Program Schedule

1223
Ledipasvir/Sofosbuvir is Safe and Effective as a Single-Tablet-Regimen for Treatment of Patients with Genotype 1 Chronic Hepatitis C Virus, Including those with Compensated Cirrhosis

Session: Oral Abstract Session: Viral Infections: Clinical Trials and Pathogenesis
Friday, October 10, 2014: 2:15 PM
Room: The Pennsylvania Convention Center: 105-AB
Background: Simple, safe and effective treatment of genotype 1 (GT 1) chronic hepatitis C virus (HCV), without the use of pegylated-interferon (PegIFN) and ribavirin (RBV), remains an unmet medical need.  The once-daily single-tablet-regimen of Ledipasvir (LDV), an NS5A inhibitor, and sofosbuvir, an NS5B nucleotide polymerase inhibitor, resulted in high rates of sustained virologic response (SVR) in phase 2 studies.

Methods: Three open-label phase 3 clinical trials evaluated the safety and efficacy of LDV/SOF administered with or without (±) RBV for treatment of GT 1 chronic HCV. There was no upper limit to age or body mass index (BMI).  Treatment-naïve patients, including those with compensated cirrhosis, were randomized to 12 and 24 weeks of LDV/SOF ± RBV in the ION-1 study, while patients without cirrhosis were randomized to 8 weeks of LDV/SOF ± RBV or 12 weeks of LDV/SOF in the ION-3 study.  HCV treatment-experienced patients, including those with compensated cirrhosis and prior HCV protease-inhibitor (PI) failure, were randomized to 12 and 24 weeks of LDV/SOF ± RBV in the ION-2 study.  The primary endpoint was SVR at 12 weeks after the end of therapy (SVR12).

Results: Of the 1952 patients randomized and treated in these three phase 3 studies, 308 (16%) were African American, 224 (12%) had compensated cirrhosis, 591 (26%) had a BMI ≥ 30 kg/m2, 1597 (82%) had a high HCV viral load ≥ 800,000 IU/mL, and 440 (23%) were treatment-experienced.  Of these 440 treatment-experienced subjects, 231 (53%) were prior HCV protease-inhibitor (PI) + PegIFN + RBV treatment failures.  Overall, 97% of all patients achieved SVR12.  The intent-to-treat SVR12 rates in all treatment arms are show in Figure 1.  The most common adverse events (AEs) included fatigue, headache, nausea, and insomnia.  Majority of AEs occurred more frequently in the RBV-containing arms of the studies. 

Conclusion: A single-tablet-regimen of LDV/SOF, given once-daily, was highly effective in patients with genotype 1 HCV infection, including those with compensated cirrhosis and those who had previously failed triple therapy with a PI + PegIFN + RBV. The addition of RBV did not increase SVR rates but lead to higher rates of AEs.  

Mark Sulkowski, MD1, Kris Kowdley, MD2, Peter Ruane, MD3, Trevor Hawkins, MD4, Richard Elion, MD5, Kimberly Workowski, MD6, Anthony Mills, MD7, Mani Subramanian, MD, PhD8, Xiao Ding, PhD8, Star Seyedkazemi, PharmD8, Robert H. Hyland, D.Phil8, Jenny C. Yang, PharmD8, Phillip S. Pang, MD, PhD8, John G. Mchutchison, MD9, Nezam Afdhal, MD10 and David Wyles, MD11, (1)Johns Hopkins University School of Medicine, Baltimore, MD, (2)Virginia Mason Medical Center, Seattle, WA, (3)Peter J. Ruane, MD, Inc, Los Angeles, CA, (4)Southwest Care Center, Santa Fe, NM, (5)Whitman Walker Clin., Washington, DC, (6)Infectious Diseases, Emory University School of Medicine, Atlanta, GA, (7)Anthony Mills MD, Inc., Los Angeles, CA, (8)Gilead Sciences, Inc., Foster City, CA, (9)Gilead Sciences, Foster City, CA, (10)Beth Israel Deaconess Medical Center, Harvard University School of Medicine, Boston, MA, (11)Medicine, University of California San Diego, La Jolla, CA

Disclosures:

M. Sulkowski, Gilead: Investigator and Scientific Advisor, Consulting fee and Research support

K. Kowdley, Gilead Sciences: Investigator and Scientific Advisor, Consulting fee and Research support
AbbVie: Investigator and Scientific Advisor, Consulting fee and Research grant
Boeringer Ingelheim: Grant Investigator and Scientific Advisor, Consulting fee and Research support
Ikaria: Investigator and Scientific Advisor, Consulting fee and Research support
Janssen: Investigator and Scientific Advisor, Consulting fee and Research support
Merck: Investigator and Scientific Advisor, Consulting fee and Research support
Trio Health: Investigator and Scientific Advisor, Consulting fee and Research support
Novartis: Scientific Advisor, Consulting fee
Tekmira: Scientific Advisor, Consulting fee

P. Ruane, Gilead Sciences: Investigator, Scientific Advisor, Shareholder and Speaker's Bureau, Consulting fee, Research support and Speaker honorarium
Janssen: Investigator, Scientific Advisor and Speaker's Bureau, Consulting fee, Research support and Speaker honorarium
Boehringer Ingelheim: Investigator, Research support
AbbVie: Investigator and Scientific Advisor, Consulting fee and Research support

T. Hawkins, Gilead Sciences: Consultant, Investigator, Scientific Advisor and Speaker's Bureau, Consulting fee, Research support and Speaker honorarium
Janssen: Investigator and Scientific Advisor, Consulting fee and Research support
BMS: Investigator and Scientific Advisor, Consulting fee and Research support
GlaxoSmithKline: Investigator, Research support
Merck: Investigator, Research support
Sangamo: Investigator, Research support

R. Elion, Gilead: Investigator, Scientific Advisor and Speaker's Bureau, Consulting fee, Research support and Speaker honorarium
BMS: Consultant, Scientific Advisor and Speaker's Bureau, Consulting fee and Speaker honorarium
ViiV: Consultant, Investigator and Speaker's Bureau, Consulting fee, Research support and Speaker honorarium
Merck: Speaker's Bureau, Speaker honorarium
AbbVie: Investigator, Research support

K. Workowski, None

A. Mills, Gilead Sciences, Inc.: Consultant, Investigator and Speaker's Bureau, Consulting fee, Research support and Speaker honorarium
ViiV: Investigator, Research support
Pfizer: Investigator, Research support
Kowa : Investigator, Research support
Boehringer Ingleheim: Investigator, Research support
Serono: Investigator, Research support
Repros: Investigator, Research support
Sumagen: Investigator, Research support
GenProbe: Investigator, Research support
BMS: Investigator, Research support
Janssen: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
Merck: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium

M. Subramanian, Gilead Sciences, Inc.: Employee and Shareholder, Salary

X. Ding, Gilead Sciences, Inc.: Employee and Shareholder, Salary

S. Seyedkazemi, Gilead Sciences, Inc.: Employee and Shareholder, Salary

R. H. Hyland, Gilead Sciences, Inc.: Employee and Shareholder, Salary

J. C. Yang, Gilead Sciences, Inc.: Employee and Shareholder, Salary

P. S. Pang, Gilead Sciences, Inc.: Employee and Shareholder, Salary

J. G. Mchutchison, Gilead Sciences, Inc.: Employee and Shareholder, Salary

N. Afdhal, Gilead Sciences, Inc.: Investigator and Scientific Advisor, Consulting fee and Research support
Merck: Grant Investigator and Scientific Advisor, Consulting fee and Grant recipient
AbbVie: Grant Investigator and Investigator, Research grant and Research support
Janssen: Scientific Advisor, Consulting fee
Vertex: Investigator and Scientific Advisor, Consulting fee and Research support
BMS: Investigator and Scientific Advisor, Consulting fee and Research support
Springbank: Scientific Advisor and Shareholder, Consulting fee
Medgenics: Scientific Advisor, Consulting fee
Novartis: Scientific Advisor, Consulting fee
Boehringer Ingelheim: Scientific Advisor, Consulting fee
Idenix: DSMB, Consulting fee

D. Wyles, AbbVie, BMS, Gilead, Merck, Vertex Pharmaceuticals: Research Contractor, Research support
AbbVie, BMS, Gilead, Janssen: Scientific Advisor, Consulting fee

Findings in the abstracts are embargoed until 12:01 a.m. EDT, Oct. 8th with the exception of research findings presented at the IDWeek press conferences.

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