Safety and efficacy of viramidine versus ribavirin in ViSER2: Randomized, double-blind study in therapy-naive hepatitis C patients

• Published in: Journal of hepatology Vol. 52; no. 1; pp. 32 - 38
• Main Authors: Marcellin, Patrick, Gish, Robert G., Gitlin, Norman, Heise, Jamie, Halliman, Deanine G., Chun, Eric, Rodriguez-Torres, Maribel
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 01.01.2010; Elsevier
• Subjects: Adult; Anemia; Anemia - epidemiology; Anemia - prevention & control; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - adverse effects; Antiviral Agents - therapeutic use; Antiviral therapy; Biological and medical sciences; Diarrhea - etiology; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Endpoint Determination; Female; Gastroenterology and Hepatology; Gastroenterology. Liver. Pancreas. Abdomen; Genotype; Hepacivirus - genetics; Hepatitis C; Hepatitis C, Chronic - drug therapy; Human viral diseases; Humans; Incidence; Infectious diseases; Interferon-alpha - therapeutic use; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Polyethylene Glycols - therapeutic use; Recombinant Proteins; Ribavirin - adverse effects; Ribavirin - analogs & derivatives; Ribavirin - therapeutic use; RNA, Viral - genetics; Sustained virologic response; Treatment Outcome; Viral diseases; Viral hepatitis; Viramidine; Weight-based dosing; Antiviral therapy; peg-IFN; Anemia; CI; RBV; ITT; VRD; Weight-based dosing; ViSER2; Viramidine; SVR; AEs; HCV; Hepatitis C; Sustained virologic response; ribavirin; pegylated interferon; Viramidine’s Safety and Efficacy versus Ribavirin 2; adverse events; intent-to-treat; hepatitis C virus; confidence interval; Human; Toxicity; Hepatic disease; Hemopathy; Ribavirin; Infection; Treatment; Viral disease; Gastroenterology; Double blind study; Nucleoside analog; Digestive diseases; Antiviral; Comparative study; Viral hepatitis C
• ISSN: 0168-8278; 1600-0641; 1600-0641
• DOI: 10.1016/j.jhep.2009.10.015

Pegylated interferon (peg-IFN) plus ribavirin (standard of care for chronic hepatitis C virus [HCV]), can cause dose-limiting anemia in up to 22% of patients. Viramidine is associated with a lower incidence of anemia because of its liver-targeting properties. The efficacy and safety of viramidine versus ribavirin plus peg-IFN alfa-2a was assessed in patients with HCV. Randomized patients received peg-IFN alfa-2a 180 mcg with viramidine 600mg twice daily or weight-based doses of ribavirin 1000 or 1200mg/day. Treatment duration was based on HCV ribonucleic acid (RNA) genotype: genotype 2/3 and non-2/3 patients were treated for 24 and 48weeks, respectively. The primary efficacy end point was the non-inferiority of viramidine versus ribavirin (proportion of patients achieving sustained virologic response at week 24). The primary safety end point was the proportion of patients experiencing a hemoglobin event. In total, 962 patients received peg-IFN alfa-2a with viramidine (n=644) or ribavirin (n=318). Sustained virologic response was achieved in 40% of viramidine-treated patients and 55% of ribavirin-treated patients (difference of proportions 0.150 [95% CI, 0.09, 0.21]). Improved efficacy was seen with higher viramidine exposure on a mg/kg basis. Viramidine was significantly superior to ribavirin in hemoglobin event rates (54% vs. 80%; p<0.001). Adverse event rates were similar between groups except for diarrhea (viramidine 29.5%; ribavirin 15.7%; p<0.0001). Viramidine 600mg BID did not meet the primary efficacy non-inferiority end point but met the safety end point. Determination of a viramidine dosage that would yield superior efficacy over ribavirin is needed.