Phase III results of Boceprevir in treatment naïve patients with chronic hepatitis C genotype 1.
BACKGROUND
Chronic hepatitis C virus infection affects approximately 2% of the world population and can result in cirrhosis and hepatocellular carcinoma. Until 2011, the standard of care (SOC) has been therapy with pegylated interferon alfa and ribavirin (PEG-IFN/RBV). Sustained virologic response rates (SVR) after SOC in patients infected with genotype 1 have been 40-50%. The development of new direct antiviral agents (DAA) is vital. The first drugs that specifically target the HCV protease have been approved in 2011. This review summarizes the results of SPRINT-2, a phase III double blind, placebo controlled study in which the efficacy and safety of Boceprevir, a new HCV protease inhibitor, was compared to SOC.


METHODS
A total of 1097 treatment-naïve, genotype 1, chronic hepatitis C patients were randomized into three different groups. All patients received a 4-week lead in phase with peginterferon alfa-2b and ribavirin. A total of 363 patients were randomized to the control group and received 44 additional weeks of PEG-IFN/RBV; of the 368 patients randomized to group 2, the response-guided treatment regimen (RGT), patients with undetectable HCV RNA through week 8 and 24 received 24 weeks of triple therapy (PEG-IFN/RBV/Boceprevir); patients whose HCV-RNA was detectable between weeks 8 and 24 but undetectable at week 24 received subsequently 20 weeks of (PEG-IFN/RBV); 366 patients in group 3 were treated with lead-in followed by triple therapy through week 48.


RESULTS
Treatment with Boceprevir triple therapy increased SVR to 63-66% compared to 38% receiving PEG-IFN/RBV therapy. Non-Black patients achieved higher SVR rates compared to Black patients. Responsiveness to interferon in the lead-in phase was predictive for SVR. SVR rates did not differ between patients randomized to RGT with Boceprevir and those treated with a fixed duration. Anaemia was the most important adverse event leading to dose reduction of RBV in 13% of controls and 21% of Boceprevir recipients.


CONCLUSIONS
Triple therapy of Boceprevir in combination with PEG-IFN 2b/RBV is more effective than SOC alone. RGT is possible without reducing the SVR rates. Management of anaemia has to be considered.
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany. manns.michael@mh-hannover.de
Michael P
MP
Manns
Antoaneta A
AA
Markova
Beatriz
B
Calle Serrano
Markus
M
Cornberg
D000740:Anemia / Q000139:chemically induced; D000998:Antiviral Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D016503:Drug Delivery Systems; D004359:Drug Therapy, Combination; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011392:Proline / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D012367:RNA, Viral / Q000032:analysis; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D015842:Serine Proteinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D015842:Serine Proteinase Inhibitors; D011092:Polyethylene Glycols; D012254:Ribavirin; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline; C100416:peginterferon alfa-2a