Simeprevir

Simeprevir

File:Simeprevir.svg
Clinical data
Trade names	Olysio
Synonyms	TMC435; TMC435350
Legal status
Legal status	US: ℞-only
Identifiers
CAS Number	923604-59-5
PubChem CID	56928193
ChemSpider	23331536
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C38H47N5O7S2
Molar mass	749.94 g/mol
3D model (JSmol)	Interactive image
SMILES Cc1c(ccc2c1nc(cc2O[C@@H]3C[C@@H]4[C@@H](C3)C(=O)N(CCCC/C=C\[C@@H]5C[C@]5(NC4=O)C(=O)NS(=O)(=O)C6CC6)C)c7nc(cs7)C(C)C)OC
InChI InChI=1S/C38H47N5O7S2/c1-21(2)30-20-51-35(40-30)29-18-32(26-13-14-31(49-5)22(3)33(26)39-29)50-24-16-27-28(17-24)36(45)43(4)15-9-7-6-8-10-23-19-38(23,41-34(27)44)37(46)42-52(47,48)25-11-12-25/h8,10,13-14,18,20-21,23-25,27-28H,6-7,9,11-12,15-17,19H2,1-5H3,(H,41,44)(H,42,46)/b10-8-/t23-,24-,27-,28-,38-/m1/s1 Key:JTZZSQYMACOLNN-VDWJNHBNSA-N

Simeprevir (formerly TMC435; trade name Olysio) is a drug for the treatment and cure of hepatitis C. It was developed by Medivir and Johnson & Johnson's pharmaceutical division Janssen Pharmaceutica. In the United States, simeprevir is approved by the Food and Drug Administration for use in combination with peginterferon-alfa and ribavirin. Simeprevir has been approved in Japan for the treatment of chronic hepatitis C infection, genotype 1.

Mechanism of action

Simeprevir is a hepatitis C virus protease inhibitor.

Simeprevir is a NS3/4A protease inhibitor, thus preventing viral maturation through inhibition of protein synthesis. Simeprevir is administered as one capsule once daily with pegylated interferon and ribavirin for the treatment of genotype 1 or genotype 4 chronic hepatitis C in adult patients with compensated liver disease (including cirrhosis), with or without HIV-1 co-infection, who are treatment naive or who have failed previous interferon therapy. Genotype 1 is the most prevalent form of hepatitis C virus (HCV) worldwide.

Clinical study

Simeprevir has been tested in combination regimens with pegylated interferon alfa-2a and ribavirin, and in interferon-free regimens with other direct-acting antiviral agents including daclatasvir and sofosbuvir

Results from three phase 3 randomized, double-blind, placebo controlled clinical trials (C208, C216, and HPC3007) in patients with chronic HCV GT1 were favourable and resulted in FDA supporting the approval of Simeprevir for Hepatitis C genotype 1. Interestingly, members of the FDA commented following a presentation by Johnson & Johnson (24 October 2013) that post-marketing studies in racial and ethnic minorities, patients co-infected with HIV, and other underrepresented populations is needed.

In the pooled analysis, 2% of those in the simeprevir group had serious adverse events, versus 3% of those in the control group during the initial 12 weeks. A total of 3 patients (0.4%) in the simeprevir group had significant adverse events, which were determined to be related to simeprevir by the study investigator; 1 patient experienced major depression and 2 patients experienced photosensitivity reactions. A total of 4 deaths occurred in the treatment groups, and they were judged to be unrelated to treatment. Other common adverse events were rash (218 [28%] treatment groups; 79 [20%] control groups), influenza like illness (203 [26%] treatment groups; 84 [21%] control groups), pruritis (168 [22%] treatment groups; 58 [15%] control groups), and nausea (173 [22%] treatment groups; 70 [18%] control groups). For all (new) medications, adverse events or suspected adverse events should be made known to a relevant medical practitioner and health professionals are advised to report this to local authorities to promote surveillance and potential recognition of these negative effects.