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).
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.
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.
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.