Emerging therapies for hepatitis C virus
ABSTRACT Currently, 170 million people worldwide are affected by the HCV. Chronic HCV infection is amongst the leading causes of chronic liver disease and its complications such as cirrhosis and hepatocellular carcinoma, making it the most common reason for liver transplantation. The current standard of treatment for HCV is pegylated IFN-α plus ribavirin. This treatment, when administered for the standard duration, allows sustained virological response (SVR) in ∼ 50% of patients infected with HCV and about 40% for HCV genotype 1, the most prevalent form of HCV in the US. SVR rates for populations with co-morbidities (patients with chronic renal disease) and certain ethnic backgrounds (African Americans and Hispanics) are lower. Given the high prevalence and relatively low cure rates of current antiviral therapy, the burden of HCV is enormous.
Faced with this urgent and growing medical need, research into novel therapeutic compounds for the treatment of HCV is a rapidly growing industry. Several novel compounds are in advanced stages of clinical development, such as HCV protease inhibitors (particularly those against NS3-4A protease), HCV polymerase inhibitors (including both nucleoside and non-nucleoside analogs) and cyclophilin inhibitors.
HCV treatment has seen many advances in the last decade and the discovery process has been fraught with both successes and disappointments. Through a process of rigorous research, the current late stage novel HCV therapeutics seem to have overcome some of the obstacles met by their early predecessors and offer the promise of meeting the shortfalls of the current standard of treatment.
Data from clinical trials are encouraging and suggest that combination therapies of these novel agents may have the potential to shorten treatment duration and increase viral clearance when used in conjunction with pegylated IFN-α and ribavirin.
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ABSTRACT: Successful treatment with antiviral therapy could potentially reduce morbidity and mortality in patients with hepatitis C virus (HCV) infection. However, at the population level, these benefits may be offset by a limited number of patients who have access to antiviral treatment. Using data from the National Health and Nutrition Examination Survey conducted in 2005-2008, we analyzed the health insurance status and treatment candidacy of HCV-positive (HCV+) individuals. A total of 10,582 subjects were examined; of those, 1.16% had detectable HCV RNA and were defined as HCV+. The HCV+ patients were less likely to be insured than HCV-negative individuals (61.2% versus 81.2%; P = 0.004). Among those with health insurance, HCV+ patients were less likely to have private insurance, whereas the coverage by Medicare/Medicaid and other government-sponsored plans was similar to the rest of the population. In multivariate analysis, HCV infection was an independent predictor of being uninsured even after adjustment for demographic disparity of the HCV+ cohort (odds ratio, 0.43; 95% confidence interval, 0.24-0.78). Of all HCV+ patients, 66.7% were eligible for anti-HCV treatment. However, only 54.3% of HCV+ treatment candidates had any type of insurance coverage. Finally, only 36.3% of HCV+ patients were potentially eligible for treatment and had health insurance. CONCLUSION: A high proportion of HCV+ patients are currently uninsured, and many have publicly funded health insurance. Among those who could be candidates for treatment, the rate of insurance coverage is even lower. These findings can have important implications for health insurance coverage of these patients under the new health care reform legislation in the United States.Hepatology 03/2011; 53(3):737-45. DOI:10.1002/hep.24131 · 11.19 Impact Factor
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ABSTRACT: Compound 1 was identified as a HCV replication inhibitor from screening/early SAR triage. Potency improvement was achieved via modulation of substituent on the 5-azo linkage. Due to potential toxicological concern, the 5-azo linkage was replaced with 5-alkenyl or 5-alkynyl moiety. Analogs containing the 5-alkynyl linkage were found to be potent inhibitors of HCV replication. Further evaluation identified compounds 53 and 63 with good overall profile, in terms of replicon potency, selectivity and in vivo characteristics. Initial target engagement studies suggest that these novel carbanucleoside-like derivatives may inhibit the HCV replication complex (replicase).Bioorganic & medicinal chemistry letters 12/2011; 22(2):1160-4. DOI:10.1016/j.bmcl.2011.11.091 · 2.33 Impact Factor
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ABSTRACT: Recent trials evaluated the safety and efficacy of two protease inhibitors, boceprevir (Victrelis) and telaprevir (Incivek), added to standard care with pegylated interferon and ribavirin, in patients with chronic hepatitis C virus (HCV) infection. These drugs open the door for triple therapy and other new therapies involving combinations of other direct-acting antiviral agents to become the new standard of care for this population.Cleveland Clinic Journal of Medicine 03/2012; 79(3):213-22. DOI:10.3949/ccjm.79a.11082 · 3.37 Impact Factor