Back HCV Treatment EASL 2012: Telaprevir 100% Effective for IL28B CC, Adding VX-222 Overcomes Unfavorable Genes

EASL 2012: Telaprevir 100% Effective for IL28B CC, Adding VX-222 Overcomes Unfavorable Genes


Adding telaprevir (Incivek) to pegylated interferon and ribavirin cured all hepatitis C patients with the favorable IL28B gene pattern, researchers reported at the 47th International Liver Congress (EASL 2012) last month in Barcelona. Another study found that adding the experimental HCV polymerase inhibitor VX-222 raised cure rates even for those with unfavorable IL28B patterns.

The advent of direct acting antiviral agents has ushered in a new era of treatment for chronic hepatitis C. The first 2 approved agents -- the hepatitis C virus (HCV) protease inhibitors telaprevir and boceprevir (Victrelis) -- used with pegylated interferon/ribavirin improve sustained virological response (SVR) rates and shorten treatment duration for many patients, but several agents in the development pipeline appear more potent.

Jean-Pierre Bronowicki from INSERM Nancy and colleagues retrospectively analyzed patient characteristics and cure rates in the pivotal PROVE2 trial, looking specifically at IL28B gene patterns.

The IL28B gene plays a role in response to interferon. People who carry the rs12979860 CC gene pattern are more likely to spontaneously clear HCV and respond better to interferon-based treatment, those with the TT pattern have the worst outcomes, and those with the CT pattern are in between.

The researchers looked at SVR rates among 141 treatment-naive, HCV genotype 1, CC and non-CC patients in the PROVE2 trial in Europe who received 12 weeks of triple combination therapy with telaprevir plus pegylated interferon alfa-2a (Pegasys) and ribavirin.

About two-thirds of analyzed participants were men and the average age was about 45 years. Half had HCV subtype 1b and most had mild (53%) or moderate (27%) fibrosis. Looking at IL28B gene patterns, 30% were CC, 59% were CT, and 11% were TT.


  • 100% of CC patients achieved SVR with 12 weeks of triple therapy, compared with 44% of CT patients and 20% of TT patients.
  • CC patients also had substantially higher SVR rates than CT or TT patients using other randomized treatment regimens or standard therapy:
    • Telaprevir 12 weeks + pegylated interferon/ribavirin 24 weeks: 94%, 67%, and 33%, respectively;
    • Telaprevir + pegylated interferon dual therapy for 12 weeks: 75%, 18%, and 0%, respectively;
    • Pegylated ribavirin /ribavirin alone for 48 weeks: 64%, 31%, 25%.

"These results suggest that 12 weeks of the triple combination of telaprevir, peginterferon, and ribavirin are sufficient to cure IL28B CC treatment-naive patients infected with HCV genotype 1 without cirrhosis," the researchers concluded.

Vertex Pharmaceuticals is now conducting an ongoing Phase 3b study to evaluate a total triple therapy treatment duration as short as 12 weeks for people with IL28B CC.


Marina Penney from Vertex presented findings from the Phase 2a ZENITH trial, an ongoing study assessing the safety, tolerability, and antiviral activity of the next generation HCV polymerase inhibitor VX-222 for previously untreated genotype 1 patients.

The study randomly assigned participants to receive VX-222/telaprevir dual therapy, VX-222/telaprevir/ribavirin triple therapy, or VX-222/telaprevir/pegylated interferon/ribavirin quadruple therapy.

The current analysis looked at 59 patients who received 12 weeks of either 100 mg or 400 mg VX-222 in a quadruple regimen. Those who had undetectable HCV RNA at weeks 2 and 8 were eligible to stop all treatment at week 12. Here, about one-third had the IL28B CC pattern, 46% were CT, and 20% were TT.


  • At Week 2, people with the CC pattern were substantially more likely than those with CT or TT patterns to achieve undetectable HCV RNA (67%, 18%, and 17%, respectively, in the 100 mg VX-222 arm; 75%, 56%, and 33%, respectively, in the 400 mg arm).
  • By week 4, however, proportions of patients with undetectable HCV viral load were statistically similar regardless of IL28B gene patterns (92%, 64%, and 100%, respectively, in the 100 mg VX-222 arm; 88%, 94%, and 83%, respectively, in the 400 mg arm).
  • At week 12, 67% of CC patients in the 200 mg arm and 75% in the 400 mg arm were eligible to stop treatment, compared with 38% and 50%, respectively, overall.

"There was an association between IL28B genotype and undetectable HCV RNA at week 2 in [VX-222 200 mg and 400 mg arms], however this association disappears by week 4 due to high RVR rates across all IL28B genotypes," the researchers concluded.

"Patients from all IL28B genotypes achieved high SVR rates, thus IL28B may not be predictive of response to [quadruple] therapy in treatment-naive patients with genotype 1 chronic HCV," they added.

Vertex announced that it will soon open a Phase 2b study to evaluate an all-oral, interferon-free regimen as short as 12 weeks in people with genotype 1a and 1b.



JP Bronowicki, C Hezode, L Bengtsson, et al. 100% SVR in IL28B CC Patients Treated with 12 Weeks of Telaprevir, Peginterferon and Ribavirin in the PROVE2 Trial. 47th International Liver Congress (EASL 2012). Barcelona, April 18-22, 2012. Abstract 1094.

M Penney, C De Souza, S Seepersaud, et al. All IL28B Genotypes Have High SVR Rates in Patients Treated with VX-222 in Combination with Telaprevir/Peginterferon/Ribavirin in the ZENITH Study. 47th International Liver Congress (EASL 2012). Barcelona, April 18-22, 2012. Abstract 1203.

Other Source

Vertex Pharmaceuticals. Vertex Advances Incivek (telaprevir) and Broad Portfolio of Medicines in Development With Goal of Further Expanding and Improving Treatment for People With Hepatitis C. Press release. April 18, 2012.