April 22, 2012

Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Tel: (650)522-6009
Fax: (650)522-5260

Poster
Number 1421

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

M. Sulkowski1, M. Rodriguez-Torres2, E. Lawitz3, M. Shiffman4, S. Pol5, R. Herring6, J.G. McHutchison7, P.S. Pang7, K.A. Wong7, B. Massetto7, Y. Zhu7, D.M. Brainard7, D. Wyles8, F. Habersetzer9

1Johns Hopkins University School of Medicine, Lutherville, MD; 2Fundacion de Investigacion de Diego, Santurce, PR; 3Alamo Medical Research, San Antonio, TX; 4Liver Institute of Virginia, Richmond, VA; 5Hôpital Necker, Paris, France; 6Nashville Gastrointestinal Specialists, Inc.,
Nashville, TN; 7Gilead Sciences, Inc., Foster City, CA; 8University of California, San Diego, La Jolla, CA; 9Hôpitaux Universitaires de Strasbourg, Strasbourg, France

Introduction

  • Combinations of direct-acting antivirals (DAAs) without interferon (IFN) have demonstrated variable rates of sustained virologic response (SVR) in genotype 1 patients1,2
    ─ Lower SVR rates have been reported in genotype 1a as compared to genotype 1b HCV
    ─ The optimal duration of IFN-free treatment regimens in genotype 1 has not been established
    ─ Virologic failure in IFN-free regimens without a nucleos(t)ide analogue has been associated with multidrug resistance
  • This ongoing Phase 2 study (NCT01353248) was designed to assess the effi cacy and safety of a 3-DAA-containing regimen plus ribavirin (RBV), including a protease inhibitor, NS5A inhibitor, and a non-nucleoside NS5B inhibitor
  • We report preliminary SVR4, SVR12, and safety data from patients treated for 12 or 24 weeks

Table 1. In Vitro Characteristics of DAAs Administered in the Current Study

Tab1

*In vitro and following 3 or 7 days of monotherapy in HCV-infected patients

Methods

Patients

Major inclusion criteria:

  • Chronic infection with HCV genotype 1a or 1b
  • HCV treatment-naïve
  • Plasma HCV RNA ≥104 IU/mL during screening
  • Exclusion of cirrhosis by liver biopsy within 2 years or Fibroscan within 6 months

Major exclusion criteria:

  • Coinfection with human immunodefi ciency virus or hepatitis B virus
  • Contraindication to treatment with IFN and/or RBV
  • Current or prior hepatic decompensation
  • Prespecifi ed laboratory abnormalities

Study design (Figure 1)

  • Patients were randomized 1:2 to the following treatment groups:
    ─ Arm 1: GS-5885 30 mg QD + GS-9451 200 mg QD + GS-9190 30 mg BID + RBV
    ─ Arm 2: GS-5885 90 mg QD + GS-9451 200 mg QD + GS-9190 30 mg BID + RBV
  • Patients with HCV RNA ≥25 IU/mL at Week 2 (non-vRVR) were offered peginterferon (PEG)-containing rescue therapy or discontinuation from the study
  • Patients in Arm 2 with HCV RNA <25 IU/mL from Week 2 through Week 10 were
    re-randomized at Week 12 to either stop treatment or continue treatment through Week 24

Figure 1. Study Design  Fig1

  • Randomization stratifi ed by HCV RNA at screening (≤ or >800,000 IU/mL) and genotype 1a or 1b
  • Virologic breakthrough defi ned as confi rmed, on-treatment HCV RNA ≥25 IU/mL after Week 2
    ─ Patients with breakthrough offered PEG-containing rescue therapy
  • Plasma HCV RNA measured using the Roche COBAS TaqMan HCV/HPS assay v2.0 with a lower limit of quantifi cation of 25 IU/mL

Table 2. Summary of Baseline Characteristics (N = 140)

Tab2

Figure 2. Patient Disposition

Fig2

Table 3. Preliminary Post-treatment Response Rates by Treatment Arm and
Genotype Subtype, n (%)

Tab3

*SVR4 and SVR12 rates calculated using treatment completers who had available data at the given timepoint

Figure 3. On-treatment Response by Arm, IL28B Genotype, and HCV Subtype

Fig3

Figure 4. HCV RNA Kinetics in Patients with Virologic Breakthrough by Treatment Arm and Genotype Subtype

Fig4

45 patients enrolled in rescue Rescue therapy with PEG + GS-5885 + GS-9451

Table 4. Patients Achieving HCV RNA <25 IU/mL During Rescue Therapy

Tab4

a. 1 early termination (ET) due to lack of effi cacy; 1 ET due to an AE
b. ET due to lack of effi cacy; 1 of 16 patients experienced breakthrough after achieving <25 IU/mL
c. 1 ET due to lack of effi cacy; 1 ET due to an AE; 1 patient has not reached <25 IU/mL after 16 weeks in rescue

Table 5. Safety Summary, n (%)

Tab5

  • One subject in Arm 1 had 2 SAEs (pancreatitis requiring overnight hospitalization and viral gastroenterititis); no doses of study medications were missed
  • Two subjects in Arm 2 had 5 AEs (acute psychosis, alcohol intoxication, decreased muscle mass, heartburn, irritability)
  • Reported grade 3 AEs were pancreatitis (also SAE), stomatitis, fatigue, elevated bilirubin, viral gastroenteritis (also SAE), alcohol poisoning (led to study discontinuation), tendonitis, and acute psychosis

Table 6. Most Common (≥10%) Treatment-Emergent AEs, n (%) Arm 1 (GS-5885 30 mg) Arm 2

Tab6

Table 7. Laboratory Parameters of Interest, n (%)

Tab7

  • Rates and severity of anemia were consistent with what has been reported in other IFN-free, RBV-containing studies3,4
  • Indirect hyperbilirubinemia was observed in approximately 60% of patients without concomitant transaminase elevations
    ─ GS-9451 is an inhibitor of the bilirubin transporter protein OATP1B1 and has been associated with transient indirect hyperbilirubinemia in healthy volunteers5
    ─ No Grade 4 (≥6.0 g/dL) hyperbilirubinemia was observed

Summary and Conclusions

Preliminary data from this ongoing Phase 2 study of a multi-DAA
regimen without a nucleos(t)ide analogue has shown in genotype 1
patients that:

  • A regimen including 3 DAAs + RBV was well tolerated for up to 24 weeks
  • The 90-mg dose of GS-5885 provides improved antiviral effi cacy over the 30-mg dose of GS-5885 without an increase in toxicity
  • Rates of viral breakthrough and relapse were lower in genotype 1b patients than in genotype 1a patients
  • Patients with the IL28B CC genotype showed lower rates of breakthrough than IL28B non-CC patients, particularly in Arm 2 (GS-5885 90mg)
  • Virologic breakthrough was associated with multi-DAA resistance
    ─ Viral suppression with the addition of PEG occurs in most virologic failures

References and Acknowledgements

1. Lok A, et al. N Engl J Med 2012;366;3:216-24.
2. Zeuzem S, et al. Gastroenterology 2011;141:2047-54.
3. Zeuzem et al. AASLD 2011. Abstract LB-15
4. Gane EJ, et al. AASLD 2011. Abstract 34
5. Yang JC, et al. EASL 2012.

The study team and investigators thank the patients for their participation in this clinical trial.

© 2012 Gilead Sciences, Inc.

Source

E.J. Gane,1 P. Pockros,2 S. Zeuzem,3 P. Marcellin,4 A. Shikhman,5 C. Bernaards,6 E. Yetzer,6 N.S. Shulman,6 X. Tong,5 I. Nájera,5 A. Bertasso,5 J. Hammond,5 S. Stancic5

1Auckland Clinical Studies, Auckland, New Zealand; 2Scripps Clinic and Scripps Translational Science Institute, La Jolla, CA, USA; 3J. W. Goethe University Hospital, Theodor-Stern-Kai, Frankfurt, Germany; 4Hôpital Beaujon, Clichy, France; 5Roche, Nutley, NJ, USA;
6Genentech, South San Francisco, CA, USA

INTRODUCTION

  • The hepatitis C treatment landscape is rapidly evolving. The recent regulatory approval of first-generation protease inhibitors has resulted in a new standard of care for genotype 1 patients, consisting of peginterferon alfa/ribavirin (RBV) in combination with telaprevir or boceprevir, with sustained virological response (SVR) rates of 68–75% achievable in treatment naive patients.[1-3]
  • However, safety and tolerability remain suboptimal. The benefits of adding one direct-acting antiviral agent (DAA) to peginterferon alfa/RBV remain limited due to the underlying safety and tolerability issues associated with interferon-based treatment.
  • An all-oral, interferon-free DAA combination treatment would fill an unmet medical need and potentially further change the treatment paradigm.[4]
  • Two DAAs currently in phase II clinical development are mericitabine (MCB) and danoprevir (DNV; RG7227).
  • MCB is a selective and non-cytotoxic hepatitis C virus (HCV) polymerase inhibitor which is active against all HCV genotypes and has a high barrier to resistance.[5-7]
  • DNV is a potent, macrocyclic, HCV protease inhibitor that has equipotent activity against HCV genotypes 1, 4 and 6 in vitro.[8,9]
  • The phase I INFORM-1 study demonstrated that treatment with a combination of these two DAAs for 13 days resulted in significant reductions in HCV RNA in both treatment-naive and prior null responders and was well tolerated.[4]
  • Co-administration of ritonavir with lower doses of DNV has since been shown to decrease the overall exposure of DNV while maintaining potent antiviral activity.[10]
  • The phase IIb INFORM-SVR study is investigating the safety and efficacy of response-guided treatment with MCB in combination with ritonavir-boosted DNV (DNVr) with and without RBV for 12 or 24 weeks in treatment naive patients with genotype (G) 1 chronic HCV infection.
  • Here, results from a 12-week post-treatment interim analysis of the INFORM-SVR study are presented.
  • METHODS

  • INFORM-SVR is an ongoing, randomised, multicentre, double blind, parallel group phase IIb study. Eligible patients are treatment-naive, chronic HCV G1-infected adults (≥18 years of age) with F0–F2 fibrosis.
  • Patients were randomised (1:1) to receive a combination of MCB (1000 mg bid) and DNVr (100 mg/100 mg bid) plus either RBV (1000/1200 mg daily) (Arm A) or placebo (Arm B) for 12 or 24 weeks (Figure 1).
  • In both arms, patients achieving an early extended rapid virological response (eRVR2, defined as unquantifiable HCV RNA [<43 IU/mL]) between week 2 to week 8, and with undetectable HCV RNA [<15 IU/mL] at week 10, were re-randomised (1:1) at week 12 to either discontinue treatment (total therapy duration: 12 weeks) or continue the assigned regimen until week 24 (total therapy duration: 24 weeks).
  • HCV RNA was measured using Roche COBAS® AmpliPrep/ COBAS TaqMan® HCV Test with a lower limit of detection of 15 IU/mL and a lower limit of quantification of 43 IU/mL.
  • The primary outcome of the trial was SVR24.
  • Resistance monitoring was performed in patients who experienced breakthrough, partial response, non-response or relapse through sequencing (population and clonal) of target genes.

Figure 1: INFORM-SVR study design

Fig1

Arm A (12 week option) and Arm B (both 12 and 24 week options) stopped prematurely at different times due to unexpectedly high relapse rates. eRVR2: extended rapid virologic response; HCV RNA unquantifiable (<43 IU/mL) between week 2 and 8 and undetectable (<15 IU/ml) at week 10. Continue if HCV RNA quantifiable between week 2 and week 8 (≥43 IU/mL) but <43 IU/mL at week 10, or, HCV RNA <43 IU/mL between week 2 and 8 and <43 IU/mL but ≥15 IU/mL at week 10. Patients with virologic failure (confirmed rebound or <2 log drop after 1 month of treatment) discontinued treatment. Patients with quantifiable virus at week 10 stopped treatment at week 12.

RESULTS

Patients

  • A total of 169 patients were randomised to treatment (Arm A n=83; Arm B n=86) and received at least one dose of study medication.
  • Demographics were balanced between arms (Table 1).

Table 1: Baseline characteristics of the study population

Tab1

ALT = alanine aminotransferase; BMI = body mass index; DNVr = ritonavir-boosted danoprevir; MCB = mericitabine; RBV = ribavirin.

  • Randomisation to 12 weeks of treatment in Arm A and to the whole of Arm B was stopped prematurely due to high relapse rates, and patients in Arm B were offered follow-on with peginterferon alfa-2a (40KD)/RBV therapy.
  • As a result, only 20/169 patients were randomised to 12 weeks of treatment (Arm A n=17; Arm B n=3) and thus, for efficacy analyses, Arm A (24 weeks of treatment), is the key group analysed here (n=66).

Efficacy

  • Among patients randomised to Arm A for 24 weeks (n=66), two patients were excluded from the present efficacy analysis; one patient discontinued for reasons other than virological breakthrough or an adverse event (AE) and one patient was lost to follow-up.
  • The efficacy population thus consisted of 64 patients who received MCB combined with DNVr and RBV for 24 weeks; 43 patients with HCV G1a and 21 with HCV G1b.
  • SVR12 rates for G1a and G1b patients receiving 24 weeks of MCB plus DNVr and RBV treatment are presented in Figure 2.
    ——O verall, 41% of patients achieved SVR12 (26/64; 95% CI 28–53). However, SVR12 rates were considerably higher among patients with HCV G1b (71%; 95% CI 50–92) compared with patients with G1a infection (26%; 95% CI 12–39)
    ——W hen SVR12 rates were stratified according to IL28B genotype (CC and non-CC), 32% of patients with IL28B CC genotype, and 44% with non-CC genotype achieved SVR12
    —— I n G1a patients, SVR12 rates were similar irrespective of IL28B genotype. However, in G1b patients the number of IL28B CC patients was too small (n=4) to allow a meaningful comparison to patients with IL28B non-CC genotype.
  • Among patients in Arm A treated with MCB combined with DNVr and RBV for 24 weeks, 60.5% (26/43) of HCV G1a-infected patients achieved an eRVR2 compared to 47.6% (10/21) of patients with HCV G1b infection.
  • Among the patients achieving an eRVR2, 31% (8/26) of G1a and 80% (8/10) G1b achieved an SVR (Figure 3).

Figure 2: SVR12 rates in patients receiving 24 weeks MCB + DNVr + RBV
(Arm A) by HCV genotype and IL28B genotype

Fig2

G = HCV genotype; DNVr = ritonavir-boosted danoprevir; MCB = mericitabine; RBV = ribavirin; SVR12 = sustained virological response after 12 weeks of untreated follow-up

Figure 3: SVR12 rates according to eRVR2 status and HCV genotype in patients randomised to MCB + DNVr + RBV for 24 weeks (Arm A)

Fig3

G = HCV genotype; DNVr = ritonavir-boosted danoprevir; eRVR = extended rapid virological response; MCB = mericitabine; RBV = ribavirin; SVR12 = sustained virological response after 12 weeks of untreated follow-up.

Breakthrough rates

  • In total, among all patients who received at least one dose of study medication, 26 patients experienced breakthrough: 8 in Arm A (8/83; 9.6%) and 18 in Arm B (18/86; 20.9%).
  • When evaluated by HCV genotype, breakthrough rates were higher among HCV G1a patients (Arm A: 6/56; 11%; Arm B: 15/57; 26%) compared to G1b patients (Arm A: 2/27; 7%; Arm B: 3/29; 10%).
  • DNV resistance mutations were detected by population sequencing in 25 patients at virological breakthrough; sequencing could not be performed in one G1a patient due to low viral load.
    ——The NS3 R155K amino acid change was the only known DNV resistance mutation detected at the population level in 16 patients (14 G1a, two G1b)
    ——R155K + V36M/A was observed in five G1a patients
    ——D168T was observed in one G1b patient
    ——D168E + V36V/G was observed in one G1b patient
    ——One patient (GT1a) had a dual resistant virus to MCB and DNV, bearing substitutions NS5B S282T and NS3 R155K
    ——R155K/Q was observed in one G1b-infected patient
  • The dual resistant virus reverted to wild type by week 12 of follow-up (T282S at week 8 and K155R at week 12); clonal sequencing and/or ultra-deep pyrosequencing analyses are ongoing.

Safety

  • Treatment with MCB in combination with DNVr and RBV was safe and well tolerated and no safety concerns were identified (Tables 2 and 3).
  • No serious AEs were reported during treatment in Arm A.
  • No Grade 4 laboratory abnormalities were reported (Table 2).

Table 2: Adverse events and laboratory abnormalities

Tab2

AE = adverse event; ALT = alanine aminotransferase; ANC = absolute neutrophil count;
AST = aspartate aminotransferase; DNVr = ritonavir-boosted danoprevir; MCB = mericitabine;
RBV = ribavirin.
* SAE due to multiple myeloma at 63 days after last dose
† discontinuation was due to oropharyngeal discomfort

Table 3. Most common adverse events (≥10%)*

Tab3

DNVr = ritonavir-boosted danoprevir; MCB = mericitabine; RBV = ribavirin.
* Includes mild, moderate and severe AEs

CONCLUSIONS

  • In G1b patients, 24 weeks of MCB in combination with DNVr and RBV yielded an  SVR12 rate of 71%, while in G1a patients the SVR12 rate was 26%.
  • Higher SVR12 rates were reported among patients who were rapid responders, i.e. those who achieved an eRVR2. Among patients with an eRVR2, 80% with G1b and 31% with G1a achieved SVR12.
  • IL28B genotype (CC and non-CC) appeared to have less impact on SVR12 rates relative to differences observed between HCV G1a and G1b patients.
  • Among patients not receiving RBV, breakthrough rates were higher indicating that RBV still plays an important role in preventing viral breakthrough.
  • All patients with a confirmed viral breakthrough showed DNV-resistant variants, while only one patient showed the NS5B S282T polymerase mutation associated with resistance to MCB.
  • Combination of MCB, DNVr and RBV is safe and well tolerated, resulting in no significant cytopenias, no treatment-emergent alanine aminotransferase elevations or any new signals with combination therapy.
  • In view of its promising efficacy in G1b patients (>70%) and its good tolerability and safety profile, this interferon-free regimen warrants further study.

References

1. Poordad F, McCone J Jr, Bacon BR, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 2011; 364: 1195–206

2. Jacobson IM, McHutchison JG, Dusheiko G, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med 2011; 364: 2405–16

3. Sherman K, Flamm SL, Afdhal NH, et al. Response-Guided Telaprevir Combination Treatment for Hepatitis C Virus Infection. N Engl J Med 2011; 365: 1014–1024

4. Gane EJ, Roberts SK, Stedman CA, et al. Oral combination therapy with a nucleoside polymerase inhibitor (RG7128) and danoprevir for chronic hepatitis C genotype 1 infection (INFORM-1): a randomised, double-blind, placebo-controlled, dose escalation trial. Lancet 2010; 376: 1467–75

5. Ali S, Leveque V, Le Pogam S, et al. Selected replicon variants with low-level in vitro resistance to the hepatitis C virus NS5B polymerase inhibitor PSI-6130 lack cross-resistance with R1479. Antimicrob Agents Chemother 2008; 52: 4356–69

6. Leveque V, Fung A, Le Pogam S. et al. Nucleoside analog R7128, a prodrug of PSI-6130, shows inhibition potency across HCV genotypes 1-6 in vitro. Poster P-215 presented at the 16th International Symposium on Hepatitis C Virus and Related Viruses, Nice, France; 2009. Poster 215

7. Reddy R, Rodriguez-Torres M, Gane E, et al. Antiviral activity, pharmacokinetics, safety, and tolerability of R7128, a novel nucleoside HCV RNA polymerase inhibitor, following multiple, ascending, oral doses in patients with HCV genotype 1 infection who have failed prior interferon therapy. Hepatology 2007; 46(4 suppl): 862A

8. Gottwein JM, Scheel TK, Jensen TB, et al. Differential efficacy of protease inhibitors against HCV genotypes 2a, 3a, 5a, and 6a NS3/4A protease recombinant viruses. Gastroenterology 2011;141: 1067–79

9. Imhof I, Simmonds P. Genotype differences in susceptibility and resistance development of hepatitis C virus to protease inhibitors telaprevir (VX-950) and danoprevir (ITMN-191). Hepatology 2011; 53: 1090–9

10. Gane EJ, Rouzier R, Stedman C, et al. Antiviral activity, safety, and pharmacokinetics of danoprevir/ritonavir plus PEG-IFN a-2a/RBV in hepatitis C patients. J Hepatol 2011; 55: 972–9

Presented at the International Liver CongressTM 2012 [47th Annual Meeting of the European Association for the Study of the Liver (EASL)], April 18-22, Barcelona, Spain
This research was funded by Roche
Support for third-party writing assistance for this presentation was provided by F. Hoffmann-La Roche Ltd.

Source

Gilead Sciences, Inc.
333 Lakeside Drive
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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