Efficacy and safety of simeprevir and sofosbuvir with and without ribavirin in subjects with recurrent genotype 1 hepatitis C postorthotopic liver transplant: the randomized GALAXY study

Abstract

This prospective, randomized, phase 2 study in subjects with recurrent hepatitis C virus (HCV) genotype 1 postorthotopic liver transplant evaluated once-daily simeprevir 150 mg + sofosbuvir 400 mg, with and without ribavirin 1000 mg. Primary endpoint was proportion of subjects with week 12 sustained virologic response (SVR12). Thirty-three subjects without cirrhosis were randomized 1:1:1 into three arms (stratified by genotype/subtype and Q80K): Arm 1, simeprevir + sofosbuvir + ribavirin, 12 weeks; Arm 2, simeprevir + sofosbuvir, 12 weeks; Arm 3, simeprevir + sofosbuvir, 24 weeks; 13 additional subjects (two with cirrhosis, 11 without cirrhosis) entered Arm 3. All 46 subjects received at least one dose of study drug; median age, 60 years; 73.9% male; 80.4% White; 71.7% genotype/subtype 1a [12 (36.4%) of these had Q80K]; median 4.5 years post-transplant. Among randomized subjects, SVR12 was achieved by 81.8% in Arm 1, 100% in Arm 2, and 93.9% in Arm 3; two subjects did not achieve SVR12: one viral relapse (follow-up week 4; Arm 1) and one missing follow-up week 12 data. In total, five subjects had a serious adverse event, considered unrelated to treatment per investigator. Simeprevir exposure was increased relative to the nontransplant setting, but not considered clinically relevant. Simeprevir + sofosbuvir treatment, with or without ribavirin, was efficacious and well tolerated (ClinicalTrials.gov Identifier: NCT02165189).

Glecaprevir/Pibrentasvir Treatment in Liver or Kidney Transplant Patients With Hepatitis C Virus Infection

“…Until recently, treatment options for HCV were limited to interferon (IFN)‐based therapies, which had low sustained virologic response (SVR) rates and were poorly tolerated by liver transplant patients or were contraindicated in kidney transplant patients . Newer IFN‐free, all‐oral direct‐acting antiviral (DAA)–based regimens are associated with high rates of efficacy and tolerability and have demonstrated promising outcomes in clinical trials and real‐world studies in transplant patients . However, regimens currently available for transplant patients are not equally potent across all major HCV GTs, and some patient subgroups may require RBV as part of their recommended treatment, which carries a risk of anemia adverse effects .…”

“…(17) Newer IFN-free, all-oral direct-acting antiviral (DAA)-based regimens are associated with high rates of efficacy and tolerability (2) and have demonstrated promising outcomes in clinical trials and real-world studies in transplant patients. (18)(19)(20)(21)(22)(23)(24)(25)(26) However, regimens currently available for transplant patients are not equally potent across all major HCV GTs, and some patient subgroups may require RBV as part of their recommended treatment, which carries a risk of anemia adverse effects. (2) In addition, currently available DAAs have the potential for clinically significant drug-drug interactions, particularly with calcineurin inhibitors.…”

Direct‐acting antiviral agents for liver transplant recipients with recurrent genotype 1 hepatitis C virus infection: Systematic review and meta‐analysis

“…Except one study that did not report patient ethnicity, the majority of patients were Caucasian, male, with a mean age of approximately 60‐year‐old, had GT1a HCV recurrence, and received tacrolimus as part of their immunosuppressive treatment. Five different DAA combination protocols were described: SOF/SMV with or without RBV (n = 8); SOF/LDV (n = 3); ASV/SMV (n = 2); DCV/SMV with or without RBV (n = 2); PrOD (n = 1) . Detailed baseline characteristics of the included studies are provided in Tables and .…”

“…Five different DAA combination protocols were described: SOF/ SMV with or without RBV (n = 8) [13][14][15][16][17][18][19][20] ; SOF/LDV (n = 3) 21-23 ; ASV/ SMV (n = 2) 24,25 ; DCV/SMV with or without RBV (n = 2) 26,27 ; PrOD (n = 1). 28 Detailed baseline characteristics of the included studies are provided in Tables 1 and 2.…”

Clinical impact of pharmacokinetic interactions between the HCV protease inhibitor simeprevir and frequently used concomitant medications

“…Studies selected for this analysis were Janssen-sponsored clinical trials evaluating interferon-free combinations of SMV in combination with sofosbuvir (SOF) and/or daclatasvir (DCV) with or without ribavirin (RBV) ( Table 1) [14][15][16][17][18][19][20][21][22]. All studies were conducted in accordance with the 1975 Declaration of Helsinki, approved by independent ethics committees and registered with www.clinicaltrials.…”