April 22, 2012

EASL 2012: [SLIDES] Once Daily GS-7977 Plus Ribavirin in HCV Genotypes 1-3: The ELECTRON Trial

Gilead Sciences, Inc.
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Foster City, CA 94404
Tel: (650)522-5373
Fax: (650)522-5260

Poster
Number 1113

47th Annual Meeting of the
European Association for the Study of the Liver
April 18 - 22, 2012
Barcelona, Spain

E. Gane1, C. Stedman2, R. Hyland3, R. Sorensen3, W. Symonds3, R. Hindes3, M. Berrey

1New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, 2Gastroenterology Department, Christchurch Hospital, Christchurch, New Zealand; 3Gilead Sciences, Foster City, CA

Introduction

  • GS-7977 (formerly PSI-7977) is a potent, specifi c nucleotide analog developed
    for the treatment of patients chronically infected with hepatitis C virus (HCV)
  • Safe and well tolerated in clinical studies
  • Once daily, with or without food
  • Potent antiviral activity
  • High barrier to resistance

─ No virologic breakthrough to date

  • We conducted a Phase 2 trial (ELECTRON) to evaluate the safety and effi cacy
    of GS-7977 and ribavirin (RBV) with and without pegylated interferon (PEG) in
    genotype (GT) 1-3 patients with chronic HCV infection
  • Results from the fi rst 5 arms of ELECTRON using interferon-sparing/-free
    regimens in patients with HCV GT 2/3 and GT 1 prior null responders:1,2,3,4

─ SAFETY

  • GS-7977 400 mg QD + RBV for 12 weeks was well tolerated with no
    attributable safety signal

─ POTENCY

  • GS-7977 + RBV elicited rapid suppression of HCV RNA → 100% RVR
  • All GT 2/3 treated with GS-7977 + RBV patients achieved SVR24
  • Patients treated with GS-7977 monotherapy achieved 60% SVR24
  • GT 1 prior null responders achieved 11% SVR4 with a 12-week GS-7977+
    RBV regimen
  • No virologic breakthrough has been observed during treatment with
    GS-7977

Objective

To evaluate the safety and effi cacy of GS-7977 400 mg once daily in combination
with RBV with and without PEG in the following populations:

  • Treatment-naïve GT 2/3 patients treated with GS-7977 + RBV + PEG for
    8 weeks
  • Prior null responder GT 1 patients treated for 12 weeks with GS-7977 + RBV
  • Treatment-naïve GT 1 patients treated for 12 weeks with GS-7977 + RBV
  • Previously treated GT 2/3 patients treated for 12 weeks with GS-7977 + RBV

Methods

Figure 1. ELECTRON Study Design

Fig1

  • Null responders were defi ned as patients with <2 log10 IU/mL decline from
    baseline HCV RNA after at least 12 weeks of PEG and RBV
  • Treatment-experienced patients were defi ned as those who had any of the
    following responses after at least 12 weeks of PEG and RBV:
    • <2 log10 IU/mL decline from baseline in HCV RNA
    • ≥2 log10 IU/mL reduction in HCV RNA, but HCV RNA >LOQ at end of
    treatment
    • HCV RNA <LOQ at end of treatment, but subsequent HCV RNA >LOQ
    (relapsers)

Results

Table 1. Baseline Patient & Disease Characteristics

Table1

Figure 2. On-treatment Viral Suppression

Fig2

Table 2. Patients with HCV RNA <LOD Over Time, n/N (%)

Table2

*1 subject relapsed at the SVR8 time point after having previously achieved SVR4

Table 3. Safety and Tolerability

Table3

*SAEs considered unrelated to GS-7977
†In >1 patient treated with GS-7977; no Grade 3 or 4 AEs occurred in treatment arms lacking PEG

Resistance Data:

  • Population sequencing has been completed in 5 of 8 relapsers from the GT-1
    prior null responder arm: no S282T was found
  • Deep sequencing did not identify any S282T-containing mutants

Table 4. Grade 3 or 4 Laboratory Abnormalities in >1 Patient

Table4

Conclusions

  • 88% of treatment-naïve GT 1 patients achieved SVR4 following 12 weeks of therapy with GS-7977 + RBV
    ─ This result suggests that 12 weeks of GS-7977 + RBV can potentially provide higher rates of SVR in treatment-naïve GT 1 patients than those achieved with longer durations of PI + PEG/RBV
  • The combination of GS-7977 + RBV was well tolerated in all genotypes regardless of prior treatment history
  • No virologic breakthrough occurred in any arm, suggesting a high barrier to resistance
    ─ To date, the S282T mutation has not been seen in any GS-7977/RBV regimen
  • These results where GS-7977 400 mg once daily (QD) is being utilized in a variety of regimens and populations further demonstrate the utility of GS-7977 across a broad spectrum of HCV disease treatment

References and Acknowledgements

1. Lawitz E, et al. J Hepatol 2011;54:S543.
2. Gane E, et al. AASLD 2011
3. Gane E, et al. APASL 2012
4. Gane E, et al. CROI 2012

Thanks to all the patients and their families and:
• Christian Schwabe, Vithika Suri, ACS
• Catherine Stedman, Richard Robson, CCS

© 2012 Gilead Sciences

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