EASL 2014 - CARE Liver Disease Faculty - LBA O166: Phase 3 Study Results

All-Oral Dual Therapy With Daclatasvir And Asunaprevir In Patients With HCV Genotype 1b Infection

M. Manns,1 S. Pol,2 I. Jacobson,3 P. Marcellin,4 S. Gordon,5 C.-Y. Peng,6, T.-T. Chang,7, G. Everson,8 J. Heo,9 G. Gerken,10 B. Yoffe,11 W.J. Towner,12 M. Bourliere,13 S. Metivier,14 C.-J. Chu,15 W. Sievert,16 J.-P. Bronowicki,17 D. Thabut,18 Y.-J. Lee,19 J.-H. Kao,20 F. McPhee,21 J. Kopit,21 P. Mendez,22 M. Linaberry,22 E. Hughes,22 S. Noviello,22 HALLMARK DUAL Study Team

Background and Aims: Daclatasvir plus asunaprevir dual oral therapy (DCV+ASV) has demonstrated potent antiviral activity in HCV genotype 1b infection. This phase 3 study (AI447028) evaluated DCV+ASV in a broad range of patients, including those with cirrhosis.

Results: Overall, patients were 49% male, 68% white, and 71% IL28B non-CC; 30% had cirrhosis. SVR12 rates among DCV+ASV-treated patients were 90%, 82%, and 82% in the naive, null/partial, and ineligible/intolerant groups (Table 1). No differences in SVR12 rates were observed based on age, gender, race, or IL28B genotype; SVR12 rates were similar across all groups in non-cirrhotic (85%; n=437) and cirrhotic (84%; n=206) patients. Serious AEs occurred in 6% and AEs leading to discontinuation (reversible elevated ALT/AST most common) in 2%, with no deaths. Grade 3/4 laboratory abnormalities were uncommon, including low incidences of ALT elevations (first 12 weeks) with DCV+ASV or placebo in naive patients (2% for both).

Conclusions: DCV+ASV provided high SVR12 rates of 90% (treatment-naïve) and >80% (null/partial and ineligible/intolerant), including in cirrhotics, and was generally well tolerated in patients with HCV genotype 1b infections.

This study of G1b patients is not very generalizable to Canada, where only 1/3rd of our Genotype 1 population is 1b (the rest are 1a). Cirrhotic patients included in this study are well compensated. In the G1b population this regimen of an NS5A inhibitor and an NS3 protease inhibitor performs reasonably well although it is unlikely that it will be used as is given comparable SVR rates are seen with IFN-based regimens and better rates are seen with other all-oral regimens. Daclatasvir is a good NS5A inhibitor, and if this regimen is approved then it would be reasonable to consider combining that drug alone with other approved regimens to maximize SVR. Overall, it is unlikely that this combination of agents will be used in clinical practice together without anything else.
— CARE Liver Disease Faculty Perspectives

1Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany, 2Hôpital Cochin, Paris, France, 3Weill Cornell Medical College, New York, NY, United States,4Hopital Beaujon, Clichy, France, 5Henry Ford Health Systems, Detroit, MI, United States, 6School of Medicine, China Medical University, Taichung, 7National Chen Kung University Hospital, Tainan, Taiwan,8University Of Colorado Denver, Aurora, CO, United States, 9Pusan National University Hospital, Busan, Korea, Republic of, 10University of Duisburg-Essen, Essen, Germany, 11VAMC, Baylor College of Medicine, Houston, TX, 12Kaiser Permanente, Los Angeles, CA, United States, 13Hôpital Saint Joseph, Marseille, 14CHU Purpan, Toulouse, France, 15Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan, 16Monash Health and Monash University, Melbourne, VIC, Australia, 17INSERM Unité 954, Centre Hospitalier Universitaire de Nancy and Université de Lorraine, Vandoeuvre-lés-Nancy, 18Hôpital Pitié-Salpêtrière, Paris, France, 19Inje University Busan Paik Hospital, Busan, Korea, Republic of, 20National Taiwan University Hospital, Taipei, Taiwan, 21Bristol-Myers Squibb Research and Development, Wallingford, CT, 22Bristol-Myers Squibb Research and Development, Princeton, NJ, United States