Phase 3 study shows that combination of elbasvir and grazoprevir is highly efficacious in hepatitis C virus (HCV) infected patients with inherited blood disorders.
Direct-acting antiviral (DAA) therapy has become the gold standard for treatment of hepatitis C virus (HCV) infections since its introduction in 2011. DAA therapy has proven effective in hard to treat patient populations, including those co-infected with HIV and HCV. However, very little data is available on the efficacy of DAA therapy on HCV patients with inherited blood disorders (IBLDs). In a study published in the Journal of Hepatology, principal investigator Vito Di Marco, MD, professor of gastroenterology at the University of Palermo in Italy, and his colleagues examine the efficacy of a ribavirin-free DAA therapy regimen on HCV patients with either sickle cell disease, thalassemia, or hemophilia/von Willebrand disease.
The study utilized a combination of 2 DAA drugs, elbasvir (EBR), a nonstructural 5A inhibitor, and grazoprevir (GZR), an HCV NS3/4A protease inhibitor. This combination has been approved by the US Food and Drug Administration (FDA) for the treatment of HCV patients with genotypes 1 or 4 and has been shown to be highly effective even in patients with liver cirrhosis and chronic kidney disease. The phase 3, randomized study, called C-EDGE IBLD, included female and male patients with HCV genotypes 1, 4, or 6. Patients with compensated liver cirrhosis and those co-infected with HIV were also eligible for the study. Furthermore, patients that had never received HCV treatment, those that previously received interferon-based therapy, and those that were intolerant to interferon-based therapy plus ribavirin were included. Patients were excluded if they had decompensated liver disease, were co-infected with the hepatitis B virus, or had a history of substance abuse or a history of cancer.
Patients were randomly assigned to 2 groups, those that received immediate treatment and the placebo group, which was given the treatment later. Patients, as well as investigators, were unaware of the assignments each patient received. Those in the immediate-treatment group received 50 milligrams of EBR and 100 milligrams of GZR for 12 weeks. Those in the placebo group received placebo tablets for 12 weeks, followed by a month-long follow-up period, and then they received 12 weeks of EBR and GZR. The primary endpoint of the study was if patients reached a sustained virologic response (SVR) after 12 weeks of treatment.
The study consisted of 159 patients that were randomly assigned to the 2 groups. A total of 107 received the treatment while 52 were in the placebo group. The majority of patients were white males with HCV genotype 1 infection. The breakdown of IBLDs was as follows: 18% of patients had sickle cell disease, 38% had thalassemia, and 44% had hemophilia or von Willebrand disease. In the treatment group, 100 out of the 107 patients achieved SVR in 12 weeks. The remaining 7 patients who did not reach SVR12 either relapsed (6 patients) or were lost to follow-up (1 patient). In addition, 94.7% of patients with sickle cell disease achieved SVR12, while 97.6% and 89.4% of patients with thalassemia and hemophilia or von Willebrand disease achieved SVR12, respectively.
The authors reported similar safety profiles for patients in the treatment and control group with the most frequent side effects reported being headaches, fatigue, nausea, and asthenia. Serious side effects were reported by 3 patients in the experimental group and 6 patients in the placebo group, with the majority of side effects not being attributed to the drug. Overall, the authors conclude that the combination of EBR plus GZR is highly effective, with 93.5% of patients achieving SVR12 as well as safe and well-tolerated in HCV patients with IBLDs.
Samar Mahmoud graduated from Drew University in 2011 with a BA in Biochemistry and Molecular Biology. After two years of working in the industry as a Quality Control Technician for a blood bank, she went back to school and graduated from Montclair State University in 2016 with an MS in Pharmaceutical Biochemistry. She is currently pursuing her PhD in Molecular and Cellular Biology at the University of Massachusetts at Amherst.