TreatmentUpdate
202

March/April 2014 

Simeprevir + interferon + ribavirin in HCV genotype 4 infection

HCV genotype 4 (GT4) is relatively common in the Middle East and Africa. Due to migration, travel and tourism, the number of people with GT4 is increasing in high-income countries.

Simeprevir has antiviral activity against HCV GT1 and has been licensed for treating this strain. Researchers have recently tested it as part of combination therapy in people with GT4, who were either new to HCV therapy or who had previously used peginterferon but without success.

Study details

Stopping rules – Doctors stopped therapy if blood tests confirmed a poor virologic response at any of the following points during the course of the study:

  • Week 4 – HCV viral load was greater than 1,000 IU/ml
  • Week 12 – HCV viral load was greater than 1,000 IU/ml
  • Week 24 – HCV viral load was 25 IU/ml or greater
  • Week 36 – HCV viral load was 25 IU/ml or greater

Participants were divided into two groups and assigned to receive the following regimens:

Group 1 – People who were new to HCV treatment or who had previously been treated with an initially favourable response but then relapsed:

  • Simeprevir 150 mg once daily (for 12 weeks) + peginterferon + ribavirin; at week 24 if HCV RNA was less than 25 IU/ml, therapy stopped. If HCV RNA was greater than this amount, therapy with peginterferon and ribavirin continued for 24 more weeks.

Group 2 – People who had a prior poor response to HCV therapy:

  • Simeprevir 150 mg once daily (for 12 weeks) + peginterferon + ribavirin (for a total of 48 weeks)

For this interim analysis, researchers analysed data from 107 participants distributed as follows:

  • 35 participants who had not been treated previously
  • 72 participants who were treatment experienced

Treatment-experienced participants could be further subdivided as follows:

  • prior relapsers – 22 people
  • prior partial responders – 10 people
  • prior null responders – 40 people

The average profile of participants was as follows:

  • 79% men, 21% women
  • age – 50 years
  • 72% were white, 28% were black
  • HCV viral load – 6.1 log
  • main subtypes of HCV GT4 were 4a and 4d; other subtypes included c, e, f, h, k, o, q, r
  • most participants had a mild-to-moderate degree of liver damage

Results – Week 4

Having HCV that was less than 25 IU/ml at week 4 is called a rapid virologic response (RVR) and this occurred as follows:

  • Overall – 66%
  • never previously used treatment – 80%
  • prior relapsers – 90%
  • prior partial responders – 40%
  • prior null responders – 49%

As this is an interirm analysis, not all the participants had completed the study when the data were analysed. However, out of all 30 participants who completed 24 weeks of therapy, 29 (97%) had a viral load less than 25 IU/ml.

Side effects

Most side effects were generally of mild-to-moderate intensity. Since all participants received interferon and ribavirin, side effects were common. However, only four participants had side effects that were considered serious by researchers and only one participant quit simeprevir because of side effects. No one died while in the study.

Common side effects in the first 12 weeks of the study (when simeprevir was used) were as follows:

  • anemia – 8% (generally mild)
  • less-than-normal levels of neutrophils – 5% (mostly mild-to-moderate)
  • itchy skin – 19%
  • rash – 13%
  • higher-than-normal levels of bilirubin in the blood (2%)

Not enough patients have completed the study to draw firm conclusions about the effectiveness of this therapy. However, the interim results are very promising.

—Sean R. Hosein

REFERENCE

Moreno C, Hezode C, Marcellin P, et al. Simeprevir wth peginterferon and ribavirin in treatment-naïve or experienced patients with chronic HCV genotype 4 infection: interim results of a phase II trial. In: Program and abstracts of the 14th European AIDS Conference, 16-19 October 2013, Brussels, Belgium. Abstract LBPS9/6.