Simeprevir

Information about Simeprevir

Simeprevir is an oral, direct acting hepatitis C virus (HCV) protease inhibitor that is used in combination with other antiviral agents in the treatment of chronic hepatitis C, genotypes 1 and 4.

Liver safety of Simeprevir

Simeprevir has been linked to isolated, rare instances of mild, acute liver injury during treatment and to occasional cases of hepatic decompensation in patients with preexisting cirrhosis.

History of Simeprevir

The hepatitis C virus is a small RNA virus that is a major cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma in the United States as well as worldwide. Various approaches to antiviral therapy of chronic hepatitis C have been developed, starting in the 1980s with interferon alfa which was replaced in the 1990s by long acting forms of interferon (peginterferon), to which was added the oral nucleoside analogue, ribavirin. Between 2010 and 2015, several potent oral, direct acting anti-HCV agents were developed and combinations of these found to have marked activity against the virus, allowing for highly effective therapy without use of interferon with treatment courses of 12 to 24 weeks only. These direct acting agents included HCV protease (NS3/4) inhibitors, structural replication complex (NS5A) inhibitors and the HCV RNA polymerase (NS5B) inhibitors.

Mechanism of action of Simeprevir

The HCV protease inhibitors block the activity of the viral encoded protease that is essential in the posttranslational modification of the viral polypeptide, cleaving it into a series of structural and nonstructural (NS: enzyme) regions. The HCV proteases that have been developed are polypeptide-like molecules, modified amino acids that that resemble the specific amino acid sequence that the protease cleaves and act as competitive inhibitors of the protease enzyme. At least four HCV protease inhibitors (all having the suffix: previrs) have been approved for use in the United States: boceprevir [2012], telaprevir [2012], simeprevir [2013] and paritaprevir [2014].

Simeprevir (sim e' pre vir) was the third HCV protease inhibitor to become clinically available for therapy of hepatitis C. Like other HCV protease inhibitors, simeprevir blocks the activity of the viral encoded protease (HCV nonstructural [NS] region 3/4) that is essential in the posttranslational modification of the viral polypeptide that is cleaved into a series of structural and nonstructural (enzyme) regions. When used by itself, it results in rapid inhibition of HCV RNA levels, but resistance develops rapidly in a high proportion of patients. When combined with peginterferon and ribavirin, it was shown to provide a sustained inhibition of HCV RNA with a low rate of antiviral resistance. When given for 24 to 48 weeks, triple therapy using simeprevir increased the sustained virological response (SVR) rate from 40% to 50% (peginterferon and ribavirin alone) to 65% to 75% in patients with genotype 1. Even higher rates of response were found when simeprevir was combined with the HCV polymerase inhibitor sofosbuvir in an all-oral, interferon free regimen for 12 weeks.

FDA approval information for Simeprevir

Simeprevir was approved for use in the United States in 2013 for patients with chronic hepatitis C, genotypes 1 and 4, in combination with peginterferon and ribavirin or as an all-oral regimen with sofosbuvir. Simeprevir is available in 150 mg capsules under the brand name Olysio (formerly TMC435), and the recommended dose is 150 mg once daily for 12 weeks. Common side effects include rash, photosensitivity, pruritus, nausea, headache, muscle aches and abdominal discomfort.

The following are drugs for Hepatitis C:

Interferon Based Therapies

• Alpha Interferon and Peginterferon, Ribavirin

HCV NS5A Inhibitors

• Daclatasvir, Elbasvir, Ledipasvir, Ombitasvir, Pibrentasvir, Velpatasvir

HCV NS5B (Polymerase) Inhibitors

• Dasabuvir, Sofosbuvir

HCV Protease Inhibitors

• Asunaprevir, Boceprevir, Glecaprevir, Grazoprevir, Paritaprevir, Simeprevir, Telaprevir, Voxilaprevir

Combination Therapies

• Epclusa, Harvoni, Mavyret, Technive, Viekira Pak, Vosevi, Zepatier

• Dailymed label info on Simeprevir
• FDA Simeprevir

Simeprevir Resources
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