The Changing Treatment Armamentarium for HCV - From Today to 2016

The Changing Treatment Armamentarium for HCV:
From Today to 2016

Release Date: December 12, 2013

Hello folks,
If you have time to spare during this busy holiday jump over to Clinical Care Options (CCO) for an in-depth review of approved and future HCV drugs, presented by Nezam H. Afdhal, MD, FRCPI. 

**Free registration is required

The online activity explores the most critical areas of HCV research, topics include;

The Goal of Combination Regimens
Simeprevir and Faldaprevir: Second-Generation PI-Based Therapy
Novel Classes With Peginterferon/Ribavirin in Genotype 1 HCV
The Advent of All-Oral HCV Therapy
Three- and Four-Drug Oral Regimens: Pros and Cons
Can Two-Drug Regimens Be Effective?
Treatment of Patients With HCV Genotype 2 or 3 Infection
Summary: Predicting the Future of HCV Treatment 

Excerpt: The Advent of All-Oral HCV Therapy 

Ideally, treatment approaches for HCV infection would comprise all-oral regimens. Many studies are currently evaluating regimens that comprise different combinations of oral agents. Many of these regimens include ribavirin, but given the hematologic toxicities of this agent, future HCV regimens will likely consist of combinations of oral DAAs.

NS5B PIs are the class of DAAs with which clinicians currently have the greatest experience, albeit predominantly in combination with peginterferon/ribavirin. The approval of telaprevir and boceprevir in 2011 represents the first recent advance in HCV therapy. In addition, the next-generation PIs faldaprevir and simeprevir (the latter approved in November 2013) are in advanced clinical development. These agents have high efficacy, with ≥ 4 log reductions in HCV RNA levels.

However, this class of drugs predominantly targets genotype 1 only (although some of them show efficacy against other genotypes). In addition, PIs have relatively low barriers to resistance.

NS5A inhibitors (eg, daclatasvir and ledipasvir) feature efficacy, genotype specificity, and resistance barriers that are similar to the PIs. However, the nucleotide NS5B polymerase inhibitors, such as sofosbuvir, offer good efficacy with the advantages of pangenotypic activity and high barriers to resistance; in fact, there has been almost no resistance reported in patients who have been treated with sofosbuvir. By contrast, the NS5B nonnucleoside inhibitors provide the weakest efficacy, are very genotype specific, and have an extremely low barrier to resistance; however, they may retain some utility in combination regimens despite these shortcomings.

The class of cyclophilin inhibitors includes oral interferon inducers and other host-targeting agents. The strengths of these drugs include their pangenotypic activity and high resistance barrier. Cyclophilin inhibitors that are currently in development include alisporivir and Debio 025, although the former is on clinical hold. The usefulness of these agents in HCV treatment remains to be determined.

In December 2013, the first all-oral regimen for HCV, sofosbuvir plus ribavirin, received Food and Drug Administration approval for treatment of patients infected with HCV genotype 2 or genotype 3. In 2014 and 2015, other all-oral HCV treatment regimens may be approved. Many therapeutic combinations are possible, but with the approval of both sofosbuvir and simeprevir, there is likely to be interest in exploring the off-label combination of these agents, in light of promising preliminary data. By 2016, truly pangenotypic all-oral therapies for HCV infection should be available; the most significant advance will be the development of pangenotypic NS3/4A PIs and NS5A inhibitors that have higher barriers to resistance. Such regimens should allow patients with all HCV genotypes and subtypes to be treated successfully.

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