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EASL 2014: summary of interferon-free HCV studies with new DAAs

27 May 2014. Related: Conference reports, Other news, .

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Simon Collins, HIV i-Base and Tracy Swan, TAG

Numerous studies at the 2014 European Association for the Study of the Liver (EASL) meeting presented an impressive volume of new data, all moving steadily towards broadly curing HCV with effective and tolerable short course oral treatment.

The WHO and EASL both launched new treatment guidelines. EASL now recommend all the latest approved direct-acting antiviral (DAA)-based treatment, with the same indications and choice of treatments irrespective of HIV status. These first WHO guidelines to cover HCV treatment have been produced for low- and middle-income countries, where most people with hepatitis C in the world live.

Many companies have in-house combinations, some of which are already coformulated into fixed-dose combinations. Studies of the most advanced drugs in development reported dramatically high SVR12 (sustained virologic response rates twelve weeks after stopping treatment, equivalent to cure) in more than 95% of patients.This is from using 12 weeks treatment – and shorter treatment duration may also be possible.

Unlike HIV, baseline HCV drug resistance (hepatologists refer to RAPs and RAVs: resistance-associated polymorphisms and variants), is often easily overcome by treatment or not clearly related to treatment outcome. This is likely due to the higher viral potency of the drugs, the lack of an archived viral reservoir and the greater number of drugs to combine. However, there is currently little data to help understand the impact on subsequent treatment of emergent mutations or due to cross-resistance amoung drugs in the class.

Rapid viral clearance is now reported in patients both with compensated and decompensated liver disease, including people with prior treatment an DAA experience; after HCV recurrence after post-transplant; and in people with HIV/HCV coinfection.

Most of these drugs are extremely tolerable with very few serious side effects and few drug-related discontinuations.

Most combinations are mainly active against genotype 1. Sofosbuvir and GS-5816 from Gilead and daclatasvir by BMS have activity against the broadest range of genotypes. High SVR12 rates from combinations by other manufacturers may make treating G1 and 4 a more competitive market given the importance of drug pricing in access to treatment.

DAAs appear to have similar efficacy irrespective of HIV status. This was supported by HIV coinfection studies using combinations from Gilead and from Merck. It is also important that key studies using Gilead and AbbVie combinations were simultaneously published online in the New England Journal of Medicine (NEJM).

As a caution, some of the studies were presenting interim results and some data is tentative due to small patient numbers.

As with HIV, especially given the global burden of HCV, the success of treatment, needs to be matched by an approach to healthcare that will enable broad and affordable access. This was also highlighted at the meeting by a peaceful demonstration by activists who distributed pill capsules filled with gold glitter, together with leaflets and stickers based on the USD $1000 a day launch price of Gilead’s sofosbuvir: “Sovadi, So Expensive”.

Summary of results with key compounds by manufacturer

Sofosbuvir, ledipasvir and GS-5816 – Gilead

Sofosbuvir is already approved in Europe and the US. New results were presented for sofosbuivir in different populations, including patients with advanced liver disease (including decompensated cirrhosis and post-transplant recurrence), in people who previously used sofosbuvir and other DAAs, and in HIV coinfection. Sofosbuvir is active against all genotypes (but slightly less so against G3).

Ledipasvir (previously GS-5885) is mainly active against G1. Gilead has already produced a coformulation of sofosbuvir and ledipasvir (400 mg/90 mg) in one pill. Studies using the fixed dose combination (FDC) at EASL 2014 included first results in people with HIV/HCV coinfection.

GS-5816 is an NS5A inhibitor from Gilead that is active against genotypes 1 to 6 and produced SVR12 results >95% in a Phase 2 study with sofosbuvir (though few people had G 4, 5, and 6).

ABT-450/r/ABT-267, ABT-333 – AbbVie

The AbbVie “2D” combination includes ABT-450/ritonavir and ABT-267 (ombitasvir) coformulated in a once-daily pill (150 mg/100 mg/25 mg); AbbVie’s “3D” combination includes ABT-333 (dasabuvir) in a 250 mg twice-daily dose. High SVR12 rates (>95%), equally active in genotype 1a and 1b, including people previously treated with pegylated interferon and ribavirin. The SAPPHIRE I and II phase 3 studies, in G1 treatment-naïve and -experienced patients respectively, were published in the NEJM to coincide with EASL.

For genotype 4, ribavirin is used instead of ABT-333 (since it is only effective against genotype 1). The phase II PEARL study reported 100% SVR12 with ribavirin and 91% without, after 12 weeks treatment.

The TURQUOISE-II study using 3D + ribavirin in people with compensated cirrhosis reported impressive SVR12 rates of 92% and 96%, after 12 and 24 weeks of treatment, respectively.

MK-5172 (grazoprevir) and MK-8742 (elbasvir) – Merck

MK-5172 (NS3/4A protease inhibitor) and MK-8742 (NS5A inhibitor) are active against genotype 1, (with ongoing studies looking at other genotypes). New data was presented on use with and without ribavirin in people with compensated cirrhosis, prior treatment experience, and in HIV coinfection. A fixed dose single pill formulation (dose 100 mg/50 mg) has already been produced that will be used in phase 3 studies, and these studies will include people with Child-Pugh B cirrhosis.

A small HIV/HCV coinfection study (n=40) in HIV positive people on stable ART with high CD4 counts produced SVR4 results of 97% with ribavirin and 90% without. Future phase 3 studies will include HIV positive people, including in an opiate substitution study.

Daclatasvir, asunaprevir and BMS-791325 – BMS

Daclatasvir produced best results in combination with sofosbuvir (in research not supported by Gilead) but another study also looked at an all-BMS combinations of daclatasvir with asunaprevir (NS3 protease inhibitor) and BMS-791325 (non-nucleoside NS5B inhibitor).

The HALLMARK DUAL study in a mixed population (with and without cirrhosis) of genotype 1b treatment naïve, IFN-ineligible or intolerant and null-responders reported slightly less impressive results with greater than 80% SVR12 rates.

Asunaprevir is active against G1 and G4.

Phase 3 studies are underway in the US with daclatasvir and sofosbuvir for genotype 1, 2, 3 and 4 (the ALLY studies).

Simeprevir – Janssen

Simepravir is already licensed in the US and the EU. This is another compound studied with sofosbuvir (again, this research was not supported by Gilead).

At EASL 2014, final results and sub analyses from the COSMOS study were reported. Studies were also presented using simeprevir with pegylated interferon and ribavirin (of less interest and not reported in this article).

Faldaprevir and deleobuvir – Boehringer Ingelheim

Although several presentations included study results using faldaprevir, the associated side effects make it difficult to know whether this drug will have advantages over other DAAs.

Deleobuvir has already had development stopped due to high rates of side effect-related discontinuations. Active against genotype 1a. Studied with and without ribavirin. The only other DAA that faldaprevir has been tested with is PPI-668, an NS5A inhibitor (manufactured by Presidio).

Boehringer Ingelheim will not actively market faldaprevir which is expected to obtain approval in the EU this summer. Deleobuvir will not be further developed.

A summary of these studies is included in Table 1.

This table does not include information on other important factors – all of which affect results of ITT analyses. For example, side effects or the role of ribavirin (side effects are usually higher in study arms where ribavirin is included); for discontinuation due to these; or loss to follow-up for other reasons. Some studies only report interim data.

Table 1: Summary SVR rates in all-oral DAA-based studies at EASL 2014
Drugs and duration Population studied, genotype, duration Summary results Abstract & reference
Gilead: Genotype 1-6 for sofosbuvir and GS-5816, ledipasvir mainly active against G1
sofosbuvir/ledipasvir FDC (400/90 mg).ELECTRON-II study.12 weeks. G1 with decompensated cirrhosis (n=20); G1 with sofosbuvir experienced (n=19); G3 (n=51). SVR12:65% (13/20) in decompensated cirrhosis;100% (19/19) in experienced;100% (26/26) in G3 with ribavirin O6.Gane E et al.[1]
sofosbuvir + ribavirin +/- PEG-IFN. Open label. 12 weeks with 3 drugs or 24 weeks with 2 drugs. Investigator choice to use PEG-IFN. G2 (n=16), G3 (n=97)sofosbuvir experienced.12 weeks SOF + IFN + RBV (n=34) and 24 weeks with SOF + RBV only (n=73). Interim data for people who have SVR12 data:92% (24/26) using sofosbuvir with pegylated interferon + ribavirin vs 63% (25/40) using sofosbuvir + ribavirin.Better responses with PEG-IFN and ribavirin for 12 weeks for both G2 and G3 and for people with and without cirrhosis. O8Esteban R et al.[2]
sofosbuvir/ledipasvirSYNERGY study.12 weeks. G1 (n=14)Treatment experienced. Small NIH study reporting high SVR12 rates in people who previously used sofosbuvir.SVR12: 100% (14/14) O11.Osinusi A et al. [3]
sofosbuvir/ledipasvir FDC – HIV coinfection.ERADICATE study.12 weeks. G1 (n=50; 13 with F3).HCV treatment naïve.HIV/HCV coinfected (n=37 on ART, n=13 no ART). Interim results only. SVR4: 100% irrespective of ART use (12/12 not on ART and 22/22 on ART).SVR12: 100% (10/10) not on ART O14.Osinusi A et al.[4]
sofosbuvir + PEG-IFN + ribavirin.Open label.12 weeks. G1a and 1b (n=80)Treatment experienced (including with resistance from prior use of DAAs) Interim data for 67 patients with SVR12 data, 13 are still on treatment. SVR12: 74% (37/50).Response by prior treatment: NS3 only: 50% (6/12); NS3 + NS5a: 75% (18/24); NS3 + NS5a + NS5b: 93% (13/14).Number of mutations was not related to response. O55.Pol S et al.[5]
sofosbuvir/ledipasvir FDC +/- ribavirinRandomised to +/-RBV for 8 weeks or no-RBV for 12 weeks.ION-3 study. G1n=647treatment-naïve.non cirrhotic. SVR12:94% (95%CI: 90 to 97) with 8 weeks without ribavirin.93% (95%CI: 89 to 96) with 8 weeks with ribavirin,95% (95%CI: 92 to 98) with 12 weeks without ribavirin.Results showed 8 week without ribavirin to be non-inferior. O56. Kowdley KV et al.[6]
sofosbuvir + ribavirin +/- peg-IFN.Open label. Compassionate access.Investigator choice of PEG-IFN.Up to 48 weeks. G 1, 2, 3, 4 and mixed (n=87 post-transplant). High risk patients (life expectancy < 1 year): n=48 early recurrence post-transplant and 56 compensated and non-compensated cirrhosis including cholestatic fibrosis. SVR12: overall 62% (53/85)>50% with SOF+RBV and 44% with SOF+RBV+PEG-IFN.Death and transplant excluded.62% also had improved symptoms.13 deaths, 8 on treatment.”Spectacular results in patients with acute recurrence – better than chronic cirrhosis”.

22/100 used PEG-IFN, with results not yet analysed.

 O62.Forns X et al.[7]
sofosbuvir + ribavirin vs observation only as control for 24 weeks until roll-over to active arm. Randomised.48 weeks treatment. G 1, 2, 3, 4 (most G1, n= 2 for each of G2, G3 and G4).n=50 (25 each arm).Included cirrhosis with portal hypertension (CBT 5-6 compensated and CPT 7-9, decompensated). Interim week 24 analysis – ie active 24 weeks and end of observational period. Only virologic and safety responses available. No SVR data as still on treatment.CPT 5-6: 50% undetectable at week 2, 100% from week 4.CPT 7-9: 75% by week 4 and 94% later.MELD score dropped in both active and placebo but improvement in liver function was greater in the active arm. O68.Afdhal N et al.[8]
sofosbuvir/ledipasvir FDC +/- ribavirin.Randomised to use of ribavirin and duration:12 or 24 weeks.ION-2 study. G1a and 1b (n=440)Treatment experienced.20% with cirrhosis Stratified by subtype, cirrhosis and prior response.SVR12: 96% and 99% with ribavirin (12 and 24 week).SVR12: 94% and 99% without ribavirin (12 and 24 week).In patients with cirrhosis, SVR12 with and without ribavirin was 82% and 86% with 12 weeks treatment and 100% irrespective of ribavirin use with 24 weeks treatment. O109. Afdhal N et al.[9]
sofosbuvir + GS-5816 (NS5A inhibitor)Randomised to open label GS-5816 dose.12 weeks. G1-6 (mainly G1a, 2 and 3; n=154)G1=55, G2=21, G3=54, G4=14, G5=1, G5 and G6=9.Treatment naïve.No cirrhosis. Phase 2 dose ranging (25 mg and 100 mg for GS-5816).SVR12: 95% (73/77) with 25 mg and 96% (74/77) with 100 mg.SVR12 results by genotype were: G1 (96% and 100%), G2 (91% and 100%), G3 (93% and 93%), G4 (100% vs 87%), G5 (100%) and G6 (100% vs 100%) in the 25 mg and 100 mg arms respectively. O111.Everson GT et al.[10]
sofosbuvir/ledipasvir FDC +/- ribavirin.Randomised to ribavirin and duration: 12 or 24 weeks. ION-1 study. G1a and 1bN=865Treatment-naïve16% cirrhotic (Child A) SVR12: 97%-99% across four arms.No differences by ribavirin use or duration.Similar responses in cirrhotic and non-cirrhotic – 94%-100%. O164.Mangia A et al.[11]
AbbVie: 3D (ABT-450/r/ABT-267 + ABT-333): G1 and G4, plus ribavirin
Abbott 3D (ABT-450/r/ABT-267 + ABT-333) + ribavirin vs matching placebo for 12 weeks (then open label active). 48 weeks follow-up.SAPHIRE II G1a and 1b (n=394; 297 active and 97 placebo)PEG+RBV-experiencedNo cirrhosis. SVR12: 96.3% (95% CI: 94.2% – 98.4%).Similar for both G1a and 1b and for all PEG-IFN response groups.(~95% for relapsers and prior null response and 100% for partial response). O1.Zeuzem S et al.[12]
AbbVie 2D +/-ribavirin.12 weeks.PEARL I G4 – treatment naïve: (n=96; n=44 with RBV and n=42 without RBV).PEG-IFN + RBV experienced: (n=49). No cirrhosis. Phase II study.Treatment naïve:SVR12: 100% 2D + ribavirin vs 91% 2D onlyPEG-IFN experienced:SVR4: 100% O58. Hezode C et al.[13]
AbbVie 3D + ribavirin for 12 weeks vs matching placebos for 12 weeks (then roll-over to open label). 48 weeks f/u in all.12 weeks. SAPPHIRE I G1 (n=631; active arm 473 and 178 placebo).45% women.F2 and F3 (68%) SVR12: >95%SVR12 (initial randomisation): 96% (455/473)No difference by G1a vs 1b (both >95%) O60.Feld JJ et al.[14]
AbbVie 3D + ribavirin.Open label.24 weeks. G1 (n=34)Non-cirrhotic transplant recipients with recurrent HCV.>12 months post-transplant, naïve since transplant. Interim analysis.To date, all patients achieved RVR (34/34) and EOTR (13/13).Current SVR4 is 97% (32/23).Current SVR12: 96% (25/26). O144.Kwo P et al.[15]
AbbVie 3D + ribavirin open label, randomised to duration.12 or 24 weeks.TURQUOISE II G1a and 1b (n=380; 12 week n=208 and 24 week n=172)Naïve (42%) and experienced (58%).cirrhotic (Child Pugh A) SVR12: 92% with 12 weeks (191/208) and 24 weeks (165/172).G1a: 88% and 94% by 12 and 24 week.G1b: 98% and 100% by 12 and 24 week.Naïve (92% and 93%; prior relapse (93% and 100%), prior partial response (100% and 100%) and prior null response (80% and 92%). LB O163.Poordad F et al.[16]
AbbVie 3D + ribavirin +/- randomised to ribavirin or placebo.PEARL-III G1b (n=419)treatment-naive >99.5% SVR with or without ribavirin.No relapsers or failure in the non-ribavirin group. LB P1299.Ferenci P et al.[17]
Merck/MSD: MK-5172, MK-8742 – G1, naïve and experienced, with ribavirin. Also HIV/HCV coinfection.
MK-5172 (100mg)/MK-8742 (dose finding) +/- ribavirin.8 and 12 weeks.C-WORTHy. study. G1 a and 1b (n=94)Part A: (n=65) 12 week dose-finding study for MK-8742; Part B (n=91) using 50 mg dose included an 8 week arm (n=30). Treatment naïve, non-cirrhotic. Note: SVR12: 96%-100% rates were reported for Part A at AASLD 2103.SVR12: 94%-100% in Part A, with or without ribavirin, after 12 weeks treatment. No differences were seen for G1a compared to 1b or by use of ribavirin. SVR4-8: 83% (25/30) after 8 weeks treatment. O10.Herzode C et al.[18]
MK-5172 (100 mg) + MK-8742 (50 mg) +/- ribavirin.12 or 18 weeks.C-WORTHy. study G1 (n=253).Include naïve with compensated cirrhosis (n=123) and experienced +/- cirrhosis (n=130) Abstract report 94-100% virological response.Interim results. SVR4-8: 90-97% cirrhotic. SVR4-8: 91-100% in non-responders. No difference with or without ribavirin. No difference in G1a vs G1b.SVR4-8: Naïve cirrhotic: 90-97% at 12 weekand 97% in 18 week.SVR4-8: experienced: 91-94% – 12 week treatment and 100% with 18 weeks. Duration will be a variable in phase 3 studies. O61.Lawitz E et al.[19]
MK-5172 (100 mg) + MK-8742 (50 mg) + ribavirin.12 weeks.C-WORTHy. study. G1 (n=59; n=29 with RBV and 30 without)HIV/HCV coinfection.On raltegravir-based ART (high CD4 > 600). HCV-naïve.Non cirrhotic. SVR4: 90-97%With ribavirin: 97% (28/29)Without ribavirin: 90% (26/29) O63.Sulkowski M et al.[20]
MK-5172 + ribavirinRandomised to duration.12 or 24 weeks.C-SPIRIT study. G1 (with IL28B CC genotype).n=26.Non-cirrhotic. People unsuppressed at week 12 roll over to extended 24 weeks treatment.In people using 24 weeks treatment:SVR4 in 13/17 (76%)SVR12 10/16 (63%) P1233.Gane E et al.[21]
BMS: dalcatasvir, asunaprevir and BMS-791325
daclatasvir + sofosbuvir +/- ribavirinSome patients used 7-day lead-in with sofosbuvir monotherapy.12 or 24 weeks. G1,2,3Mixed naïve and experienced.n=211 (n=126 G1 naïve; n= 44 G2 or 3 naïve; n=41 G1 non responders to PEG+RBV with either boceprevir or telaprevir.non-cirrhotic Note: SVR12 results of 98-100% from this study were previously published in NEJM on 16 January 2013 (doi: 10.1056/NEJMoa1306218).This new analysis was based on resistance results. No apparent impact of NS5a RAPs at baseline and not pattern between mutation and failure.G1a: 24/97 had RAPs at baseline all achieved SVR12. G1b: 13/25 had RAPs at baseline all achieved SVR12. G2 – 23/23 had RAPs at baseline all had SVR12. G3 – 11/18 had RAPs at baseline – one relapsed.Three G1 relapsers were in the sofosbuvir. lead-in group – one SVR after PEG-IFN and ribavirin salvage. O64.McFee F et al.[22]
daclatasvir + asunaprevirvs placebo24 weeks.HALLMARK DUAL study. G1bRandomised DCV 60 mg QD plus ASV 100 mg BID in naïve (n=203) vs placebo (n = 102).Open label for prior null responder (n=205) and intolerant (n=235). SVR12:91% in naïve82% no responders83% intolerant/ineligible.No difference in response by cirrhosis (84%; n = 206 with cirrhosis vs 85% in 437 without cirrhosis).No difference by treatment experience or IL28 genotype. O166. Manns M et al.[23]LB P1300. Kao J-H et al.[24]
daclatasvir, asunaprevir and BMS-791325 (75 and 150 mg) G4 (n=21)12 weeks Randomisation for BMS-79135 doses.SVR in 11/12 and 9/10 in 75 mg and 150 mg arms respectively.92% SVR12. P1133. Hassenein et al.[25]
daclatasvir (60 mg) + VX-135 (100 mg or 200 mg). N=23 Small dose-finding study of NS5B inhibitor VX-135 (100 mg and 200 mg)SVR12 in 83% and 91%, respectively.Note: further investigation into the 200 mg dose of VX-135 is currently halted by the FDA in the US. Although promising, it’s future is therefore uncertain. LB P1303.Gane E et al.[26]
Janssen: simeprevir – G1, used with PEG-INF, ribavirin and Gilead’s sofosbuvir
simeprevir + sofosbuvir +/- ribavirin.Randomised to +/- ribavirin open label and 12 or 24 weeks.COSMOS study (Cohort I) G1a and 1b (n=80).Prior null responders.Metavir stage 0-2. Subset analysis of Phase 2 COSMOS study.12 weeks treatment: SVR12: 96% (26/27) with ribavirin and 93% (13/14) without ribavirin.24 weeks treatment:SVR12: 79% (19/24) with ribavirin and 93% (14/15) without ribavirin.The Q80K polymorphism at baseline and having the IL28 TT genotype appeared to predict risk of non-response. O7.Sulkowski M et al.[27]
simeprevir + sofosbuvir +/- ribavirin.Randomised to +/- ribavirin open label and 12 or 24 weeks.COSMOS study (Cohort II) G1a and 1b (n=87).Naïve and prior null-responders.Metavir stage 3/4. Subset analysis of Phase 2 COSMOS study.93% in 12 week arm (25/27 with ribavirin and 13/14 without ribavirin).93% and 100% in 24 week arm (28/30 with ribavirin and 16/16 without ribavirin.No difference by cirrhosis stage, treatment history or G1 subtype (1a vs 1b). LB O165.Lawitz E et al.[28]
Boehringer ingelhiem: faldaprevir, deleobuvir (since terminated): G1a +/- ribavirin
faldaprevir (BI) and deleobuvir (BI, since terminated), PPI-668 (Presidio) +/- ribavirin.12 weeks. G1a (n=36).Treatment naïve. Non-cirrhotic. Three arms – cohort 1 and 2: 400 mg or 600 mg faldaprevir. cohort 3 used PPI-668 instead of ribavirin. Cohort 1 and 2: SVR12: 92% (22/24)Cohort 3: SVR12: 75% (9/12, 2 replacements).Good virological responses irrespective or ribavirin use but difficult side effects – 75% nausea, GI etc and 18% photosensitivity despite use of sunscreen. Side effects were lower grade without ribavirin, but these patients were also more likely to stop. O65.Lalezari J et al.[29]

References:

Unless stated otherwise, all references are to the Programme and Abstracts from the 49th Annual Meeting of the European Association for the Study of the Liver (EASL), 9-13 April 2014, London. The abstract book is available for free download as a PDF file.

http://www.ilc-congress.eu

Although EASL do not post webcasts or slides online, slides are posted to NATAP.org with hyperlinks in the references below.

  1. Gane E et al. Sofosbuvir/ledipasvir fixed dose combination is safe and effective in difficult to treat populations including geneotype-3 patients, decompensated genotype-1 patients and genotype-1 patients with prior sofosbuvir treatment experience. 49th EASL, 9-13 April 2014, London. Oral abstract O6.
    http://www.natap.org/2014/EASL/EASL_23.htm
  2. Esteban R et al. Successful retreatment with sofosbuvir-containing regimens for HCV genotype 2 or 3 infected patients who failed prior sofosbuvir plus ribavirin therapy. 49th EASL, 9-13 April 2014, London. Oral abstract O8.
    http://www.natap.org/2014/EASL/EASL_37.htm
  3. Osinusi A et al. Retreatment of relapsers to sofosbuvir/ribavirin with sofosbuvir/ledipasvir: complete and rapid virologic suppression by week 4. 49th EASL, 9-13 April 2014, London. Oral abstract O11.
    http://www.natap.org/2014/EASL/EASL_07.htm
  4. Osinusi A et al. Use of sofosbuvir/ledipasvir fixed dose combination for treatment of HCV genotype-1 in patients coinfected with HIV. 49th EASL, 9-13 April 2014, London. Oral abstract O14.
    http://www.natap.org/2014/EASL/EASL_05.htm
  5. Pol S et al. Successful retreatment with sofosbuvir of HCV genotype-1 infected patients who failed prior therapy with peginterferon + ribavirin plus 1 or 2 additional direct-acting antiviral agents. 49th EASL, 9-13 April 2014, London. Oral abstract 55.
    http://www.natap.org/2014/EASL/EASL_42.htm
  6. Kowdley KV et al. Sofosbuvir/ledipasvir with and without ribavirin for 8 weeks compared to sofosbuvir/ledipasvir for 12 weeks in treatment-naïve non-cirrhotic genotype-1 HCV infected patients: the phase 3 ION-3 study. 49th EASL, 9-13 April 2014, London. Oral abstract 56. Published in NEJM: Kowdley K et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. NEJM 11 April 2014. DOI: 10.1056/NEJMoa1402355.
    http://www.nejm.org/doi/full/10.1056/NEJMoa1402355
  7. Forns X et al. Sofosbuvir compassionate use program for patients with severe recurrent hepatitis C including fibrosing cholestatis hepatitis following liver transplantation. 49th EASL, 9-13 April 2014, London. Oral abstract O62.
    http://www.natap.org/2014/EASL/EASL_41.htm
  8. Afdhal N et al. Sofosbuvir and ribavirin for the treatment of chronic HCV with cirrhosis and portal hypertension with and without decompensation: early virologic response and safety. 49th EASL, 9-13 April 2014, London. Oral abstract O68.
    http://www.natap.org/2014/EASL/EASL_19.htm
  9. Afdhal N et al. All oral fixed-dose combination sofosbuvir/ledipasvir with or without ribavirin for 12 or 25 weeks in treatment-experienced genotype 1 HCV-infected patients: the phase 3 ION-2 study. 49th EASL, 9-13 April 2014, London. Oral abstract O109.
    http://www.natap.org/2014/EASL/EASL_31.htm
    Published in NEJM: Afdal N et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. NEJM 12 April 2014. DOI: 10.1056/NEJMoa1316366.
    http://www.nejm.org/doi/full/10.1056/NEJMoa1316366
  10. Everson GT et al. Safety and efficacy of treatment with the interferon-free combination of sobosbuvir + GS-5816 for 12 weeks in treatment naïve patients with genotype 1-6 HCV infection. 49th EASL, 9-13 April 2014, London. Oral abstract O111.
    http://www.natap.org/2014/EASL/EASL_29.htm
  11. Mangia A et al. All oral fixed-dose combianation sofosbuvif/ledipasvir with or without ribavirin for 12 or 24 weeks in treatment-naïve genotype 1 HCV-infected HCV-infected patients the phase 3 ION-1 study.
    49th EASL, 9-13 April 2014, London. Oral late breaker LB O164.
    http://www.natap.org/2014/EASL/EASL_28.htm
    Also published in NEJM: Afdhal N et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. NEJM 12 April 2014. DOI: 10.1056/NEJMoa1402454.
    http://www.nejm.org/doi/full/10.1056/NEJMoa1402454
  12. Zeuzem S et al. Sapphire II: Phase 3 placebo-controlled study of interferon-free 12 week regimen of ABT-450/r/ABT-267, ABT-333 and ribavirin in treatment-experienced adults with hepatitis C virus genotype 1. 49th EASL, 9-13 April 2014, London. Oral abstract O1.
    http://www.natap.org/2014/EASL/EASL_03.htm
    Published in NEJM: Zeuzem S et al. Retreatment of HCV with ABT-450/r–ombitasvir and dasabuvir with ribavirin. NEJM 10 April 2014. OI: 10.1056/NEJMoa1401561.
    http://www.nejm.org/doi/pdf/10.1056/NEJMoa1401561
  13. Herzode C et al. Results from the phase 2 PEARL-I study: interferon-free regimens of ABT-450/R + ABT-267 with or without ribavirin in patients with HCV genotype 4 infection. 49th EASL, 9-13 April 2014, London. Oral abstract O58.
    http://www.natap.org/2014/EASL/EASL_09.htm
  14. Feld JJ et al. Sapphire I: Phase 3 interferon-free, 12 week regimen of ABT-450/r/ABT-267, ABT-333 and ribavirin in treatment-naive adults with hepatitis C virus genotype 1. 49th EASL, 9-13 April 2014, London. Oral abstract O60. Published in NEJM: Feld JJ et al. Treatment of HCV with ABT-450/r–ombitasvir and dasabuvir with ribavirin. NEJM 11 April 2014. DOI: 10.1056/NEJMoa1315722.
    http://www.nejm.org/doi/pdf/10.1056/NEJMoa1315722
  15. Kwo P et al. Results of the phase study M12-999: interferon-free regimen of ABT-450/R/ABT-267 + ABT-333 + ribavirin in liver transplant recipients with recurrent HCV genotype 1 infection. 49th EASL, 9-13 April 2014, London. Oral abstract O114.
    http://www.natap.org/2014/EASL/EASL_30.htm
  16. Poordad F et al. TURQUOISE-II: SVR12 rates of 92-95% in 380 hepatitis C virus genotype-1 infected adults with compensated cirrhosis rates of treated with ABT-450/R/ABT-267 and ABT-333 plus ribavirin (3D+RBV). Oral late breaker LB O163.
    http://www.natap.org/2014/EASL/EASL_27.htm
    Published in the NEJM: Poordad F et al. ABT-450/r–ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis. NEJM 12 April 2014. DOI: 10.1056/NEJMoa1402869.
    http://www.nejm.org/doi/full/10.1056/NEJMoa1402869
  17. Ferenci P et al. PEARL III: 12 weeks of ABT-450/R/267 + ABT-333 achieved SVR in >99% of treatment-naïve HCV genotype 1b-infected adults without or without ribavirin. 49th EASL, 9-13 April 2014, London. Late breaker poster abstract P1299.
  18. Herzode C et al. Safety and efficacy of the all-oral regimen of MK-5172/MK-8742 +/- ribavirin in treatment-naïve, non-cirrhotic, patients with hepatitis C genotype 1 infection: the C-WOTHY study. 49th EASL, 9-13 April 2014, London. Oral abstract O10.
    http://www.natap.org/2014/EASL/EASL_43.htm
  19. Lawitz E et al. Efficacy and safety of MK-5172 and MK-8742 ± ribavirin in hepatitis C genotype 1 infected patients with cirrhosis or previous null-response: the C-WORTHY study. 49th EASL, 9-13 April 2014, London. Oral abstract 60.
    http://www.natap.org/2014/EASL/EASL_21.htm
  20. Sulkowski M et al. Efficacy and safety of the all-oral regimen, MK-5172/MK-8742 +/− ribavirin for 12 weeks in GT1 HCV/HIV coinfected patients: the C-WORTHY study. 49th EASL, 9-13 April 2014, London. Oral abstract 63.
    http://www.natap.org/2014/EASL/EASL_15.htm
  21. Gane E et al. Efficacy and safety of MK-5172 plus ribavirun in treatment-naïve patients with hepatitis C virus genotype 1 infection: final results of the C-SPIRIT study. 49th EASL, 9-13 April 2014, London. Poster abstract 1233.
  22. McPhee F et al. Effect of baseline NS5A polymorphisms on virologic response to the all-oral combinations of daclatasvir + sofosbuvir +/- ribavirin in patients with chronic HCV infection. 49th EASL, 9-13 April 2014, London. Oral abstract O64.
    http://www.natap.org/2014/EASL/EASL_18.htm
  23. Manns M et al All-oral dual therapy with daclatasvir and asunaprevir in patients with HCV genotype 1b infections: phase 3 study results. 49th EASL, 9-13 April 2014, London. Oral abstract O166.
    http://www.natap.org/2014/EASL/EASL_25.htm
  24. Kao JH et al. Efficacy and safety of daclatasvir in combination with asunaprevir (DCV+ASV) in cirrhotic and non-cirrhotic patients with HCV genotype 1b: results of the HALLMARK DUAL study. 49th EASL, 9-13 April 2014, London. Late breaker poster abstract P1300.
    http://www.natap.org/2014/EASL/EASL_45.htm
  25. Hassanein T et al. All-oral therapy with daclatasvir in combination with asunaprevir and BMS-791325 for treatment-naïve patients with chronic HCV genotype 4 infection. 49th EASL, 9-13 April 2014, London. Poster abstract P1163.
  26. Gane E et al. An interferon- and ribavirin-free 12-week regimen of once-daily VX-135 and daclatasvir in treatment-naïve patients with genotype 1 HCV infection. 49th EASL, 9-13 April 2014, London. Late breaker poster P1303.
  27. Sulkowski M et al Once-daily simeprevir (TMC435) plus sofosbuvir (GS-7977) with or without ribavirin in HCV genotype 1 prior null responders with Metavir F0-2: COSMOS study subgroup analysis. 49th EASL, 9-13 April 2014, London. Oral abstract O7.
    http://www.natap.org/2014/EASL/EASL_46.htm
  28. Lawitz E et al. Simeprevir plus sofosbuvir with/without ribavirin in HCV genotype 1 prior null-responder/treatment-naïve patients (COSMOS study): primary endpoint (SVR12) results in patients with Metavir F3-4 (cohort 2). 49th EASL, 9-13 April 2014, London. Late breaker oral abstract 165.
    http://www.natap.org/2014/EASL/EASL_26.htm
  29. Lalezari J et al. High rate of sustained virologic response in patients with HCV genotype-1a infections: a phase 2 trial of faldaprevir, deleobuvir and PPI-668 with and without ribavirin. 49th EASL, 9-13 April 2014, London. Oral abstract O65.
    http://www.natap.org/2014/EASL/EASL_36.htm

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