Back HCV Treatment CROI 2012: GS-7977 Rapidly Suppresses HCV, but Most Patients Relapse after Stopping Treatment

CROI 2012: GS-7977 Rapidly Suppresses HCV, but Most Patients Relapse after Stopping Treatment


An interferon-free combination of the experimental polymerase inhibitor GS-7977 plus ribavirin potently and rapidly reduced hepatitis C virus (HCV) levels, but almost all patients experienced viral rebound after they stopped treatment, researchers reported Tuesday at the 19th Conference on Retroviruses and Opportunistic Infections (CROI 2012) this week in Seattle.

Approval of the first direct-acting agents for hepatitis C has ushered in a new era of treatment, but many patients and clinicians eagerly await therapy that does not require interferon and its difficult side effects.

GS-7977 (renamed from PSI-7977 after Gilead Sciences acquired Pharmasset late last year) is a uridine nucleotide analogue HCV polymerase inhibitor that has demonstrated potent antiviral activity, good safety, and a high barrier to resistance in early studies. In contrast with the 2 currently approved HCV protease inhibitors, GS-7977 can be taken once-daily with no food requirements.

Edward Gane from Auckland City Hospital in New Zealand presented the latest data from the ELECTRON trial. As reported at the AASLD Liver Meeting last fall, 100% of previously untreated patients with easier-to-treat HCV genotypes 2 or 3 experienced rapid virological response (RVR) using a dual combination of GS-7977 plus ribavirin for 12 weeks. All went on to achieve sustained virological response (SVR) at 12 and 24 weeks after the end of treatment, generally regarded as a cure.

Following these promising results, ELECTRON investigators added new study arms to see if people with more difficult-to-treat HCV genotype 1 -- both treatment-naive and prior null responders -- might see similar benefits.

This analysis included 10 genotype 1 null responders who previously had less than a 2 log reduction in HCV RNA with a prior course of pegylated interferon plus ribavirin. All were treated with 400 mg once-daily GS-7977 plus 1000 or 1200 mg weight-based ribavirin for 12 weeks.

A majority of participants (65%) were men, 90% were white, and the average age was 48 years. Most had HCV genotype 1a; 20% of prior null responders and 44% of treatment-naive patients had the favorable IL28B CC gene pattern.

Data from genotype 1 null responders were presented at CROI. Data for genotype 1 treatment-naive patients will be presented at the EASL meeting next month.


  • Both treatment-naive people and null responders experienced rapid viral suppression, with all of them reaching undetectable HCV RNA (< 15 IU/mL) by week 4, as was seen previously in the genotype 2/3 group.
  • All genotype 1 participants maintained viral suppression at the end of 12 weeks of therapy. 
  • Among genotype 1 null responders followed past the end of treatment, however, results began to diverge from those of the genotype 2/3 patients.
  • All but 1 null responder experienced viral relapse soon after stopping therapy.
  • The sole sustained responder had a highly favorable profile of response predictors -- a young woman with the IL28B CC pattern and minimal liver fibrosis.
  • GS-7977/ribavirin continued to show good tolerability.
  • There were no serious adverse events and no premature discontinuations.
  • No viral breakthrough occurred while on treatment, confirming the drug's high barrier to resistance.

Based on these findings, the researchers suggested that future studies of GS-7977 for genotype 1 prior null responders will likely require longer treatment duration or addition of another direct-acting antiviral agent.

Speaking at an accompanying press conference, Douglas Dieterich from Johns Hopkins suggested that, "as far as patients are concerned, duration doesn’t matter," as long as it’s a well-tolerated pill and not interferon.

"Interferon-free treatment is not a dream", Gane concluded. "It's a reality and I think it will be here within the next 5 years."



E Gane, C Stedman, J Anderson, et al. 100% Rapid Virologic Response for PSI-7977 + Ribavirin in Genotype 1 Null Responders (ELECTRON): Early Viral Decline Similar to that Observed in Genotype 1 and Genotype 2/3 Treatment-naive Patients. 19th Conference on Retroviruses and Opportunistic Infections (CROI 2012). Seattle, WA. March 5-8, 2012. Abstract 54LB.