1357. Sustained Virologic Response With Daclatasvir Plus Sofosbuvir ± Ribavirin (RBV) In Chronic HCV Genotype (GT) 1-Infected Patients Who Previously Failed Telaprevir (TVR) Or Boceprevir (BOC)
Session: Poster Abstract Session: Clinical Trials
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C

Background:  Daclatasvir (DCV) plus sofosbuvir (SOF) ±RBV achieved high rates of sustained virologic response in HCV GT1-3-infected previously untreated patients (arms A-H). Additional arms (I, J) evaluated the efficacy of DCV+SOF ±RBV in patients who failed TVR or BOC.

Methods:  A total of 41 GT1 non-cirrhotic patients with previous breakthrough (n=15), relapse (n=13), or nonresponse (n=14) to pegIFN/RBV+TVR (n=33) or BOC (n=9) (1 patient received both) were randomized 1:1 to DCV+SOF with or without RBV for 24 weeks. Patients who discontinued TVR or BOC due to adverse events were excluded. DCV and SOF were dosed orally at 60mg QD and 400mg QD, respectively. RBV was dosed BID at 1000-1200 mg/d. The primary end point was HCV RNA<25 IU/mL at 12 weeks post-treatment (SVR12).

Results: Most patients had HCV GT1a (83%), were IL28B non-CC (98%), and had estimated METAVIR stage ≥F2 (83%). Mean HCV RNA was ≥6 log IU/mL. HCV RNA <25 IU/mL was achieved in 40/41 patients by week 4 and in all patients by end of treatment. None had breakthrough or relapse and all patients with available data (40/41) achieved SVR12 (Table). The most common adverse events (>30% total) were fatigue and headache. There were no grade 3-4 hematologic or hepatic laboratory abnormalities. 

Conclusion : The all-oral, once-daily combination of DCV+SOF with or without RBV for 24 weeks achieved SVR12 in 98% of non-cirrhotic GT1 prior TVR/BOC treatment failures. These data provide proof-of-concept that the combination of two potent direct-acting antivirals with different viral targets is effective in patients who failed pegIFN/RBV + a protease inhibitor.

HCV RNA < 25 IU/mL, mITT

 I

DCV + SOF

 x 24 weeks

 (n = 21)

J

DCV + SOF  + RBV

x 24 weeks

 (n = 20)

Week 4

21 (100)

19 (95)a

End Of Treatment  (Week 24)

21 (100)

20 (100)

SVR4

21 (100)

20 (100)

SVR12

21 (100)

19 (95)b

a 1 missing; b 1 missing—patient had HCV RNA undetectable at post-treatment  week4 and post-treatment week 24 (preliminary)

Mark Sulkowski, MD1, David Gardiner2, Maribel Rodriguez-Torres, MD3, K. Rajender Reddy, MD4, Tarek Hassanein, MD5, Ira Jacobson, MD6, Eric Lawitz7, Anna S.F. Lok, MD, FRCP8, Federico Hinestrosa9, Paul J. Thuluvath10, Howard Schwartz11, David Nelson12, Gregory T. Everson13, Timothy Eley, PhD14, Megan Wind-Rotolo15, Shu-Pang Huang15, Min Gao16, Fiona Mcphee16, Dennis Hernandez16, Diane Sherman2, Robert Hindes17, William Symonds, PharmD18, Claudio Pasquinelli14, Dennis Grasela, PharmD, PhD19 and AI444040 Study Group, (1)John Hopkins University School of Medicine, Baltimore, MD, (2)Bristol-Myers Squibb, Pennington, NJ, (3)Gastroenterology, Fundacion de Investigacion, Rio Piedras, PR, (4)Univ. of Pennsylvania, Philadelphia, PA, (5)230 Prospect Place, Suite 220, Southern California Liver Centers, Coronado, CA, (6)Weill Medical College of Cornell University, New York, NY, (7)Texas Liver Insititute, University of Texas Health Science Center, San Antonio, TX, (8)Internal Medicine, University of Michigan, Ann Arbor, MI, (9)Orlando Immunology Center, Orlando, FL, (10)Mercy Medical Center, Baltimore, MD, (11)Miami Research Associates, South Miami, FL, (12)University of Florida, Gainesville, FL, (13)University of Colorado Denver, Aurora, CO, (14)Bristol-Myers Squibb, Hopewell, NJ, (15)Bristol-Myers Squibb, Princeton, NJ, (16)Bristol-Myers Squibb, Wallingford, CT, (17)Consultant, Foster City, CA, (18)Gilead Sciences, Foster City, CA, (19)Bristol Myers-Squibb, Hopewell, NJ

Disclosures:

M. Sulkowski, AbbVie: Investigator and Scientific Advisor, Consulting fee and Research grant
BIPI: Investigator, Research Contractor and Scientific Advisor, Consulting fee and Research grant
BMS: Investigator and Scientific Advisor, Consulting fee and Research grant
Gilead : Investigator and Scientific Advisor, Consulting fee and Research grant
Janssen: Consultant, Investigator and Scientific Advisor, Consulting fee and Research grant
Merck : Investigator and Scientific Advisor, Research grant
Pfizer: Steering Committe, Consulting fee
Vertex: Investigator and Scientific Advisor, Consulting fee and Research grant

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

M. Rodriguez-Torres, Bristol-Myers Squibb: Investigator, Research support

K. R. Reddy, Bristol-Myers Squibb: Investigator, Research support

T. Hassanein, Bristol-Myers Squibb: Investigator, Research support

I. Jacobson, Bristol-Myers Squibb: Investigator, Research support

E. Lawitz, Bristol-Myers Squibb: Investigator, Research support

A. S. F. Lok, Bristol-Myers Squibb: Investigator, Research support

F. Hinestrosa, Bristol-Myers Squibb: Investigator, Research support

P. J. Thuluvath, Bristol-Myers Squibb: Investigator, Research support

H. Schwartz, Bristol-Myers Squibb: Investigator, Research support

D. Nelson, Bristol-Myers Squibb: Investigator, Research support

G. T. Everson, Bristol-Myers Squibb: Investigator, Research support

T. Eley, Bristol-Myers Squibb: Employee, Salary

M. Wind-Rotolo, Bristol-Myers Squibb: Employee, Salary

S. P. Huang, Shu-Pang Huang: Employee, Salary

M. Gao, Bristol-Myers Squibb: Employee, Salary

F. Mcphee, Bristol-Myers Squibb: Employee, Salary

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

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

R. Hindes, Bristol-Myers Squibb: Research Contractor, Research support

W. Symonds, Gilead Sciences: Employee, Salary

C. Pasquinelli, Bristol-Myers Squibb: Employee, Salary

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

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