Telaprevir: A Novel NS3/4 Protease Inhibitor for the Treatment of Hepatitis C

Olga M. Klibanov, Pharm.D.; Shannon H. Williams, Pharm.D.; Lisa S. Smith, Pharm.D.; Jacqueline L. Olin, M.S., Pharm.D.; Stephen B. Vickery


Pharmacotherapy. 2011;31(10):951-974. 

In This Article

Abstract and Introduction


Hepatitis C virus (HCV) infection affects millions of people worldwide; however, standard therapy with peginterferon and ribavirin has resulted in suboptimal responses. Thus, new anti-HCV drugs with novel mechanisms of action are being studied. In particular, new drugs are being developed that target the NS3/4A protease complex. We evaluated the literature on telaprevir, a new, oral, covalent, reversible NS3/4A HCV protease inhibitor. A MEDLINE search (January 1996–July 2011) was performed to identify relevant clinical trials, and abstracts from hepatology and human immunodeficiency virus (HIV) conferences were reviewed. In large clinical trials, the addition of telaprevir to peginterferon and ribavirin resulted in high sustained virologic response rates in both treatment-naive and treatment-experienced patients infected with HCV genotype 1. Clinical data with telaprevir in the HIV-HCV coinfected population are emerging, as well as data on potential drug-drug interactions with this agent. Preliminary data describe the resistance profile of telaprevir; however, more information is needed in this evolving area. Telaprevir's most common adverse events included rash, pruritis, and anemia. Based on available data, this new anti-HCV drug will likely be widely used and may revolutionize the treatment of HCV-infected individuals.


Hepatitis C virus (HCV) infection affects over 170 million people worldwide and is the most common blood-borne infection in the United States.[1,2] Clinical trials with HCV therapy usually address four types of responses (Table 1), with sustained virologic response (SVR) being the most clinically important end point and goal of therapy for HCV-treated patients. At the time of this writing, the standard therapy for chronic HCV infection was the combination of peginterferon alfa and ribavirin.[3] This combination therapy results in approximately 55% of patients with HCV achieving SVR. The SVR rates are highest in patients with HCV genotypes 2 or 3 (70–80%), but low in patients with HCV genotype 1 (40–45%), patients coinfected with human immunodeficiency virus (HIV; 14–29%), African-Americans (19–23%), and patients with liver cirrhosis (~10%).[4–12] Because of the low response rates, the focus of clinical research for HCV infection has shifted toward direct-acting antivirals, including NS3/4 serine protease inhibitors and NS5B polymerase inhibitors (nucleoside and nonnucleoside).[13]

Final results of phase III clinical trials with the NS3/4 protease inhibitor telaprevir have been presented, and the manufacturer of telaprevir (Vertex Pharmaceuticals Inc., Cambridge, MA) submitted a new drug application to the United States Food and Drug Administration (FDA), seeking approval of telaprevir for the treatment of genotype 1 HCV, on November 23, 2010.[14] On May 23, 2011, the FDA approved telaprevir (Incivek) for the treatment of genotype 1 chronic HCV infection in adults with compensated liver disease, to be used in combination with peginterferon and ribavirin.[15]

In this review, we provide an overview of telaprevir, focusing on the drug's pharmacology, pharmacokinetics, pharmacodynamics, and the clinical data that led to its approval by the FDA. We performed a MEDLINE search (January 1996–July 2011) to identify relevant clinical trials and review articles. Abstracts and oral as well as poster presentations from meetings of the American Association for the Study of Liver Diseases, Conference on Retroviruses and Opportunistic Infections, and European Association for the Study of the Liver were also reviewed. Search terms were hepatitis C, directacting antivirals, NS3/4 serine protease inhibitors, telaprevir, and VX-950.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.