title: A phase 3, open-label study of daclatasvir plus asunaprevir in Asian patients with chronic hepatitis C virus genotype 1b infection who are ineligible for or intolerant to interferon alfa therapies with or without ribavirin.
abstract: OBJECTIVE
  Daclatasvir plus asunaprevir has demonstrated efficacy and safety in patients with chronic hepatitis C virus genotype 1b infection. This study focused on evaluating daclatasvir plus asunaprevir in interferon (±ribavirin)-ineligible or -intolerant Asian patients with genotype 1b infection from mainland China, Korea, and Taiwan.
  
  
  METHODS
  Interferon (±ribavirin)-ineligible and -intolerant patients with genotype 1b infection received daclatasvir 60 mg tablets once daily plus asunaprevir 100 mg soft capsules twice daily for 24 weeks. The primary endpoint was sustained virologic response at post-treatment week 24 (SVR24).
  
  
  RESULTS
  Of the 159 patients treated, 89.3% were Chinese, 65.4% were female, and 73.6% were interferon-intolerant. Cirrhosis was present in 32.7% of patients, and 40.3% had IL28B non-CC genotypes. SVR24 was achieved by 145/159 (91.2%) patients (100% concordance with SVR12) and was similarly high in cirrhotic patients (47/52, 90.4%). SVR24 was higher in patients without baseline NS5A (L31M or Y93H) resistance-associated variants (RAVs) (137/139, 98.6%), including those with cirrhosis (43/44, 97.7%). Prevalence of baseline NS5A RAVs was low (19/159, 11.9%), particularly in mainland China (10/127, 7.9%). One death (0.6%), five serious adverse events (3.1%), and three grade 4 laboratory abnormalities (1.9%) occurred on treatment; none were considered related to study drugs. Two patients (1.3%) discontinued because of adverse events. Treatment was generally well tolerated regardless of cirrhosis status.
  
  
  CONCLUSIONS
  Daclatasvir plus asunaprevir achieved a SVR24 rate of 91.2%, rising to 98.6% in patients without baseline NS5A RAVs, and was generally well tolerated in interferon (±ribavirin)-ineligible or -intolerant patients with genotype 1b infection from mainland China, Korea, and Taiwan.
authors.affiliation: Peking University People's Hospital and Peking University Hepatology Institute, Beijing.
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.affiliation: The Sixth People's Hospital of Shenyang, Shenyang.
authors.forename: Mingxiang
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Guangzhou No.8 People's Hospital, Guangzhou.
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.affiliation: Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung.
authors.forename: Wan-Long
authors.initials: WL
authors.lastname: Chuang
authors.affiliation: Tianjin Second People's Hospital, Tianjin.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: Beijing Ditan Hospital, Capital Medical University, Beijing.
authors.forename: Wen
authors.initials: W
authors.lastname: Xie
authors.affiliation: Tangdu Hospital, Xi'an.
authors.forename: Zhansheng
authors.initials: Z
authors.lastname: Jia
authors.affiliation: The Second Xiangya Hospital of Central South University, Changsha.
authors.forename: Guozhong
authors.initials: G
authors.lastname: Gong
authors.affiliation: 302 Military Hospital of China, Beijing.
authors.forename: Yueqi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Seoul St. Mary Hospital, The Catholic University of Korea, Seoul.
authors.forename: Si Hyun
authors.initials: SH
authors.lastname: Bae
authors.affiliation: The 2nd Hospital of Nanjing, Affiliated to Medical School of South East University, Nanjing.
authors.forename: Yong-Feng
authors.initials: YF
authors.lastname: Yang
authors.affiliation: Shanghai Ruijin Hospital, Jiaotong University School of Medicine, Guangzhou.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xie
authors.affiliation: The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an.
authors.forename: Shumei
authors.initials: S
authors.lastname: Lin
authors.affiliation: Beijing Youan Hospital, Capital Medical University, Beijing.
authors.forename: Xinyue
authors.initials: X
authors.lastname: Chen
authors.affiliation: First Hospital of Jilin University, Changchun.
authors.forename: Junqi
authors.initials: J
authors.lastname: Niu
authors.affiliation: Beijing Friendship Hospital, Capital Medical University, Beijing.
authors.forename: Jidong
authors.initials: J
authors.lastname: Jia
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ.
authors.forename: Tushar
authors.initials: T
authors.lastname: Garimella
authors.affiliation: Bristol-Myers Squibb, Braine-l'Alleud.
authors.forename: Anne
authors.initials: A
authors.lastname: Torbeyns
authors.affiliation: Bristol-Myers Squibb, Wallingford, CT.
authors.forename: Fiona
authors.initials: F
authors.lastname: McPhee
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ.
authors.forename: Michelle
authors.initials: M
authors.lastname: Treitel
authors.affiliation: Bristol-Myers Squibb, Wallingford, CT.
authors.forename: Philip D
authors.initials: PD
authors.lastname: Yin
authors.affiliation: Bristol-Myers Squibb, Shanghai.
authors.forename: Ling
authors.initials: L
authors.lastname: Mo
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002219:Carbamates; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000627:therapeutic use; D007546:Isoquinolines / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D012367:RNA, Viral / Q000097:blood; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D000072230:Sustained Virologic Response; D014633:Valine / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D016898:Interferon-alpha; D007546:Isoquinolines; D011759:Pyrrolidines; D012367:RNA, Viral; D013449:Sulfonamides; D012254:Ribavirin; D014633:Valine; C549273:daclatasvir; C571889:asunaprevir
keywords: asunaprevir; daclatasvir; efficacy; hepatitis C; safety