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

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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.

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Disclosure

The preparation of this review was not supported by any external funding. Gillian Keating is a salaried employee of Adis/Springer. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit.

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    Gillian M. Keating

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Correspondence to Gillian M. Keating.

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The manuscript was reviewed by: M. Buti, Department of Hepatology, Hospital General Universitari Vall d’Hebron, Barcelona, Spain; M. Romero-Gómez, Unit for Clinical Management of Digestive Diseases and CIBERehd, Valme University Hospital, University of Seville, Seville, Spain; C. A. Stedman, University of Otago Christchurch and Department of Gastroenterology, Christchurch Hospital, Christchurch, New Zealand.

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Keating, G.M. Ledipasvir/Sofosbuvir: A Review of Its Use in Chronic Hepatitis C. Drugs 75, 675–685 (2015). https://doi.org/10.1007/s40265-015-0381-2

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