Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Drugs
Published in: Drugs 6/2015

01-04-2015 | Adis Drug Evaluation

Ledipasvir/Sofosbuvir: A Review of Its Use in Chronic Hepatitis C

Author: Gillian M. Keating

Published in: Drugs | Issue 6/2015

Login to get access

Abstract

The single-tablet regimen of the hepatitis C virus (HCV) NS5A inhibitor ledipasvir and the HCV NS5B polymerase inhibitor sofosbuvir (ledipasvir/sofosbuvir; Harvoni®) was recently approved in the US and the EU. The phase III ION trials included treatment-naive (ION-1 and -3) or treatment-experienced (ION-2) patients with chronic HCV genotype 1 infection (≈20 % of patients in ION-1 and -2 had cirrhosis, whereas no patient in ION-3 had cirrhosis). A sustained virological response 12 weeks’ post-treatment (SVR12) was seen in 99 % of treatment-naive patients receiving ledipasvir/sofosbuvir for 12 weeks in ION-1, with no additional benefit conferred by the addition of ribavirin or extending the treatment duration to 24 weeks. Moreover, in ION-3, an 8-week regimen achieved an SVR12 rate of 94 % overall and 97 % in the subgroup of patients with a baseline HCV RNA level of <6 million IU/mL. SVR12 rates of 94 and 99 % were seen in treatment-experienced patients who received ledipasvir/sofosbuvir for 12 and 24 weeks in ION-2. Data also support the use of ledipasvir/sofosbuvir in chronic HCV genotype 4 infection, in HCV and HIV co-infection and, in combination with ribavirin, in patients with chronic HCV genotype 1 or 4 infection who have decompensated cirrhosis or are liver transplant recipients and in chronic HCV genotype 3 infection. Oral ledipasvir/sofosbuvir was generally well tolerated. In conclusion, ledipasvir/sofosbuvir is an important new single-tablet regimen that represents a significant advance in the treatment of chronic hepatitis C.
Literature
1.
2.
3.
Hebner C, Lee Y-J, Han B, et al. In vitro pan-genotypic and combination activity of sofosbuvir (GS-7977) in stable replicon cell lines [abstract no. 1875]. Hepatology. 2012;56(4 Suppl):1066A.
4.
Afdhal N, Zeuzem S, Kwo P, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370(20):1889–98.CrossRefPubMed
5.
Afdhal N, Reddy KR, Nelson DR, et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014;370(16):1483–93.CrossRefPubMed
6.
Kowdley KV, Gordon SC, Reddy KR, et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014;370(20):1879–88.CrossRefPubMed
7.
Sarrazin C, Dvory-Sobol H, Svarovskaia ES, et al. Baseline and post-baseline resistance analyses of phase 2/3 studies of ledipasvir/sofosbuvir ± RBV [abstract no. 1926 plus poster]. Hepatology. 2014;60(4 Suppl):1128A.
8.
Mizokami M, Takehara T, Yokosuka O, et al. 100 % SVR12 in Japanese patients with chronic genotype 1 hepatitis C virus infection receiving ledipasvir/sofosbuvir fixed dose combination for 12 weeks: results from a multicenter phase 3 study [abstract no. 1929 plus poster]. Hepatology. 2014;60(4 Suppl):1130A.
9.
German P, Mathias A, Yang JC, et al. The pharmacokinetics of ledipasvir, an HCV specific NS5A inhibitor in HCV-uninfected subjects with moderate and severe hepatic impairment [abstract no. 467 plus poster]. Hepatology. 2013;58(4 Suppl 1):432A.
10.
Mogalian E, Mathias A, Yang JC, et al. The pharmacokinetics of ledipasvir, an HCV specific NS5A inhibitor, in HCV-uninfected subjects with severe renal impairment [abstract no. 1952]. Hepatology. 2014;60(4 Suppl):1145A–6A.
11.
Kirby B, German P, Shen G, et al. No differences in the pharmacokinetics of sofosbuvir (GS-7977) and sofosbuvir/ledipasvir (GS-7977/GS-5885) fixed dose combination between Japanese and Caucasians [abstract no. 954]. Hepatol Int. 2013;7(Suppl 1):S375–6.
12.
German P, Pang PS, Fang L, et al. Drug-drug interaction profile of the fixed-dose combination tablet ledipasvir/sofosbuvir [abstract no. 1976 plus poster]. Hepatology. 2014;60(4 Suppl):1162A.
13.
German P, Garrison K, Pang PS, et al. Drug–drug interactions between anti-HCV regimen ledipasvir/sofosbuvir and antiretrovirals [abstract no. 82]. In: 2015 Conference on Retroviruses and Opportunistic Infections. 2015.
14.
German P, Moorehead L, Pang P, et al. Lack of a clinically important pharmacokinetic interaction between sofosbuvir or ledipasvir and hormonal oral contraceptives norgestimate/ethinyl estradiol in HCV-uninfected female subjects. J Clin Pharmacol. 2014;54(11):1290–8.CrossRefPubMed
15.
Mathias A, Cornpropst M, Clemons D, et al. No clinically significant pharmacokinetic drug-drug interactions between sofosbuvir (GS-7977) and the immunosuppressants, cyclosporine A or tacrolimus in healthy volunteers [abstract no. 1869 plus poster]. Hepatology. 2012;56(4 Suppl):1063A–4A.
16.
Flamm SL, Everson GT, Charlton M, et al. Ledipasvir/sofosbuvir with ribavirin for the treatment of HCV in patients with decompensated cirrhosis: preliminary results of a prospective multicenter study [abstract no. 239 plus slide presentation]. Hepatology. 2014;60(4 Suppl):320A–1A.
17.
Reddy KR, Everson GT, Flamm SL, et al. Ledipasvir/sofosbuvir with ribavirin for the treatment of HCV in patients with post-transplant recurrence: preliminary results of a prospective, multicenter study [abstract no. 8 plus slide presentation]. Hepatology. 2014;60(4 Suppl):200A–1A.
18.
Gane EJ, Stedman CA, Hyland RH, et al. Efficacy of nucleotide polymerase inhibitor sofosbuvir plus the NS5A inhibitor ledipasvir or the NS5B non-nucleoside inhibitor GS-9669 against HCV genotype 1 infection. Gastroenterology. 2014;146(3):736–43.CrossRefPubMed
19.
Lawitz E, Poordad FF, Pang PS, et al. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet. 2014;383(9916):515–23.CrossRefPubMed
20.
Naggie S, Cooper C, Saag MS, et al. Ledipasvir/sofosbuvir for 12 weeks in patients coinfected with HCV and HIV-1 [abstract no. 152LB]. In: 2015 Conference on Retroviruses and Opportunistic Infections. 2015.
21.
Bernstein DE, Mangia A, Brau N, et al. Concordance between SVR4, SVR12 and SVR24 in genotype 1 HCV-infected patients who received all oral fixed-dose combination ledipasvir/sofosbuvir with or without ribavirin in phase 3 clinical trials [abstract no. 1947 plus slide presentation]. Hepatology. 2014;60(4 Suppl):1142A–3A.
22.
Jacobson IM, Kwo PY, Kowdley KV, et al. Virologic response rates to all oral fixed-dose combination ledipasvir/sofosbuvir regimens are similar in patients with and without traditional negative predictive factors in phase 3 clinical trials [abstract no. 1945 plus poster]. Hepatology. 2014;60 (4 Suppl):1141A–2A.
23.
Gordon SC, Fried MW, Kwo PY, et al. No differences in the efficacy of fixed-dose combination ledipasvir/sofosbuvir in patients according to fibrosis stage determined by liver biopsy or laboratory biomarker in phase 3 clinical trials [abstract no. 1958 plus poster]. Hepatology. 2014;60(4 Suppl):1149A–50A.
24.
Younossi Z, Stepanova M, Marcellin P, et al. Sustained virologic response with ledipasvir (LDV) and sofosbuvir (SOF) regimens lead to substantial improvement in patient-reported outcomes (PROs) among chronic hepatitis C (CHC) patients with early hepatic fibrosis as well as those with advanced hepatic fibrosis [abstract no. 1445 plus poster]. Hepatology. 2014;60(4 Suppl):892A–3A.
25.
Younossi ZM, Stepanova M, Marcellin P, et al. Treatment with ledipasvir and sofosbuvir improves patient-reported outcomes: results from the ION-1, 2 and 3 clinical trials. Hepatology. 2015. doi:10.​1002/​hep.​27724.
26.
Osinusi A, Townsend K, Kohli A, et al. Virologic response following combined ledipasvir and sofosbuvir administration in patients with HCV genotype 1 and HIV co-infection. JAMA. 2015. doi:10.​1001/​jama.​2015.​1373.
27.
Gane E, Hyland RH, Pang P, et al. Sofosbuvir/ledipasvir fixed dose combination is safe and effective in HCV infected populations including decompensated patients and patients with prior sofosbuvir treatment experience [abstract no. 238 plus slide presentation]. Gastroenterology. 2014;146(5 Suppl 1):S904–S5.
28.
Kapoor R, Kohil A, Sidharthan S, et al. All oral treatment for genotype 4 chronic hepatitis C infection with sofosbuvir and ledipasvir: interim results from the NIAID SYNERGY trial [abstract no. 240 plus slide presentation]. Hepatology. 2014;60(4 Suppl):321A.
29.
Gane EJ, Hyland RH, An D, et al. High efficacy of LDV/SOF regimens for 12 weeks for patients with HCV genotype 3 or 6 infection [abstract no. LB-11 plus poster]. Hepatology. 2014;60(1 Suppl).
30.
Alqahtani S, Afdhal NH, Zeuzem S, et al. Safety of ledipasvir/sofosbuvir with and without ribavirin for the treatment of patients with chronic HCV genotype 1 infection: an analysis of the phase 3 ION trials [abstract no. 1944 plus poster]. Hepatology. 2014;60 (4 Suppl):1140A–1A.
31.
Bourlière M, Sulkowski MS, Omata M, et al. An integrated safety and efficacy analysis of >500 patients with compensated cirrhosis treated with ledipasvir/sofosbuvir with or without ribavirin [abstract no. 82 plus slide presentation]. Hepatology. 2014;60(4 Suppl):239A.
32.
33.
Petersen T, Gordon LA, Townsend K, et al. Pill burden and treatment length reduce adherence to IFN-free hepatitis C therapy in an urban cohort [abstract no. 667]. Top Antivir Med. 2014;22(e-1):331–2.
34.
35.
Lawitz E, Poordad F, Hyland RH, et al. High rates of SVR in patients with genotype 1 HCV infection and cirrhosis after treatment with ledipasvir/sofosbuvir + ribavirin or ledipasvir/sofosbuvir + GS-9669 for 8 weeks [abstract no. 1948]. Hepatology. 2014;60(4 Suppl):1143A.
36.
Osinusi A, Kohli A, Marti MM, et al. Re-treatment of chronic hepatitis C virus genotype 1 infection after relapse: an open-label pilot study. Ann Intern Med. 2014;161(9):634–8.CrossRefPubMed
37.
Wyles DL, Pockros PJ, Yang JC, et al. Retreatment of patients who failed prior sofosbuvir-based regimens with all oral fixed-dose combination ledipasvir/sofosbuvir plus ribavirin for 12 weeks [abstract no. 235 plus slide presentation]. Hepatology. 2014;60(4 Suppl):317A–8A.
38.
Osinusi A, Meissner EG, Lee YJ, et al. Sofosbuvir and ribavirin for hepatitis C genotype 1 in patients with unfavorable treatment characteristics: a randomized clinical trial. JAMA. 2013;310(8):804–11.CrossRefPubMedCentralPubMed
39.
Hoofnagle JH, Sherker AH. Therapy for hepatitis C: the costs of success. N Engl J Med. 2014;370(16):1552–3.CrossRefPubMed
40.
Younossi ZM, Park H, Saab S, et al. Cost-effectiveness of all-oral ledipasvir/sofosbuvir regimens in patients with chronic hepatitis C virus genotype 1 infection. Aliment Pharmacol Ther. 2015;41(6):544–63.CrossRefPubMed
Metadata
Title
Ledipasvir/Sofosbuvir: A Review of Its Use in Chronic Hepatitis C
Author
Gillian M. Keating
Publication date
01-04-2015
Publisher
Springer International Publishing
Published in
Drugs / Issue 6/2015
Print ISSN: 0012-6667
Electronic ISSN: 1179-1950
DOI
https://doi.org/10.1007/s40265-015-0381-2

Other articles of this Issue 6/2015

Drugs 6/2015 Go to the issue

Review Article

Depression in Type 2 Diabetes Mellitus: Prevalence, Impact, and Treatment

Leading Article

The Role of Anti-PD-1/PD-L1 Agents in Melanoma: Progress to Date

R&D Insight Report

Safinamide: First Global Approval

Adis Drug Evaluation

Albiglutide: A Review of Its Use in Patients with Type 2 Diabetes Mellitus

Review Article

Clinical Association Between Pharmacogenomics and Adverse Drug Reactions

R&D Insight Report

Panobinostat: First Global Approval