Retreatment of patients who failed glecaprevir/pibrentasvir treatment for hepatitis C virus infection.
Wyles D, Weiland O, Yao B, Reindollar R, Weilert F, Dufour JF, Gordon SC, Poordad F, Stoehr A, Brown A, Mauss S, Samanta S, Pilot-Matias T, Jr LR, and Trinh R. Retreatment of patients who failed glecaprevir/pibrentasvir treatment for hepatitis C virus infection. J Hepatol 2018; 68:S23-S24.
Background and Aims: Glecaprevir/pibrentasvir (G/P; glecaprevir identified by AbbVie and Enanta) has demonstrated high rates of sustained virologic response at posttreatment week 12 (SVR12) across all six major hepatitis C virus (HCV) genotypes (GT). Roughly 1% of patients treated with G/P in Phase II or III clinical trials, across all genotypes, had virologic failure. These patients were offered enrollment into a retreatment study, MAGELLAN-3. Method: MAGELLAN-3 is an ongoing open-label, phase 3b trial to determine the efficacy and safety of G/P (300/120 mg once daily) + sofosbuvir (SOF; 400 mg once daily) + ribavirin (RBV; 1,000- 1,200 mg daily, divided into two doses) in patients who had virologic failure on G/P treatment in an AbbVie-sponsored clinical trial. Patients who had non-GT 3 infection, without cirrhosis, and were naïve to NS3/4A protease and NS5A inhibitors prior to failure with G/ P, received 12 weeks of treatment; all others received 16 weeks. Efficacy (percentage of patients with SVR12), safety, and baseline resistance were assessed. Patients with at least end-of-treatment (EOT) data are reported here. Results: Of 23 patients enrolled, 19 reached EOT; 2 patients were treated for 12 weeks (both reached EOT) and 21 were treated for 16 weeks (17 reached EOT). Overall, 30% (7/23), 9% (2/23), and 61% (14/ 23) of patients had HCV GT 1, 2, and 3 infection, respectively, and 30% (7/23) of patients had compensated cirrhosis. Twenty six percent (6/ 23) of patients had NS3/4A protease and/or NS5A inhibitor experience prior to their original G/P treatment; 39% (9/23) of patients had prior experience to other HCV treatment regimens. Twenty two percent (5/23) of patients had baseline resistanceassociated substitutions (RAS) in NS3; the most common were at position D/Q168 (n = 4). All 23 patients had baseline RAS in NS5A (14 had multiple NS5A RAS); the most commonwere at position Q30 (n = 6) in GT1, and Y93 (n = 11) and A30 (n = 9) in GT3. One patient had virologic failure; currently available SVR12 rates are shown in the Figure. The retreatment regimen was well tolerated. One patient had a serious adverse event of cholelithiasis at treatment week 10. Complete efficacy and safety data will be presented at the conference. Conclusion: Preliminary data show that retreatment with G/P + SOF + RBV for 12 or 16 weeks was well tolerated and has demonstrated a high rate of SVR12, regardless of HCV genotype or baseline resistance-associated substitutions. (Figure presented) .