TY - JOUR
T1 - Sofosbuvir–velpatasvir plus ribavirin in Japanese patients with genotype 1 or 2 hepatitis C who failed direct-acting antivirals
AU - Izumi, Namiki
AU - Takehara, Tetsuo
AU - Chayama, Kazuaki
AU - Yatsuhashi, Hiroshi
AU - Takaguchi, Koichi
AU - Ide, Tatsuya
AU - Kurosaki, Masayuki
AU - Ueno, Yoshiyuki
AU - Toyoda, Hidenori
AU - Kakizaki, Satoru
AU - Tanaka, Yasuhito
AU - Kawakami, Yoshiiku
AU - Enomoto, Hirayuki
AU - Ikeda, Fusao
AU - Jiang, Deyuan
AU - De-Oertel, Shampa
AU - McNabb, Brian L.
AU - Camus, Gregory
AU - Stamm, Luisa M.
AU - Brainard, Diana M.
AU - McHutchison, John G.
AU - Mochida, Satoshi
AU - Mizokami, Masashi
N1 - Funding Information:
Funding Funding for this study was provided by Gilead Sciences, Inc.
Funding Information:
We thank the patients and their families as well as the study-site personnel. Writing assistance was provided by Jennifer King, Ph.D., of August Editorial. Namiki Izumi: Gilead, AbbVie, Otsuka, Shionogi, and Bayer. Consultant: Kowa, Shionogi, Gilead, AbbVie, and Eizai (Speaker). Tetsuo Takehara: Gilead (Research support funding and lecturer). Kazuaki Chayama: AbbVie, MSD, BMS, and Gilead (Speaker). Hiroshi Yatsuhashi: Chugai (Research grant). Koichi Takaguchi: AbbVie, Bristol-Myer Squib, Astra-Zeneka KK (Speaker). Tatsuya Ide: Gilead, and Abbvie (Speaker). Masayuki Kurosaki: AbbVie, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Otsuka, and Toray (Speaker). AbbVie, Gilead Sciences, GlaxoSmithKline, and Otsuka (Scientific advisor). Yoshiyuki Ueno: Gilead Sciences, Inc, BMS, Abbvie, MSD (Research grant). Hidenori Toyoda: Gilead Sciences, AbbVie, Bristol-Meyers Squibb, MSD, Sysmex, WAKO, Bayer Pharma, and Abbott (Speaker). Satoru Kakizaki: AbbVie, BMS, Gilead, and MSD. Research grant: AbbVie, BMS, Gilead, and MSD (Speaker). Yasuhito Tanaka: Gilead and Janssen (Advisory committees or review panels). Chugai Pharmaceutical Co., Ltd., Abbvie, Bristol-Myers Squibb, Janssen, and Gilead Sciences (Grant/research support). Bristol-Myers Squibb and Gilead Sciences (Speaking and Teaching). Yoshiiku Kawakami: None. Hirayuki Enomoto: None. Fusao Ikeda: None. Satoshi Mochida: SRL Inc. (Royalties). Bristol-Myers Squibb, Toray Medical Co. Ltd., Ajinomoto Pharmaceuticals Co. Ltd., MSD K.K. (Lecture Fees). Bristol-Myers Squibb, Tanabe Mitsubishi Pharma Co. Ltd., MSD K.K. (Consigned/joint research expenses). Bristol-Myers Squibb, MSD K.K., Toray Medical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., and Takeda Phamaceutical Co. Ltd. (Scholarship Donations). Masashi Mizokami: Gilead and Sysmex (Speaker). Gilead and Sysmex (Consultant). Deyuan Jiang, Shampa De-Oertel, Gregory Camus, Luisa M. Stamm, Diana M. Brainard, and John G. McHutchison?are employees of and own stock in Gilead Sciences, Inc. Brian McNabb owns stock in Gilead Sciences, and was an employee of Gilead at the time which the study was conducted. He is an employee of and owns stock in DocMatter.com.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/7/1
Y1 - 2018/7/1
N2 - Background/purpose: In Japan, there is a growing population of patients with chronic hepatitis C virus (HCV) infection who failed a direct-acting antiviral (DAA)-based regimen. In this Phase 3 study, we evaluated sofosbuvir–velpatasvir plus ribavirin in Japanese patients with genotype 1 or 2 HCV infection who previously received DAAs. Methods: Patients were randomized 1:1 to receive sofosbuvir–velpatasvir plus ribavirin for 12 or 24 weeks. Randomization was stratified by HCV genotype and presence of cirrhosis. The primary endpoint was sustained virologic response 12-week post-treatment (SVR12). Results: Of 117 participants, 81% had HCV genotype 1 infection, 33% had cirrhosis, and 95% had NS5A resistance-associated substitutions (RAS) at baseline. Overall, SVR12 rates were 97% (58/60; 95% CI 88–100%) with 24 weeks of treatment and 82% (47/57; 95% CI 70–91%) with 12 weeks. For HCV genotype 1 and 2 infected patients, the SVR12 rates with 24 weeks of treatment were 98% and 92%, respectively. In both treatment groups, SVR12 rates in HCV genotype 1 patients were statistically superior to a historical control rate of 50% (p < 0.001). For patients with NS5A RASs at baseline, 85% (46/54) in the 12-week group and 96% (54/56) in the 24-week group achieved SVR12. The most common adverse events were upper respiratory tract viral infection, anemia, and headache. Three (2.6%) patients discontinued treatment because of adverse events. Conclusion: Sofosbuvir–velpatasvir plus ribavirin was highly effective and well tolerated in Japanese patients who previously failed a DAA-based regimen. Baseline NS5A RASs did not affect treatment outcomes.
AB - Background/purpose: In Japan, there is a growing population of patients with chronic hepatitis C virus (HCV) infection who failed a direct-acting antiviral (DAA)-based regimen. In this Phase 3 study, we evaluated sofosbuvir–velpatasvir plus ribavirin in Japanese patients with genotype 1 or 2 HCV infection who previously received DAAs. Methods: Patients were randomized 1:1 to receive sofosbuvir–velpatasvir plus ribavirin for 12 or 24 weeks. Randomization was stratified by HCV genotype and presence of cirrhosis. The primary endpoint was sustained virologic response 12-week post-treatment (SVR12). Results: Of 117 participants, 81% had HCV genotype 1 infection, 33% had cirrhosis, and 95% had NS5A resistance-associated substitutions (RAS) at baseline. Overall, SVR12 rates were 97% (58/60; 95% CI 88–100%) with 24 weeks of treatment and 82% (47/57; 95% CI 70–91%) with 12 weeks. For HCV genotype 1 and 2 infected patients, the SVR12 rates with 24 weeks of treatment were 98% and 92%, respectively. In both treatment groups, SVR12 rates in HCV genotype 1 patients were statistically superior to a historical control rate of 50% (p < 0.001). For patients with NS5A RASs at baseline, 85% (46/54) in the 12-week group and 96% (54/56) in the 24-week group achieved SVR12. The most common adverse events were upper respiratory tract viral infection, anemia, and headache. Three (2.6%) patients discontinued treatment because of adverse events. Conclusion: Sofosbuvir–velpatasvir plus ribavirin was highly effective and well tolerated in Japanese patients who previously failed a DAA-based regimen. Baseline NS5A RASs did not affect treatment outcomes.
KW - Antiviral resistance
KW - DAA-experienced
KW - NS5A inhibitor
KW - NS5B polymerase inhibitor
KW - Salvage therapy
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U2 - 10.1007/s12072-018-9878-6
DO - 10.1007/s12072-018-9878-6
M3 - Article
C2 - 30030720
AN - SCOPUS:85050319613
SN - 1936-0533
VL - 12
SP - 356
EP - 367
JO - Hepatology International
JF - Hepatology International
IS - 4
ER -