Program Schedule

Daclatasvir and Asunaprevir Plus Peginterferon Alfa-2a and Ribavirin in Patients With HCV Genotype 1 or 4 Infection: Phase 3 HALLMARK-QUAD Results

Session: Poster Abstract Session: Clinical - Clinical Trials
Friday, October 10, 2014
Room: The Pennsylvania Convention Center: IDExpo Hall BC
  • 1014036 4612554-2_IDW_Daclastasvir_Jensen_Poster_PRINT.pdf (326.8 kB)
  • Background: Daclatasvir (DCV) is a potent, pangenotypic NS5A inhibitor. Asunaprevir (ASV) is an NS3 protease inhibitor with activity in HCV genotypes (GT) 1 and 4. DCV plus ASV in combination with peginterferon alfa-2a and ribavirin (DCV+ASV+P/R) has previously demonstrated potent antiviral activity in HCV GT 1-infected null responders. This phase 3 study (HALLMARK-QUAD; AI447029) evaluated DCV+ASV+P/R in patients with chronic HCV GT 1 or 4 infection who were prior null or partial responders to peginterferon/ribavirin.

    Methods: In this open-label study, 354 GT 1 and 44 GT 4-infected patients received 24 weeks of treatment with DCV 60 mg once daily plus ASV 100 mg twice daily in combination with weekly peginterferon alfa-2a 180 µg and weight-based ribavirin twice daily. The primary endpoint was sustained virologic response at posttreatment Week 12 (SVR12).

    Results: The median age of patients was 53 years, 69% were male, 76% were white, and 23% had cirrhosis; 67% of patients were prior null responders and 33% were partial responders. SVR12 was achieved by 93% of GT 1-infected patients and 98% of GT 4-infected patients; one GT 4 patient was not tested for SVR12 but achieved SVR24, yielding an SVR rate of 100% in GT 4-infected patients (Table). Prior P/R response, cirrhosis status, gender, age, race, or IL28B genotype did not influence SVR12. SVR12 rates for GT 1a were 87% (153/176) versus 99% (176/178) for GT 1b. Serious adverse events occurred in 6% of patients; 5% discontinued treatment due to an adverse event. One death occurred at posttreatment week 12 (pneumonia; not considered related to study therapy). Adverse events occurring in ≥20% of patients were fatigue, headache, pruritus, asthenia, influenza-like illness, insomnia and rash. Grade 3/4 laboratory abnormalities included neutropenia (22%), lymphopenia (16%), anemia (6%), thrombocytopenia (4%) and ALT/AST elevations (3%/3%).

    Conclusion: The QUAD regimen of DCV+ASV+P/R demonstrated high SVR12 rates of 93% and 100% in GT 1 or GT 4 prior non-responders. DCV+ASV+P/R was generally well tolerated; no additional safety and tolerability concerns were observed compared to P/R regimens. These results support the investigation of DCV in all-oral combinations in multiple patient populations across genotypes.

    Donald M. Jensen, MD1, Kenneth Sherman, MD2, Christophe Hezode3, Stanislas Pol4,5, Stefan Zeuzem, MD6, Victor De Ledinghen, MD7, Albert Tran8, Magdy Elkhashab9, Ziad H Younes10, Marcelo Kugelmas11, Stefan Mauss, MD12, Gregory T. Everson13, Velimir Luketic14, John Vierling, MD15, Lawrence Serfaty16, Maurizia Brunetto, MD17, Jeong Heo18, David Bernstein19, Fiona Mcphee, PhD20, Delphine Hennicken21, Patricia Mendez22, Eric Hughes, MD, PhD22, Stephanie Noviello23 and HALLMARK-QUAD Study Team, (1)Center for Liver Diseases, University of Chicago Medicine, Chicago, IL, (2)University of Cincinnati Medical Center, Cincinnati, OH, (3)Hopital Henri Mondor, Creteil, France, (4)Hôpital Cochin, Paris, France, (5)Université Paris Descartes, INSERM U1610 and Liver Unit, Hôpital Cochin, Paris, France, (6)Gastroeneterology, Klinikum der Johann-Wolfgang-Goethe-Universität–Med. Klinik I, Frankfurt, Germany, (7)Hopital Haut Leveque, Pessac, France, (8)Hopital De L'Archet 2, Nice Cedex 03 Na, France, (9)Toronto Liver Centre, Toronto, ON, Canada, (10)Gastro One, Germantown, TN, (11)South Denver Gastroenterology, Pc, Englewood, CO, (12)Zentrum für HIV und Hepatogastroenterologie, Düsseldorf, Germany, (13)University of Colorado Denver, Aurora, CO, (14)Mcguire Dvamc, Richmond, VA, (15)Baylor-St. Luke’s Medical Center / St. Luke’s Advanced Liver Therapies, Houston, TX, (16)St Antoine Hospital, Pierre and Marie Curie University, Paris, France, (17)Liver Unit, University Hospital of Pisa, Pisa, Italy, (18)Pusan National University Hospital, Busan, South Korea, (19)North Shore-Long Island Jewish Health System, Manhasset, NY, (20)Bristol-Myers Squibb Research and Development, Wallingford, CT, (21)Bristol-Myers Squibb Research and Development, Braine-l'Alleud, France, (22)Bristol-Myers Squibb Research and Development, Princeton, NJ, (23)Bristol-Myers Squibb, Wallingford, CT


    D. M. Jensen, AbbVie: Grant Investigator, Research grant and Research support
    Boehringer Ingelheim: Grant Investigator, Research grant and Research support
    BMS: Grant Investigator, Research grant and Research support
    Roche/Genentech: Grant Investigator, Research grant and Research support
    Pharmasset/Gilead: Grant Investigator, Research grant and Research support
    Tibotec/Janssen: Grant Investigator, Research grant and Research support

    K. Sherman, Bristol-Myers Squibb: Investigator, Research grant

    C. Hezode, None

    S. Pol, Bristol-Myers Squibb: Board Member and Investigator, Research grant and Speaker honorarium

    S. Zeuzem, Bristol-Myers Squibb: Consultant, Consulting fee and Speaker honorarium

    V. De Ledinghen, AbbVie: Scientific Advisor, Consulting fee
    BMS: Scientific Advisor, Consulting fee
    Gilead: Scientific Advisor, Consulting fee
    Merck: Scientific Advisor, Consulting fee
    Janssen: Scientific Advisor, Consulting fee
    Echosens: Scientific Advisor, Consulting fee

    A. Tran, Britsol-Myers Squibb: Investigator, Research grant and Research support

    M. Elkhashab, Bristol-Myers Squibb: Investigator, Research grant

    Z. H. Younes, Bristol-Myers Squibb: Investigator, Research grant

    M. Kugelmas, None

    S. Mauss, Britsol-Myers Squibb: Scientific Advisor, Speaker honorarium

    G. T. Everson, Bristol-Myers Squibb: Consultant and Investigator, Consulting fee, Research grant and Research support

    V. Luketic, None

    J. Vierling, Abbvie, Biotest, BMS, Gilead, Janssen, Vertex, Merck, Genentech, Genfit, Hyperion, Intercept, Ocera, Sundise: Research Contractor, Research support
    Abbvie, Boerhinger-Ingelheim, BMS, Gilead, Janssen, Merck, Hyperion, Intercept, Sundise: Scientific Advisor, Consulting fee

    L. Serfaty, None

    M. Brunetto, AbbVie, BMS, Gilead, Janssen, MSD, Roche, Novartis: Speaker's Bureau, Speaker honorarium

    J. Heo, None

    D. Bernstein, Bristol-Myers Squibb: Investigator, Research grant

    F. Mcphee, BMS: Employee, Salary

    D. Hennicken, Bristol-Myers Squibb: Employee, Salary

    P. Mendez, Bristol-Myers Squibb: Employee, Salary

    E. Hughes, BMS: Employee, Salary

    S. Noviello, Bristol-Myers Squibb: Employee and Shareholder, Salary

    Findings in the abstracts are embargoed until 12:01 a.m. EDT, Oct. 8th with the exception of research findings presented at the IDWeek press conferences.

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