July 2, 2013

IAS 2013: 7th IAS Conference on HIV
Pathogenesis Treatment and Prevention
June 30 - July 3 2013
Kuala Lumpur, Malaysia

TUAB0103 - Oral Abstract Session
Safety of ribavirin-containing regimens of ABT-450/r, ABT-333 and ABT-267 for the treatment of HCV genotype 1 infection and efficacy in subjects with ribavirin dose reductions
Presented by Barry Bernstein (United States).
D. Cohen, W. Xie, L. Larsen, C. Marincic, M. Knauss-Townsend, A. Khatri, T. Podsadecki, B. Bernstein
AbbVie Inc., North Chicago, United States

Background: Sustained virologic response (SVR12) rates of 93-99% have been reported for HCV genotype 1 (GT1)-infected subjects treated with a peginterferon (pegIFN)-free, 3 direct-acting antiviral (DAA) regimen of ABT-450/r (HCV protease inhibitor dosed with ritonavir 100 mg, identified as a lead compound by AbbVie and Enanta), ABT-267 (NS5A inhibitor), and ABT-333 (non-nucleoside NS5B inhibitor) plus ribavirin (RBV). When used with pegIFN, RBV has been associated with adverse events (AEs) including anemia, necessitating frequent RBV dose reductions. Rate of RBV dose reduction was approximately 30% in HCV GT1-infected subjects treated with pegIFN/RBV in the IDEAL study. We examined the safety of a RBV-containing, 3-DAA, pegIFN-free regimen and the impact of RBV dose reduction on treatment response.

Methods: 571 non-cirrhotic treatment-naïve and previous pegIFN/RBV null responding patients with chronic HCV GT1 infection were enrolled in Study M11-652. We analyzed the subset receiving ABT-450/r (100/100-150/100 mg QD), ABT-267 (25 mg QD), and ABT-333 (400 mg BID) plus weight-based RBV for 12 or 24 weeks. SVR12 rates (percent of patients with HCV RNA < 25 IU/mL at post-treatment week 12) were analyzed (ITT).

Results: 247 patients (159 treatment-naïve and 88 previous null responders) received a 12- or 24-week regimen of 3 DAAs + RBV. Four patients (1.6%) discontinued due to study drug-related AEs, and 1 patient (0.4%) had a serious AE (arthralgia) considered possibly related to study drug. Hemoglobin values < 10 g/dL and < 8.5 g/dL occurred in 16 (6.5%) and 1 (0.4%) subjects during treatment, respectively. RBV dose was reduced in 27 subjects (10.9%) due to toxicity. Sixteen of the 27 reductions were due to anemia AEs. Other AEs, including diarrhea, fatigue, increased blood creatinine, and dizziness, led to RBV dose reductions less frequently. The table shows SVR12 rates.

  Treatment-naive subjects Previous null responders
RBV dose reduced 21/21 (100) 6/6 (100)
RBV dose not reduced 129/138 (93.5) 76/82 (92.7)
[ITT SVR12 Rates by RBV Dose Reduction Status]

Conclusions: RBV dose reductions were required less frequently with this pegIFN-free regimen than in previously reported studies of subjects receiving pegIFN-containing regimens. High SVR12 rates (100%) were achieved among subjects requiring RBV dose reduction.



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