vedroprevir (GS 9451) / Gilead - LARVOL DELTA

GS-5885, GS-9451 with peginterferon alfa 2a (PEG) and ribavirin in treatment-naïve subjects with chronic genotype 1 hep C virus infection and IL28B CC genotype (clinicaltrials.gov) - P2, N=235; Recruiting; Completion date: Apr 2014 -> Mar 2015

Completion date • Trial delayed • Hepatitis C Virus

GS 5885 administered concomitantly with GS-9451, tegobuvir and ribavirin (RBV) in chronic genotype 1 hepatitis C Virus (HCV) infection (clinicaltrials.gov) - P2, N=120; Recruiting -> Active, not recruiting

Enrollment closed • Hepatitis C Virus

Pill burden & treatment length reduce adherence to IFN-free hepatitis C therapy in an urban cohort (CROI 2014) - Abstract #667; P2, N=60; SYNERGY (NCT01805882); "Adherence to short courses of DAA therapy with 1-3 pills once a day was excellent in an urban population with multiple risk factors for non-adherence. Increased pill burden and duration of treatment decreased adherence."

P2 data • Hepatitis C Virus

[Late breaking abstract] Combination oral, hepatitis C antiviral therapy for 6 or 12 weeks: Final results of the SYNERGY trial (CROI 2014) - Abstract #27LB; P2, N=60; SYNERGY (NCT01805882); "The end of treatment response (HCV RNA <LLOQ) was 100%, 75% and 95% of subjects in Arms A, B and C respectively using a more sensitive HCV assay with lower limit of quantification of 12 IU/mL (Fig 1). Using an HCV RNA assay with a lower limit of quantification of <43 IU/mL 100% of patients on all arms were suppressed at EOT. 100%, 90% and 95% of patients in Arm A, B and C respectively achieved SVR12." 

P2 data • Hepatitis C Virus

All-oral combination of ledipasvir, vedroprevir, tegobuvir, and ribavirin in treatment-naive patients with genotype 1 HCV infection (Hepatology) - P2, N=140; NCT01353248; Sponsor: Gilead; "Sustained virologic response 12 weeks after treatment (SVR12) was higher in patients receiving 90 mg LDV for 24 weeks (63%) compared to LDV 90 mg for 12 weeks (54%) and LDV 30 mg for 24 weeks (48%). In patients with vRVR in Arm 2, SVR12 was achieved by 68% and 81% of patients treated for 12 and 24 weeks, respectively."

P2 data • Hepatitis C Virus

Combination of the NS5A inhibitor, GS-5885, the NS3 protease inhibitor, GS-9451, and pegylated interferon plus ribavirin in treatment experienced patients with genotype 1 hepatitis C infection (EASL 2013) - Presentation time: 25.04.2013, 16:00-18:00; Abstract 13; P2, N=163; NCT01353248; Sponsor: Gilead; “The overall SVR4 response rate was 74%...Higher rates of SVR were observed in patients infected with genotype 1b (97%), those with IL28B CC genotype (100%), and in prior relapsers (93%).”

P2 data • Hepatitis C Virus

High sustained virologic response rate in treatment-naïve HCV genotype 1A and 1B patients treated for 12 weeks with an interferon-free all-oral quad regimen: Interim results (EASL 2012) - Presentation time: 19.04.2012, 09:00-18:00; P2, N=141; 26 of 27 (96%) achieved SVR4; Viral breakthrough occurred only in GT1a patients (8/55); Two patients terminated early; IL28B status did not appear to correlate with SVR4 or breakthrough

P2 interim data • Hepatitis C Virus

Ledipasvir + GS-9451 + peginterferon and ribavrin (PR) for six or 12 weeks achieves a high SVR12 in treatment naïve genotype 1 IL28B CC patients (AGW 2013) - P2, N=244; NCT01384383; Sponsor: Gilead Sciences; "These data demonstrate a high SVR12 (82–100%) with 6 or 12 wks of two direct-acting antivirals plus PR result in high rates of response in a treatment naïve, non-cirrhotic, IL28 CC population. Additionally, 12 wks of the 4 drug regimen is comparable to 24 wks of PR."

P2 data • Hepatitis C Virus

Effect of early viral kinetics on Interferon-g inducible protein-10 in patients given an all-oral anti-hepatitis C virus regimen (CROI 2013) - Abstract#703; Sponsor: Gilead; P2, N=124; NCT01353248; "All patients receiving anti-viral therapy had a rapid decline in HCV RNA, but overall response varied. Over the first 2 weeks of treatment, a bi-phasic pattern of IP-10 decline was observed"

P2 data • Hepatitis C Virus

Antiviral efficacy of the NS3 protease inhibitor, GS-9451, non-nucleoside NS5B inhibitor, tegobuvir, and pegylated interferon plus ribavirin in treatment-naïve genotype 1 hepatitis C infected patients (EASL 2013) - Presentation time: 26.04.2013, 16:00-18:00; Abstract 68; P2, N=239; NCT01353248; Sponsor: Gilead; “The regimen was well tolerated with 4-6% of patients experiencing a serious adverse event…addition of GS-9451 to a PEG/RBV regimen results in improved SVR12 rates in treatment-naïve, genotype 1 HCV patients relative to PEG/RBV.”

P2 data • Hepatitis C Virus

The paradox of highly effective sofosbuvir-based combination therapy despite slow viral decline: can we still rely on viral kinetics? (PubMed, Sci Rep) - "High sustained virologic response (SVR) rates have been observed after 6 weeks of anti-HCV treatment using sofosbuvir, ledipasvir and a non-nucleoside polymerase-inhibitor (GS-9669) or a protease-inhibitor (GS-9451) and after 12 weeks with sofosbuvir + ledipasvir. In conclusion, the rapid cure rate achieved with these combinations is largely disconnected from viral loads measured during treatment. A model assuming that rapid cure is due to a drug effect of generating non-infectious virus could be a basis for future response guided therapy."

Combination therapy • Journal