Candidates for new therapeutic approaches
The current Standard of Care (SoC) combination therapy for chronic hepatitis C (CHC) is limited by its insufficient efficacy in some patient groups, the drug side-effects and contraindications and the high associated costs. There are an increasing number of therapeutic failures, with patients who do not respond or who relapse with the available SoC. Assuming there are no changes in the type of treatment, the projection for the next 20 years is that the total number of patients with advanced liver disease will be 4-fold higher than today, with nonresponders far exceeding those actively treated and total medical costs being expected to triple. Tadalafil generic online
New therapeutic approaches will be especially important for
– Patients with significant adverse events (AEs) associated with SoC therapy. In clinical trials, AEs imposed dosereduction in more than 60% of the cases and treatment withdrawal in 10–15% of cases; in clinical practice, the rate of treatment discontinuation is substantially higher.
– Treatment-naive and challenging populations. These include patients infected with viral genotypes 1 and 4 (which are refractory to the current SoC), especially those with unfavorable pre-treatment characteristics (high VL, advanced fibrosis, IL28B unfavorable genotypes CT or TT), as well as other “difficult-to-treat” populations detailed in chapter 3.
– Relapsers and nonresponders of all genotypes. Different treatment options that can either augment the efficacy of current therapy or potentially result in PegIFNand/ or ribavirin (RBV)-sparing regimens are being extensively studied. New emerging therapies include
– improved interferon (IFN) alfa formulations (to enhance efficacy and ease of administration)
– alternative RBV-like molecules (to reduce toxicity)
– direct-acting antivirals (DAAs) that target specific key steps of the viral life cycle
New IFN formulations
New interferons are currently being developed to offer enhanced activity, improved AE profiles and, hopefully, better tolerability compared with currently available ones. Given the dependence of treatment success on patients adherence, the development of longer-acting IFN formulations, with improved pharmacokinetic profiles, is an important focus of HCV therapy. Their main advantages consist in maintenance of viral suppression across a longer dosing interval, avoidance of inter-dose trough, and reduced dosing frequencies (twice or even once per month compared to once per week for the current pegylated interferons (PegIFNs). Although studies about improved formulations of interferons have been focused on HCV genotype 1, their administration can be also valuable for genotype 2 or 3 infected patients. In easy-to-treat patients (infected with genotype 2 or 3), the duration of treatment can be reduced to 12 weeks if a rapid virologic response (RVR) is obtained. This can translate into a very convenient therapeutic regimen of only 3 injections, if longer-acting IFNs, with monthly dosing, are going to be used.