GI-5005 Therapeutic Vaccine Plus Peg-IFN/Ribavirin Improves Sustained Virologic Response Versus Peg-IFN/Ribavirin In Prior Non-Responders With Genotype 1 Chronic HCV Infection
P. Pockros; I. Jacobson; T. D. Boyer; E. R. Schiff; G. T. Everson; W. M. Lee; J. M. Vierling; E. Lawitz; M. Kugelmas; N. Tsai; M. L. Shiffman; R. S. Brown; B. R. Armstrong; A. Mattson; T. C. Rodell; D. Apelian
Background and aims: The GI-5005 therapeutic vaccine has been shown to improve sustained virologic response in naïve subjects with the greatest effect observed in IL28B T/T subjects. We now report the sustained virologic response (SVR) data from prior IFN/ribavirin non-responders (NR).
Methods: HCV genotype 1 patients were randomized 1:1, and stratified by prior treatment status; Arm 1- GI-5005 monotherapy run-in of five weekly followed by 2 monthly subcutaneous (SC) doses of 40YU (1 YU = 10 yeast) GI-5005 over 12 weeks, followed by triple therapy of monthly 40YU GI-5005 doses plus 48 weeks pegIFN α-2a/ribavirin (SOC), Arm 2- SOC alone. NRs received 72 weeks of triple therapy versus SOC. Prior NRs were defined as poor responders (> 1 log10 and < 2 log10 reduction) or partial responders (> 2 log10 reduction without clearance at any time during therapy). Prior null response, relapse, and breakthrough were exclusionary.
Results: Triple therapy was well tolerated with an equivalent number of discontinuations due to adverse events in each group; Triple 8/68(11.8%) and SOC 8/65(12.3%). Improvement in end of treatment response (ETR) (Triple 6/18 [33%] vs SOC 2/19 [11%]) and SVR (Triple 3/18[17%] vs SOC 1/19[5%]) was observed in NR patients. Due to the small number of patients in each treatment arm, these differences were not statistically significant (see table). SVR in NRs occurred only in IL28B C/T subjects (Triple 3/13[23%] vs SOC 1/13[8%]). In summary, GI-5005 triple therapy delivered improved ETR and SVR (Δ ranging from 10-22%) in all patient subgroups (see table).
Conclusions: GI-5005 plus SOC is well tolerated and improved SVR rates compared to SOC in genotype 1 NR patients. ETR and SVR rates were improved by GI-5005 triple therapy for all subgroups (all, naïve, and NR). These data support further investigation of GI-5005 triple therapy in naïve and NR patients as well as novel combination strategies for GI-5005 with other HCV inhibitory agents in larger numbers of patients.