Retreatment of hepatitis C infection in patients who failed glecaprevir/pibrentasvir.
Wyles DL, Weiland O, Yao B, Reindollar R, Weilert F, Dufour JF, Gordon S, Poordad F, Stoehr A, Brown A, Mauss S, Samanta S, Pilot-Matias T, Rodrigues L, and Trinh R. Retreatment of hepatitis C infection in patients who failed glecaprevir/pibrentasvir. Top Antivir Med 2018; 26:51s-52s.
Top Antivir Med
Background: Glecaprevir∗/pibrentasvir (G/P;∗identified by AbbVie and Enanta) is a next-generation Hepatitis C virus (HCV) treatment regimen that has demonstrated high sustained virologic response (SVR) regardless of HCV genotype (GT) or baseline patient or viral characteristics. Approximately 1% of patients treated in the G/P clinical trial program to date had virologic failure (VF) and no data have been presented on their outcomes following retreatment. These patients were enrolled into a retreatment study, MAGELLAN-3 (NCT02939989). Methods: MAGELLAN-3 is an ongoing phase 3b, open-label trial, in which patients who had VF following G/P were retreated with the combination of G/P 300 mg/120 mg once daily (QD) + sofosbuvir (SOF) 400 mg QD + ribavirin (RBV) 1,000-1,200 mg (weight based, twice daily). Patients who were non-GT3-infected, non-cirrhotic, and naïve to protease inhibitor and/or NS5A inhibitor prior to VF with the G/P regimen received 12-week (Arm A) treatment with the combination regimen; all other enrolled patients who did not meet any of these criteria received the same regimen for 16 weeks (Arm B). Efficacy (primary outcome is SVR at post-treatment (PT) Week 12 [SVR12]), safety, and baseline resistance were assessed. Preliminary SVR at PT Week 4 (SVR4) results, safety, and baseline resistance are reported here. Results: As of 15 September 2017, 24 patients were enrolled (3 in Arm A; 21 in Arm B). Baseline characteristics are presented in the table. To date, 12 of 13 patients who completed PT Week 4 achieved SVR4. One patient in Arm B who had a GT1 infection and prior treatment experience with protease inhibitor and/or NS5A inhibitor before failing the G/P regiment experienced relapse at PT Week 4. Adverse events (AEs) reported in ≥10% of patients overall were headache (25.0%), pruritus (25.0%), dizziness (16.7%), and irritability (16.7%). One patient had a serious AE of cholelithiasis considered unrelated to the treatment by the investigator. There were no study discontinuations. No significant laboratory abnormalities were observed. Conclusion: Preliminary data show that the combination of direct-acting antiviral agents G/P + SOF + RBV yielded a high rate of SVR4 in patients who had VF with G/P treatment. The retreatment regimen was well tolerated. Study enrollment is ongoing and updated results, including the SVR12 rate for this subset of patients, will be reported at the conference. (Table Presented).