S et al. Abstract presented at the European Associate for the Study of the Liver (EASL) 2015.

6 Fevery, B et al. Abstract presented at the European Associate for the Study of the Liver (EASL) 2015.

7 Alam, I et al. Abstract presented at the European Associate for the Study of the Liver (EASL) 2015.

8 El Raziky, M et al. Abstract presented at the European Associate for the Study of the Liver (EASL) 2015.

9 Asselah, T et al. Abstract presented at the European Associate for the Study of the Liver (EASL) 2015.

10 Tandon, M et al. Abstract presented at the European Associate for the Study of the Liver (EASL) 2015.

11 Forlenza, J.B. et al. Abstract presented at the European Associate for the Study of the Liver (EASL) 2015.

12 Bichoupan, K et al. Abstract presented at the European Associate for the Study of the Liver (EASL) 2015.

13 Jin, Z et al. Abstract presented at the European Associate for the Study of the Liver (EASL) 2015.

14 Tan, H et al. Abstract presented at the European Associate for the Study of the Liver (EASL) 2015.

15 World Health Organisation, Hepatitis C. Available at: http://www.who.int/csr/disease/hepatitis/Hepc.pdf Last accessed April 2015.

16 World Health Organisation. Hepatitis C. Fact sheet N. 164. Available at: http://www.who.int/mediacentre/factsheets/fs164/en/. Last accessed April 2015.

17 Muhlberger M et al. HCV-related burden of disease in Europe: a systematic assessment of incidence, prevalence, morbidity, and mortality. BMC Public Health 2009;9:34.

April 2015
PHGB/HEP/

Contacts

Janssen
Media Contact: Ronan Collins
Mobile: +47 (0) 488 425 00
or
Media Contact: Hans Vanavermaete
Mobile: +32 (0) 478 44 72 78
or
Investor Contact: Lesley Fishman
Office: +1 (732) 524 2524
or
Investor Contact: Louise Mehrotra
Office: +1 (732) 524-6491

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

Apr 8, 2015

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

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

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

Abstracts for AbbVie's HCV Pipeline Compounds:

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

Abstracts for Approved VIEKIRAX and EXVIERA:

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

Abstracts for Phase 3b Program:

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

Abstracts for AbbVie's HCV Investigational Treatment:

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

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

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

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

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, dosed twice daily. 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.

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.

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.

SOURCE AbbVie

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Congress Highlights Include Results from Trials in a Wide Range of HCV Patients -- Patients with Chronic Kidney Disease, HIV Co-infection, Cirrhosis, and Prior Treatment Failures

Company Remains on Track for NDA Filing with the U.S. FDA During First Half of 2015

Wednesday, April 8, 2015 7:00 am EDT

"Our clinical program is among the largest and most comprehensive, with studies dedicated to patient populations where significant unmet medical need still exists, such as prior treatment failures, as well as those living with co-morbid conditions, including HIV infection, chronic kidney disease and individuals on opiate substitution therapy."

KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside of the United States and Canada, today announced that grazoprevir/elbasvir, an investigational single tablet regimen for the treatment of chronic hepatitis C virus (HCV) infection, has received two new Breakthrough Therapy designations from the U.S. Food and Drug Administration (FDA) for the treatment of patients with chronic HCV genotype 4 (GT4) infection, and for the treatment of chronic HCV genotype 1 (GT1) infection in patients with end stage renal disease on hemodialysis. Additionally, the company announced presentations from the broad grazoprevir/elbasvir development program at the upcoming International Liver Congress™. A total of 14 abstracts from studies evaluating grazoprevir/elbasvir are scheduled to be presented, including three from the company’s ongoing Phase 3 pivotal C-EDGE program, one from the pivotal Phase 2b/3 C-SURFER study, and seven from ongoing or completed Phase 2 studies. The range of data to be presented underscores the company’s ongoing commitment to developing an all-oral regimen with wide application across diverse patient populations. The International Liver Congress™ 2015 – the 50th annual congress of the European Association for the Study of the Liver – is scheduled to take place at the Reed Messe Convention Center, Vienna, Austria, from April 22 – 26, 2015.

“HCV remains a global public health epidemic. At Merck, we are focused on the development of an efficacious, well-tolerated, once-daily therapy that can be used to treat multiple genotypes and a diverse population of chronic HCV patients,” said Dr. Eliav Barr, vice president, infectious diseases, Merck Research Laboratories. “Our clinical program is among the largest and most comprehensive, with studies dedicated to patient populations where significant unmet medical need still exists, such as prior treatment failures, as well as those living with co-morbid conditions, including HIV infection, chronic kidney disease and individuals on opiate substitution therapy.”

In October 2013, the FDA granted Breakthrough Therapy designation for grazoprevir/elbasvir for the treatment of patients with chronic HCV genotype 1 (GT1). In January 2015, the FDA notified Merck of its intention to rescind that Breakthrough Therapy designation. The FDA has now granted two new Breakthrough Therapy designations for grazoprevir/elbasvir; the designations are now for the treatment of patients infected with chronic HCV GT1 with end stage renal disease on hemodialysis, and patients infected with chronic HCV genotype 4 (GT4). Breakthrough Therapy designation is intended to expedite the development and review of a candidate that is planned for use, alone or in combination, to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.

At The International Liver Congress 2015™, key data presentations will include:

  • Primary results from the C-EDGE program, Phase 3 clinical trials evaluating grazoprevir/elbasvir (with and without ribavirin) across multiple HCV genotypes (1, 4 and 6) and diverse patient populations, including those difficult to treat, over a 12-week treatment duration
    • C-EDGE TN in treatment-naïve patients; Oral presentation, General Session 2 & Award 1, Abstract #G07, Friday, April 24, 8:30 a.m. – 8:45 a.m. CEST
    • C-EDGE CO-INFXN in patients with HCV/HIV co-infection; E-poster #P0887, Thursday, April 23 at 7:30 a.m. CEST until Saturday, April 25 at 8:00 p.m. CEST
    • C-EDGE TE in treatment-experienced (prior peg-interferon/ribavirin treatment failures); E-poster #P0886, Thursday, April 23 at 7:30 a.m. CEST until Saturday, April 25 at 8:00 p.m. CEST
  • First results from C-SURFER, a Phase 2b/3 clinical trial evaluating grazoprevir/elbasvir (without ribavirin) in treatment-naïve and treatment-experienced patients with HCV genotype 1 infection and advanced chronic kidney disease
    • Late-breaking E-poster #LP02, Thursday, April 23 at 7:30 a.m. CEST until Saturday, April 25 at 8:00 p.m. CEST
  • Results from C-SALVAGE, a Phase 2 clinical trial evaluating grazoprevir/elbasvir (with and without ribavirin) for chronic HCV in genotype 1 infection after failure of direct-acting antiviral (DAA) therapy, including boceprevir, telaprevir, or simeprevir
    • Oral presentation, Viral Hepatitis C Therapy session, Abstract #O001, Thursday, April 23, 4:00 p.m. – 4:15 p.m. CEST
  • Results from C-SWIFT, a Phase 2 clinical trial evaluating shorter treatment durations (4, 6, 8 and 12 weeks) of grazoprevir/elbasvir plus sofosbuvir in treatment-naïve, treatment-experienced/prior treatment failure/null-response, cirrhotic and non-cirrhotic patients with genotype 1 or 3 infection
    • Oral presentation, Viral Hepatitis C Therapy session, Abstract #O006, Thursday, April 23, 5:15 p.m. – 5:30 p.m. CEST
  • Phase 2 efficacy and safety results from the C-SALT clinical trial, evaluating grazoprevir/elbasvir in genotype 1 infected patients with Child-Pugh class B cirrhosis
    • Oral presentation, Viral Hepatitis C Therapy session, Abstract #O008, Thursday, April 23, 5:45 p.m. – 6:00 p.m. CEST
  • Results from C-WORTHy, a Phase 2 clinical trial evaluating treatment with grazoprevir/elbasvir (with or without ribavirin) in genotype 1 and 3 infection, and in a variety of patient sub-populations including treatment-naïve, treatment-experienced, cirrhotic, non-cirrhotic, and HIV/HCV co-infected
    • C-WORTHy Part C in treatment-naïve, non-cirrhotic patients with genotype 1b infection; E-poster #P0769, Thursday, April 23 at 7:30 a.m. CEST until Saturday, April 25 at 8:00 p.m. CEST
    • C-WORTHy Part D in treatment-naïve patients with genotype 3 infection treated with ribavirin; E-poster #P0776, Thursday, April 23 at 7:30 a.m. CEST until Saturday, April 25 at 8:00 p.m. CEST
    • C-WORTHy resistance analysis of virologic failures in hepatitis C genotype 1 infected patients; E-poster #P0891, Thursday, April 23 at 7:30 a.m. CEST until Saturday, April 25 at 8:00 p.m. CEST
  • Results from C-SCAPE, a Phase 2 trial evaluating the efficacy and safety of 12 weeks of grazoprevir/elbasvir (with or without ribavirin) in patients with genotype 2, 4, 5 or 6 infection
    • E-poster #P0771, Thursday, April 23 at 7:30 a.m. CEST until Saturday, April 25 at 8:00 p.m. CEST
  • Results from a Phase 1 study to evaluate the interaction of novel nucleotide inhibitor MK-3682 (formerly IDX21437), with grazoprevir and NS5A inhibitor MK-8408 in healthy subjects
    • E-poster #P0824, Thursday, April 23 at 7:30 a.m. CEST until Saturday, April 25 at 8:00 p.m. CEST

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, 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 healthcare 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. Such statements may include, but are not limited to, Merck’s ability to complete the offering and Merck’s expectations for the use of proceeds from the offering. 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; and timing of the offering.

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).

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