During this year’s edition of Digestive Diseases Week (DDW), researchers presented exciting pooled clinical data supporting the use of 2 investigational direct-acting antiviral (DAA) regimens, AbbVie’s glecaprevir/pibrentasvir (G/P) and Gilead’s sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX), for the treatment of hepatitis C patients who have chronic kidney disease (CKD) or who have previously failed DAA therapy, respectively.
A once-daily, all-oral regimen, AbbVie’s G/P consists of a pangenotypic NS3/4A inhibitor (glecaprevir, G) and a pangenotypic NS5A inhibitor (pibrentasvir, P), both of which primarily undergo biliary excretion—making them a potentially attractive option for treating hepatitis C patients with renal impairment. Researchers at DDW presented an integrated analysis of the safety and efficacy of G/P in 2,169 hepatitis C patients with all stages of CKD across a large number of Phase II and Phase III studies (ENDURANCE-1, -2, -3, and -4; EXPEDITION-1 and -4; SURVEYOR-1 and -2).
Overall, these pooled data show that a 12-week regimen of G/P is highly efficacious regardless of CKD stage, with sustained virologic response (SVR) rates of 98.3% (stage 1 CKD; N=633), 98.0% (stage 2 CKD; N=593), 100.0% (stage 3 CKD; N=18), and 98.1% (stage 4/5 CKD; N=103). Serious adverse events (SAEs) were rare among all patients, and dialysis was not associated with treatment failure or an increased frequency of AEs or SAEs. GlobalData believes these data will position G/P for solid uptake in this patient population once it receives approval.
Gilead’s once-daily regimen, SOF/VEL/VOX, combines the components of Epclusa (sofosbuvir, SOF/velpatasvir, VEL) with the company’s investigational NS3/4A inhibitor (voxilaprevir, VOX). Researchers at DDW presented an integrated resistance analysis of the safety and efficacy of SOF/VEL/VOX as a function of baseline resistance-associated substitutions (RAS) in over 430 DAA-experienced patients enrolled in the POLARIS-1 and -4 studies. The most frequently observed baseline RAS in the study participants were NS5A, and NS3 RAS were also common amongst these patients.
Overall, these data demonstrated that baseline RAS did not impact the efficacy and safety of a 12-week regimen of SOF/VEL/VOX, with high SVR rates achieved in patients with NS5A position Y93 RAS (95%) and patients with ≥2 NS5A RAS (100%) from the POLARIS-1 study. Importantly, any observed viral relapse was not associated with emergence of viral resistance. Because experts at DDW cited persistent NS5A RAS as a key remaining concern in the treatment of hepatitis C, GlobalData believes that SOF/VEL/VOX will be well-positioned for use as a salvage therapy in patients who have previously failed DAA therapy, particularly an NS5A-containing regimen.
Based on the integrated analyses presented at DDW, GlobalData expects AbbVie’s G/P to quickly become a preferred option for treating patients with CKD, regardless of the extent of renal impairment. Similarly, Gilead’s SOF/VEL/VOX should be welcomed by clinicians as a reliable salvage regimen for treating DAA-experienced patients independent of baseline RAS. While minor gaps in the treatment landscape still remain, these data bring the medical community one step closer to being able to cure all hepatitis C patients.