Interim Analysis of an Interferon (IFN)- And Ribavirin (RBV)-Free Regimen of Daclatasvir (DCV), Asunaprevir (ASV), and BMS-791325 In Treatment-Naive, Hepatitis C Virus Genotype 1-Infected Patients

Infectious Disease Week (IDWeek)
October 2-6, 2013
San Francisco, Ca

1828. Interim Analysis of an Interferon (IFN)- And Ribavirin (RBV)-Free Regimen of Daclatasvir (DCV), Asunaprevir (ASV), and BMS-791325 In Treatment-Naive, Hepatitis C Virus Genotype 1-Infected Patients

Session: Oral Abstract Session: Hepatitis C

Saturday, October 5, 2013: 2:45 PM

Room: The Moscone Center: 250-262

Background: The IFN- and RBV-free regimen of DCV (NS5A inhibitor), ASV (protease inhibitor) and BMS-791325 (non-nucleoside NS5B inhibitor, 75mg BID) achieved sustained virologic response (SVR4, SVR12) >90% in treatment-naïve, hepatitis C virus (HCV) genotype (GT) 1 patients. We evaluated this regimen using two BMS-791325 doses (75 vs 150 mg BID).

Methods: HCV GT1, treatment-naïve, non-cirrhotic patients (N=32) were randomized 1:1 to DCV 60mg QD, ASV 200mg BID, and BMS-791325 75mg BID for 24 (Group 1) or 12 (Group 2) weeks. Subsequently, 34 additional patients were randomized to DCV, ASV, and BMS-791325 150mg BID for 24 (Group 3) or 12 (Group 4) weeks. The primary end point was HCV RNA <25 IU/mL at 12 weeks post-treatment (SVR12). Interim results are presented.

Results: Patients were mainly GT1a (74%), white (79%), and IL28Bnon-CC (70%). 64/66 patients had HCV RNA <25 IU/mL by Week 4 (Table). There was no difference in virologic response between 12 and 24 weeks of treatment. Overall, patients achieved SVR4 92% (46/50), SVR12 94% (30/32), and SVR24 94% (15/16). No patient discontinued for adverse events (AEs) related to DCV+ASV+BMS-791325. Most common AEs (≥10% total) were headache, asthenia, and gastrointestinal. Two serious AEs were reported, both unrelated to DCV+ASV+BMS-791325. No hepatotoxicity or Grade 3/4 elevations of ALT/AST or bilirubin were reported.

Conclusion: DCV+ASV+BMS-791325 achieved high rates of SVR4, SVR12, and SVR24 in treatment-naive GT1 patients, characterized by GT1a and IL28Bnon-CC. This regimen was well tolerated with no apparent safety signals. Expansion of the current study is underway to better define the efficacy and safety of this regimen.

Virologic Response During and After Treatment

BMS-791325 Dose		75 mg				150 mg
Duration		24 weeks		12 weeks		24 weeks		12 weeks
Group		1 (N=16)		2 (N=16)		3 (N=16)		4 (N=18)
HCV RNA <25IU/mL, n(%)
Week 4		16(100)		16(100)		16(100)		16(89)a
EOT/Last on-treatment		15(94)b		16(100)		-		17(94)c
SVR4		15(94)b		15(94)d		-		16(89)c,e
SVR12		15(94)b		15(94)d		-		-
SVR24		-		15(94)f		-		-
Virologic breakthrough, n(%)		0		0		1(7)		1(6)
Relapse, n(%)		0		0		-		1(6)
aOne patient with isolated HCV RNA of 43 IU/mL, one patient missing; b Patient withdrew consent; cOne viral breakthrough; dOne missing; eOne relapse; fA second patient missing.

Gregory T. Everson¹, Karen D. Sims², Maribel Rodriguez-Torres, MD³, Christophe Hézode⁴, Eric Lawitz⁵, Marc Bourlière⁶, Veronique Loustaud-Ratti⁷, Vinod Rustgi⁸, Howard Schwartz⁹, Harvey Tatum¹⁰, Patrick Marcellin¹¹, Stanislas Pol¹², Paul J. Thuluvath¹³, Timothy Eley, PhD², Xiaodong Wang², Shu-Pang Huang¹⁴, Fiona Mcphee¹⁵, Megan Wind-Rotolo¹⁴, Ellen Chung², Claudio Pasquinelli², Dennis M. Grasela² and David F. Gardiner², (1)University of Colorado Denver, Aurora, CO, (2)Bristol-Myers Squibb, Hopewell, NJ, (3)Gastroenterology, Fundacion de Investigacion, Rio Piedras, PR, (4)CHU Henri Mondor, Service d’Hépato-Gastroentérologie, Créteil, France, (5)Alamo Medical Research, San Antonio, TX, (6)Hôpital Saint Joseph, Service d’Hépato-Gastroentérologie, Marseille, France, (7)University Hospital of Limoges, Limoges, France, (8)Metropolitan Research, Arlington, VA, (9)Miami Research Associates, South Miami, FL, (10)Options Health Research, Tulsa, OK, (11)Hôpital Beaujon, Clichy, France, (12)Université Paris Descartes, INSERM U1610 and Liver Unit, Hôpital Cochin, Paris, France, (13)Mercy Medical Center, Baltimore, MD, (14)Bristol-Myers Squibb, Princeton, NJ, (15)Bristol-Myers Squibb, Wallingford, CT

Disclosures:

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

K. D. Sims, Bristol-Myers Squibb: Employee, Salary

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

C. Hézode, Bristol-Myers Squibb: Investigator, Research support

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

M. Bourlière, Bristol-Myers Squibb: Investigator, Research support

V. Loustaud-Ratti, Bristol-Myers Squibb: Investigator, Research support

V. Rustgi, Bristol-Myers Squibb: Investigator, Research support

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

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

P. Marcellin, Bristol-Myers Squibb: Investigator, Research support

S. Pol, Bristol-Myers Squibb: Investigator, Research support

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

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

X. Wang, Bristol-Myers Squibb: Employee, Salary

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

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

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

E. Chung, Bristol-Myers Squibb: Employee, Salary

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

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

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

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