430. Analysis of HCV Genotype 2 and 3 Variants in Patients Treated with Combination Therapy of Next Generation HCV Direct-Acting Antiviral Agents ABT-493 and ABT-530
Session: Poster Abstract Session: Hepatitis C
Thursday, October 27, 2016
Room: Poster Hall
Background: ABT-493 (NS3/4A protease inhibitor identified by AbbVie and Enanta) and ABT-530 (NS5A inhibitor) are next generation HCV direct-acting antiviral agents. Co-administration of ABT-493 and ABT-530 ± ribavirin for 12 weeks achieved high sustained virologic response (SVR) in patients with HCV GT1, GT2, or GT3 infection in the dose-ranging studies of SURVEYOR-I and -II. In this report, we characterize GT2 and GT3 variants detected in samples from SURVEYOR-II.

Methods: Population sequencing was performed on NS3 and NS5A genes from all baseline (BL) samples, and the first available sample after virologic failure (VF) with HCV RNA ≥1000 IU/mL. Sequences were examined for variants at positions where resistance to drugs in the protease or NS5A inhibitor class is known: NS3 positions 36, 56, 80, 155, 156, 166 (GT3 only), and 168, and NS5A positions 24, 28, 29, 30, 31, 32, 58, 92, and 93.

Results: For BL samples from GT2-infected patients (n= 74), 36 had M31 in NS5A, a common polymorphism that confers resistance to a number of NS5A inhibitors but not to ABT-530. In addition, 6 patients had other BL NS5A variants, 5 patients had a BL NS3 variant, and 2 patients had variants in both targets at BL. Irrespective of the presence of BL variants, all GT2-infected patients, except 1 lost to follow-up (LTFU), achieved SVR12. For GT3-infected patients (n= 121), 17 had NS3 variants, 19 had NS5A variants, and 5 had variants in both targets at BL. Seven GT3-infected patients experienced VF; only 1of these VFs (a relapse) occurred in a patient enrolled in an arm receiving the 300mg/120mg ABT-493/ABT-530 dose combination (n=30). For this patient, no NS3 variants and 1 NS5A variant (A30K) were detected at BL; a double NS3 variant (Y56H+Q168R) and a double NS5A variant (A30K+Y93H) were detected at VF. The other 6 VF patients were treated with lower combination doses; variant analysis will be presented.

Conclusion: All GT2-infected patients, except 1 LTFU, achieved SVR12 regardless of presence or absence of BL NS3 or NS5A variants. For GT3-infected patients, VF occurred in only 1 patient receiving 300mg/120mg ABT-493/ABT-530, the dose chosen for further studies. Evaluation of more GT3-infected patients receiving this dose to fully assess the impact of BL variants on treatment outcome is ongoing.

Teresa Ng, PhD, Tami Pilot-Matias, PhD, Rakesh Tripathi, MS, Gretja Schnell, PhD, Thomas Reisch, MS, Jill Beyer, BS, Tanya Dekhtyar, MS, Stanley Wang, MD, PhD, Federico Mensa, MD, Jens Kort, MD, PhD and Christine Collins, PharmD, AbbVie Inc., North Chicago, IL

Disclosures:

T. Ng, AbbVie: Employee and Shareholder , Salary

T. Pilot-Matias, AbbVie: Employee and Shareholder , Salary

R. Tripathi, AbbVie: Employee and Shareholder , Salary

G. Schnell, AbbVie: Employee and Shareholder , Salary

T. Reisch, AbbVie: Employee and Shareholder , Salary

J. Beyer, AbbVie: Employee and Shareholder , Salary

T. Dekhtyar, AbbVie: Employee and Shareholder , Salary

S. Wang, AbbVie: Employee and Shareholder , Salary

F. Mensa, AbbVie: Employee and Shareholder , Salary

J. Kort, AbbVie: Employee and Shareholder , Salary

C. Collins, AbbVie: Employee and Shareholder , Salary

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