Author(s): Jensen D, Sherman KE, Hézode C, Pol S, Zeuzem S, et al.
Background & aims: Improved therapies for peginterferon/ribavirin null or partial responders are needed. This study evaluated daclatasvir (NS5A inhibitor) and asunaprevir (NS3 protease inhibitor) plus peginterferon alfa-2a and ribavirin in this patient population.
Methods: This open-label, phase 3 study (HALLMARK-QUAD; NCT01573351) treated patients with chronic hepatitis C virus (HCV) genotype 1 (n=354) or 4 (n=44) infection who had a prior null or partial response to peginterferon/ribavirin. Patients received daclatasvir 60 mg once-daily plus asunaprevir 100mg twice-daily, with weekly peginterferon alfa-2a and weight-based ribavirin for 24 weeks. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12) among genotype 1-infected patients.
Results: Daclatasvir plus asunaprevir and peginterferon/ribavirin demonstrated SVR12 rates of 93% (95% CI 90-96) in prior non-responders infected with HCV genotype 1. SVR12 rates among genotype 4-infected patients were 98% (95% CI 93-100); one patient had a missing post-treatment week-12 HCV-RNA measurement, but achieved an SVR at post-treatment week 24, yielding a 100% SVR rate in genotype 4 patients. Prior peginterferon/ribavirin response, sex, age, IL28B genotype, or cirrhosis status did not influence SVR12 rates. Serious adverse events occurred in 6% of patients; 5% discontinued treatment due to an adverse event. Grade 3/4 laboratory abnormalities included neutropenia (22%), lymphopenia (16%), anemia (6%), thrombocytopenia (4%), and ALT/AST elevations (3% each).
Conclusions: Daclatasvir plus asunaprevir and peginterferon/ribavirin demonstrated high rates of SVR12 in genotype 1- or 4-infected prior null or partial responders. The combination was well tolerated and no additional safety and tolerability concerns were observed compared with peginterferon/ribavirin regimens.
Referred From: https://www.ncbi.nlm.nih.gov/pubmed/25703086
Author(s): Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, et al.
Author(s): Global Burden Of Hepatitis C Working Group
Author(s): Pawlotsky JM, Chevaliez S, McHutchison JG
Author(s): Thompson A, Patel K, Tillman H, McHutchison JG
Author(s): Messina JP, Humphreys I, Flaxman A, Brown A, Cooke GS, et al.
Author(s): Al Traif I, Al Balwi MA, Abdulkarim I, Handoo FA, Alqhamdi HS, et al.
Author(s): Ray SC, Arthur RR, Carella A, Bukh J, Thomas DL
Author(s): Benhamou Y, Moussalli J, Ratziu V, Lebray P, De Backer K, et al.
Author(s): Omland LH, Osler M, Jepsen P, Krarup H, Weis N, et al.
Author(s): Reddy KR, Wright TL, Pockros PJ, Shiffman M, Everson G, et al.
Author(s): Hasan F, Asker H, Al-Khaldi J, Siddique I, Al-Ajmi M, et al.
Author(s): Alfaleh FZ, Hadad Q, Khuroo MS, Aljumah A, Algamedi A, et al.
Author(s): Derbala M, Amer A, Bener A, Lopez AC, Omar M, et al.
Author(s): El Makhzangy H, Esmat G, Said M, Elraziky M, Shouman S, et al.
Author(s): Kamal SM, Ahmed A, Mahmoud S, Nabegh L, El Gohary I, et al.
Author(s): Abdo AA, Al-Ahdal MN, Khalid SS, Helmy A, Sanai FM, et al.
Author(s): Kamal SM, E Kamary SS, Shardell MD, Hashem M, Ahmed IN, et al.
Author(s): MartÃn-Carbonero L, Puoti M, GarcÃa-Samaniego J, De Luca A, Losada E, et al.
Author(s): Issa H
Author(s): Kowdley KV, Lawitz E, Crespo I, Hassanein T, Davis MN, et al.
Author(s): Lawitz E, Mangia A Wyles D, Rodriguez-Torres M, Hassanein T, et al.
Author(s): Wehmeyer MH, Jordan S, Lüth S, Hartl J, Stoehr A, et al.
Author(s): Steinebrunner N, Sprinzl MF, Zimmermann T, Wörns MA, Zimmerer T, et al.
Author(s): Moreno C, Hezode C, Marcellin P, Bourgeois S, Francque S, et al.
Author(s): Hézode C, Hirschfield GM, Ghesquiere W, Sievert W, Rodriguez-Torres M, et al.
Author(s): Hézode C, Alric L, Brown A, Hassanein T, Rizzetto M, et al.
Author(s): Zoulim F, Liang TJ, Gerbes AL Aghemo A4, Deuffic-Burban S5, et al.
Author(s): Petersen T, Townsend K, Gordon LA, Sidharthan S, et al.
Author(s): Molina JM, Orkin C, Iser DM, Zamora FX, Nelson M, et al.
Author(s): Ruane PJ, Ain D, Stryker R, Meshrekey R, Soliman M, et al.
Author(s): Doss W, Shiha G, Hassany M, Soliman R, Fouad R, et al.
Author(s): Lawitz E, Sulkowski MS, Ghalib R, Rodriguez-Torres M, Younossi ZM, et al.
Author(s): Sulkowski MS, Gardiner DF, Rodriguez-Torres M, Reddy KR, Hassanein T, et al.
Author(s): Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, et al.
Author(s): Kohli A, Kapoor R2, Sims Z3, Nelson A4, Sidharthan S3, et al.
Author(s): Charlton M, Everson GT, Flamm SL, Kumar P, Landis C, et al.
Author(s): Hézode C, Asselah T, Reddy KR, Hassanein T, Berenguer M, et al.
Author(s): Zeuzem S, Ghalib R, Reddy KR, Pockros PJ, Ari ZB, et al.