Wan-Long Chuang1, Rong-Nan Chien2, Cheng-Yuan Peng3, Ting-Tsung Chang4, Gin-Ho Lo5, I-Shyan Sheen6, Horng-Yuan Wang7, Jyh-Jou Chen8, Jenny C Yang9, Steven J Knox9, Bing Gao9, Kimberly L Garrison9, Hongmei Mo9, Phillip S Pang9, Yu-Chun Hsu10, Tsung-Hui Hu11, Chi-Jen Chu12, Jia-Horng Kao13. 1. Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. 2. Liver Research Unit, Chang Gung Memorial Hospital-Keelung, Keelung, Taiwan. 3. Department of Internal Medicine, School of Medicine, China Medical University, Taichung, Taiwan. 4. Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan. 5. Department of Medicine, E-Da Hospital, Kaohsiung, Taiwan. 6. Chang Gung Memorial Hospital and Medical College, Chang Gung University, Taoyuan, Taiwan. 7. Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan. 8. Department of Internal Medicine, Chi Mei Hospital, Liouying, Tainan, Taiwan. 9. Gilead Sciences, Inc., Foster City, California, USA. 10. Department of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan. 11. Chang Gung Medical Foundation, Kaohsiung, Taiwan. 12. Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University, School of Medicine, Taipei, Taiwan. 13. National Taiwan University College of Medicine and Hospital, Taipei, Taiwan.
Abstract
BACKGROUND AND AIM: Pegylated-interferon-alpha plus ribavirin is the current standard-of-care regimen for treating chronic hepatitis C virus (HCV) infection in Taiwan; however, interferon-based regimens can be poorly tolerated. The interferon-free, two-drug, fixed-dose combination tablet ledipasvir/sofosbuvir is approved in Europe, the USA, and Japan for treating chronic genotype 1 HCV infection. Little is known about its efficacy/safety in Taiwanese patients. METHODS: In this multicenter, open-label, phase 3b (NCT02021656) study, 85 Taiwanese patients (n = 42, treatment-naïve; n = 43, treatment-experienced) with chronic genotype 1 HCV infection (±compensated cirrhosis) received 12 weeks of ledipasvir/sofosbuvir fixed-dose combination tablet. The primary efficacy end point was the proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12). Safety and pharmacokinetic data were collected. RESULTS: The overall SVR12 rate was 98% (83/85), with 100% (42/42) and 95% (41/43) of treatment-naïve and treatment-experienced patients, respectively, achieving SVR12. There were no on-treatment virologic failures. One patient relapsed after treatment discontinuation; one patient withdrew consent on day 2. The most common treatment-emergent adverse event (AE) was headache (14%, 12/85). There was one grade 3 AE (small cell lung cancer unrelated to ledipasvir/sofosbuvir), no grade 4 AEs, and four grade 3-4 laboratory abnormalities. Only the patient with small cell lung cancer prematurely discontinued treatment. Two patients reported three serious AEs; none was considered related to ledipasvir/sofosbuvir. CONCLUSIONS: Data from this phase 3b study suggest that 12 weeks of once-daily treatment with the interferon-free, ribavirin-free regimen ledipasvir/sofosbuvir is effective and well-tolerated in Taiwanese patients with chronic genotype 1 HCV infection, irrespective of treatment history.
BACKGROUND AND AIM: Pegylated-interferon-alpha plus ribavirin is the current standard-of-care regimen for treating chronic hepatitis C virus (HCV) infection in Taiwan; however, interferon-based regimens can be poorly tolerated. The interferon-free, two-drug, fixed-dose combination tablet ledipasvir/sofosbuvir is approved in Europe, the USA, and Japan for treating chronic genotype 1 HCV infection. Little is known about its efficacy/safety in Taiwanese patients. METHODS: In this multicenter, open-label, phase 3b (NCT02021656) study, 85 Taiwanese patients (n = 42, treatment-naïve; n = 43, treatment-experienced) with chronic genotype 1 HCV infection (±compensated cirrhosis) received 12 weeks of ledipasvir/sofosbuvir fixed-dose combination tablet. The primary efficacy end point was the proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12). Safety and pharmacokinetic data were collected. RESULTS: The overall SVR12 rate was 98% (83/85), with 100% (42/42) and 95% (41/43) of treatment-naïve and treatment-experienced patients, respectively, achieving SVR12. There were no on-treatment virologic failures. One patient relapsed after treatment discontinuation; one patient withdrew consent on day 2. The most common treatment-emergent adverse event (AE) was headache (14%, 12/85). There was one grade 3 AE (small cell lung cancer unrelated to ledipasvir/sofosbuvir), no grade 4 AEs, and four grade 3-4 laboratory abnormalities. Only the patient with small cell lung cancer prematurely discontinued treatment. Two patients reported three serious AEs; none was considered related to ledipasvir/sofosbuvir. CONCLUSIONS: Data from this phase 3b study suggest that 12 weeks of once-daily treatment with the interferon-free, ribavirin-free regimen ledipasvir/sofosbuvir is effective and well-tolerated in Taiwanese patients with chronic genotype 1 HCV infection, irrespective of treatment history.
Authors: Massimo Giuseppe Colombo; Erkin Isakovich Musabaev; Umed Yusupovich Ismailov; Igor A Zaytsev; Alexander V Nersesov; Igor Anatoliyevich Anastasiy; Igor Alexandrovich Karpov; Olga A Golubovska; Kulpash S Kaliaskarova; Ravishankar Ac; Sanjay Hadigal Journal: World J Gastroenterol Date: 2019-08-07 Impact factor: 5.742
Authors: Elise J Smolders; Anouk M E Jansen; Peter G J Ter Horst; Jürgen Rockstroh; David J Back; David M Burger Journal: Clin Pharmacokinet Date: 2019-10 Impact factor: 6.447
Authors: Michael J Zoratti; Ayesha Siddiqua; Rita E Morassut; Dena Zeraatkar; Roger Chou; Judith van Holten; Feng Xie; Eric Druyts Journal: EClinicalMedicine Date: 2020-01-05