EASL 2014 - CARE Liver Disease Faculty - LBA O164: The Phase 3 ION-1 Study

All Oral Fixed-Dose Combination Sofosbuvir/Ledipasvir With Or Without Ribavirin For 12 Or 24 Weeks In Treatment-Naive Genotype 1 HCV-Infected Patients

A. Mangia,1 P. Marcellin,2 P. Kwo,3 G.R. Foster,4,5 M. Buti,6 N. Bräu,7 A. Muir,8 J.C. Yang,9 H. Mo,9 X. Ding,9 P.S. Pang,9 W.T. Symonds,9 J.G. McHutchison,9 S. Zeuzem,10 N. Afdhal,11

Background and Aims: The Phase 3 ION-1 study is evaluating whether the fixed-dose combination of sofosbuvir 400mg/ledipasvir 90mg (SOF/LDV) can effectively treat a population of treatment-naïve patients with genotype 1 HCV-infection and to determine if ribavirin (RBV) or longer treatment duration is required to achieve a high SVR rate.

Results: 865 patients were treated; baseline characteristics and SVR rates are shown in the table. In the 12-Week groups combined (n=431), a total of 11 (2.5%) patients failed to achieve SVR, with only 1 patient that relapsed and 10 patients that were lost to follow-up. Efficacy from the 24 Week groups (n=434) will be presented. The most frequent AEs reported for SOF/LDV were headache (25%), fatigue (23%), and nausea (12%). Thirty-two patients (4%) had treatment-emergent SAEs. No patients receiving 12-Weeks of treatment and 10 patients receiving 24-Weeks of treatment, discontinued therapy due to an AE. No AE leading to discontinuation occurred in >1 patient. Hemoglobin < 10 g/dL occurred in 8% of patients taking SOF/LDV+RBV and no patients taking SOF/LDV. No other significant laboratory abnormalities were observed.

Conclusions: A single tablet regimen of sofosbuvir/ledipasvir administered once daily for 12 weeks is highly effective and well tolerated in treatment-naïve, genotype 1, HCV-infected patients, including those with cirrhosis. The addition of RBV did not enhance the SVR rate.

Table 1. Response during and after treatment

In Canada, interferon-free, all oral antiviral regimens are approved only for the treatment of HCV genotypes 2 and 3. The sofosbuvir/ledipsasvir combination regimen studied in the ION-1 trial will likely be the first all oral therapy approved for patients with HCV genotype 1, which represents the majority in Canada. The ION-1 study convincingly demonstrates that a 12-week course of this once daily, single tablet regimen has a very favourable safety profile and leads to a sustained virologic response in nearly all (99%) previously untreated patients, including those with cirrhosis. The addition of ribavirin and extension of therapy to 24 weeks are of no benefit yet lead to added toxicity. As supported by the subsequent ION-3 phase 3 trial (Kowdley et al., EASL Abstract O56), further shortening of sofosbuvir/ledipasvir combination therapy to 8 weeks (without ribavirin) will be possible for treatment-naïve, non-cirrhotic patients with HCV genotype 1.
— CARE Liver Disease Faculty Perspectives

1Unità di Epatologia, Ospedale Casa Sollievo della Sofferenza, Foggia, Italy, 2Service Hépatologie, Hôpital Beaujon, Ile-de-France, France, 3Indiana University School of Medicine, Indianapolis, IN, United States,4Royal London Hospital, Barts Health NHS Trust, 5Grahame Hayton Unit, Ambrose King Cent, London, United Kingdom, 6Hospital Universitario Vall d'Hebron, Barcelona, Spain, 7Bronx Veteran's Affairs Medical Center, Bronx, NY, 8Duke University, Durham, NC, 9Gilead Sciences, Inc., Foster City, CA, United States, 10Medizinische Klinik 1, Klinikum der Johann Wolfgang-Goethe-Universität, Frankfurt am Main, Germany,11Beth Israel Medical Center, Boston, MA, United States