1785. Sofosbuvir/Velpatasvir Plus GS-9857(100MG) for 6, 8, or 12 Weeks in Genotype 1-6 HCV-Infected Patients: An Integrated Analysis of Safety and Efficacy from Two Phase 2 Studies
Session: Oral Abstract Session: HCV Advances
Saturday, October 29, 2016: 10:30 AM
Room: 388-390
Background: Sofosbuvir (SOF)/Velpatasvir (VEL) & GS-9857 are pangenotypic, potent direct-acting antiviral agents (DAAs) with high barriers to resistance. Combination therapy with these three drugs may be an effective treatment option for patients who failed prior treatment with direct-acting antiviral agents (DAAs) and also their potency may offer an opportunity to shorten treatment duration to less than 12 weeks for selected patients. These DAAs were evaluated in both TN & treatment-experienced (TE) genotype (GT) 1-6 HCV-infected patients with or without cirrhosis. This post-hoc analysis assesses safety and efficacy of the two Phase 2 studies.

Methods: TN patients received open-label SOF/VEL (400mg/100mg) + GS-9857 (100mg) administered orally once daily for 6 or 8 weeks based on the absence/presence of cirrhosis, respectively. Patients with virologic failure to prior treatment with pegylated-interferon (Peg-IFN) + RBV (GT2-6) or any DAA (GT2-6), NS5A-inhibitor or multiple classes of DAAs (GT1) ± Peg-IFN ± RBV regimens received open-label SOF/VEL+GS-9857 for 12 weeks. The primary endpoint was SVR12 (LLOQ=15 IU/mL). NS5A, NS3, and NS5B regions were amplified and deep sequenced (<1% cutoff) at baseline and at the time of virologic failure.

Results: A total of 258 patients (50% GT1, 13% GT2, 29% GT3, 6% GT4 and 2% GT6) were treated: 66% male, 82% white, 70% with non-CC IL28B allele(s), and 48% with cirrhosis. Baseline resistance-associated variants (RAVs) were detected in 55% of TN patients and in 60% of TE patients. SVR12 rates by treatment duration and genotype are shown in Table 1. Reported adverse events (AE >10%) were headache, fatigue, diarrhea, & nausea & were mild or moderate in severity. Three (1%) patients discontinued therapy due to AE(s); all 3 achieved SVR. No clinically significant laboratory abnormalities were observed.

Conclusion: Treatment with SOF/VEL + GS-9857 administered once daily to GT 1-6 HCV-infected patients was safe, well tolerated, and highly effective in TN patients with cirrhosis treated for 8 weeks and in TE patients, including those previously treated with DAAs, treated for 12 weeks. The 6 week treatment duration was associated with a higher relapse rate.

Ronald Nahass, MD, FIDSA, FSHEA1, Eric Lawitz, MD2, Ira M. Jacobson, MD3, Paul Kwo, MD4, Mindie Ngyuyen, MD5, Jenny C. Yang, PharmD6, Luisa Stamm, MD, PhD6, Sophia Lu, PhD6, Hadas Sobol, PhD6, Sarjita Naik, PharmD6, Joe Llewellyn, PharmD6, Diana Brainard, MD6, John G. Mchutchison, MD6, Michael Curry, MD7, Kris Kowdley, MD8, Nancy Reau, MD, FAASLD, AGAF9 and Edward Gane, MD10, (1)ID Care, Inc., Hillsborough, NJ, (2)Texas Liver Insititute, University of Texas Health Science Center, San Antonio, TX, (3)Mt Sinai Beth Israel, New York, NY, (4)Gastroenterology/Hepatology Division, Indiana University School of Medicine, Indianapolis, IN, (5)Standford University Medical Center, Stanford, CA, (6)Gilead Sciences, Foster City, CA, (7)Harvard, Boston, MA, (8)Liver Care Network and Organ Care Research, Swedish Medical Center, Seattle, WA, (9)Rush University Medical Center, Chicago, IL, (10)Liver Unit, Auckland Hospital, Auckland, New Zealand

Disclosures:

R. Nahass, Gilead: Scientific Advisor , Consulting fee and Research grant
Merck: Scientific Advisor , Consulting fee and Research grant
BMS: Scientific Advisor , Consulting fee

E. Lawitz, gilead: Grant Investigator , Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Research grant , Research support and Speaker honorarium
Abbvie: Grant Investigator , Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Research grant , Research support and Speaker honorarium
Merck: Grant Investigator , Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Research grant , Research support and Speaker honorarium
BMS: Grant Investigator , Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Research grant , Research support and Speaker honorarium
Janssen: Research Contractor , Scientific Advisor and Speaker's Bureau , Consulting fee , Research grant , Research support and Speaker honorarium

I. M. Jacobson, Gilead: Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Research grant and Speaker honorarium
BMS: Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Research grant and Speaker honorarium
Abbvie: Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Research grant and Speaker honorarium
Merck: Investigator and Scientific Advisor , Consulting fee and Research grant
Janssen: Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Research grant and Speaker honorarium

P. Kwo, Gilead: Grant Investigator and Scientific Advisor , Research grant and Salary
Abbvie: Grant Investigator and Scientific Advisor , Research grant and Salary
BMS: Grant Investigator and Scientific Advisor , Research grant and Salary
Janssen: Grant Investigator and Scientific Advisor , Research grant and Salary
Merck: Grant Investigator and Scientific Advisor , Research grant and Salary

M. Ngyuyen, Gilead: Consultant , Grant Investigator and Investigator , Consulting fee , Grant recipient and Research grant

J. C. Yang, Gilead Sciences: Employee , Salary

L. Stamm, Gilead Sciences: Employee , Salary

S. Lu, Gilead Sciences: Employee , Salary

H. Sobol, Gilead Sciences: Employee , Salary

S. Naik, Gilead: Employee , Salary

J. Llewellyn, Gilead Sciences: Employee , Salary

D. Brainard, Gilead Sciences: Employee , Salary

J. G. Mchutchison, Gilead Sciences: Employee , Salary

M. Curry, Gilead Sciences: Research Contractor , Research grant
Abbvie: Scientific Advisor , Salary
Bristol Myers Squibb: Scientific Advisor , Salary
Conatus: Research Contractor , Research support

K. Kowdley, AbbVie: Research Contractor and Scientific Advisor , Consulting fee and Research support
Gilead: Consultant , Research Contractor and Scientific Advisor , Consulting fee , Research support and Speaker honorarium
Merck: Research Contractor , Research support
Trio Health: Board Member , Consulting fee

N. Reau, Gilead: Investigator and Scientific Advisor , Consulting fee
AbbVie: Investigator and Scientific Advisor , Consulting fee
Merck: Scientific Advisor , Consulting fee
BMS: Scientific Advisor , Consulting fee

E. Gane, Gilead Sciences: Scientific Advisor and Speaker's Bureau , Consulting fee and Speaker honorarium
Merck: Scientific Advisor and Speaker's Bureau , Consulting fee and Speaker honorarium
AbbVie: Scientific Advisor and Speaker's Bureau , Consulting fee and Speaker honorarium
Janssen: Scientific Advisor , Consulting fee

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