Program Schedule

819
Daclatasvir in Combination with Peginterferon Alfa-2a and Ribavirin for Treatment-Naive Patients with HCV Genotype 4 Infection: Phase 3 COMMAND-4 Results

Session: Poster Abstract Session: Clinical - Clinical Trials
Friday, October 10, 2014
Room: The Pennsylvania Convention Center: IDExpo Hall BC
Posters
  • 1014036 4612554-8_IDW_Daclastasvir_Hezode_Poster_PRINT_r1 (1).pdf (809.2 kB)
  • Background: Options are limited concerning treatment of HCV genotype (GT) 4 infection, therefore, new regimens containing direct-acting antiviral agents are being evaluated. In phase 2b studies, daclatasvir (DCV), a pan-genotypic HCV NS5A inhibitor, combined with peginterferon-alfa/ribavirin (P/R) demonstrated greater efficacy in GTs 1-4 than P/R alone, including a 100% sustained virologic response (SVR) rate in GT 4. This phase 3 study (COMMAND-4; AI444042) evaluated the efficacy and safety of DCV plus P/R in treatment-naive patients with GT 4 infection.

    Methods: Patients were randomized (2:1; blinded) and treated with DCV 60 mg (n=82) or placebo (n=42) once daily with peginterferon alfa 180 µg once weekly and ribavirin 1000-1200 mg/day (weight-based) twice daily. DCV-treated patients with undetectable HCV RNA at weeks 4 and 12 (eRVR) received 24 weeks of DCV + P/R; those without an eRVR received an additional 24 weeks of P/R. All patients in the placebo arm received 48 weeks of P/R. The primary endpoint was SVR at posttreatment Week 12 (SVR12).

    Results: Patients were 73% male, 77% white and 19% black; 75% were IL28B non-CC and 11% had cirrhosis. There was a diverse representation of GT 4 subtypes, with GT 4A, 4C, or 4D being the most common (57%). SVR12 rates (HCV RNA <LLOQ at posttreatment Week 12 or later) were 82% (67/82) with DCV + P/R vs 43% (18/42) with P/R alone (P<0.0001). In DCV recipients, there were no notable effects on SVR12 rates according to baseline factors (IL28B genotype, age, race, gender, cirrhosis status, baseline viral load) known to impact response to P/R. 9.8% of DCV + P/R recipients experienced serious AEs and 3.7% discontinued due to an AE (neutropenia, uveitis, cerebrovascular accident); in patients receiving P/R alone, 4.8% had serious AEs and 7.1% discontinued due to an AE (Grave's disease, abdominal pain, hypersensitivity). There were no deaths.

    Conclusion: In treatment-naive patients with GT 4 infection, DCV + P/R achieved higher SVR12 rates than P/R alone, with the majority of DCV recipients requiring only 24 weeks of therapy. The safety and tolerability profile of DCV + P/R was comparable to that of P/R alone. These data support DCV-based regimens for GT 4 infection, including all-oral combinations with other direct-acting antivirals.

    Christophe Hézode, MD, PhD1, Laurent Alric, MD, PhD2, Ashley Brown, MD3, Tarek Hassanein, MD4, Mario Rizzetto, MD5, Maria Buti, MD6, Marc Bourliere, MD7, Dominique Thabut, MD8, Esther Molina, MD9, Fiona Mcphee, PhD10, Zhaohui Liu, PhD11, Philip Yin, MD, PhD10, Eric Hughes, MD, PhD12, Michelle Treitel, PhD12 and COMMAND 4 study team, (1)Hôpital Henri Mondor, Créteil, France, (2)CHU Purpan, Toulouse, France, (3)Imperial College Healthcare NHS Trust, London, United Kingdom, (4)Southern California Liver Centers and Southern California Research Center, Coronado, CA, (5)University of Torino, Torino, Italy, (6)Hospital Valle Hebron and Ciberehd del Institut Carlos III, Barcelona, Spain, (7)Hôpital Saint-Joseph, Marseille, France, (8)Groupe Hospitalier Pitié-Salpêtrière, Paris, France, (9)Comp. H. U. De Santiago, A Coruna, Spain, (10)Bristol-Myers Squibb Research and Development, Wallingford, CT, (11)Bristol-Myers Squibb Research and Development, Hopewell, NJ, (12)Bristol-Myers Squibb Research and Development, Princeton, NJ

    Disclosures:

    C. Hézode, BMS: Investigator, Research grant

    L. Alric, BMS: Investigator, Research grant

    A. Brown, BMS: Investigator, Research grant

    T. Hassanein, AbbVie: Grant Investigator and Scientific Advisor, Consulting fee and Research grant
    Boehringer Ingelheim: Grant Investigator, Research grant
    BMS: Grant Investigator, Scientific Advisor and Speaker's Bureau, Consulting fee, Research grant and Speaker honorarium
    Eisai: Grant Investigator, Research grant
    Gilead: Grant Investigator and Speaker's Bureau, Research grant and Speaker honorarium
    Janssen: Grant Investigator, Research grant
    Idenix: Grant Investigator, Research grant
    Ikaria: Grant Investigator, Research grant
    Mochida: Grant Investigator, Research grant
    Roche: Grant Investigator, Research grant
    Ocera: Grant Investigator, Research grant
    Taigen: Grant Investigator, Research grant
    Salix: Grant Investigator and Speaker's Bureau, Research grant and Speaker honorarium
    Sundise: Grant Investigator, Research grant
    Baxter: Speaker's Bureau, Speaker honorarium
    Takeda: Grant Investigator, Research grant
    Vertex: Grant Investigator, Research grant

    M. Rizzetto, BMS: Investigator, Research grant

    M. Buti, BMS: Investigator, Research grant

    M. Bourliere, BMS: Investigator, Research grant

    D. Thabut, BMS: Investigator, Research grant

    E. Molina, BMS: Investigator, Research grant

    F. Mcphee, BMS: Employee, Salary

    Z. Liu, BMS: Employee, Salary

    P. Yin, BMS: Employee, Salary

    E. Hughes, BMS: Employee, Salary

    M. Treitel, BMS: Employee, 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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