The combination of direct-acting antiviral agents glecaprevir/pibrentasvir (G/P), sofosbuvir, and ribavirin is now approved for new patient populations.
The next-generation fixed-dose combination therapy of glecaprevir/pibrentasvir (Mavyret (G/P)) was approved by the US Food and Drug Administration (FDA) in August 2017 for the treatment of chronic hepatitis C virus (HCV) genotypes 1-6 without cirrhosis or with mild cirrhosis, including patients with moderate to severe kidney disease and those who are on dialysis. The combo was also approved for adult patients with HCV genotype 1 infection who had been previously treated with a regimen either containing an NS5A inhibitor or an NS3/4A protease inhibitor, but not both.
This week, the FDA approved revisions to the drug’s label to include dosing recommendations for individuals who have undergone liver or kidney transplants, those who are treatment-naïve or PRS treatment-experienced adults with HCV/HIV-1 coinfection without cirrhosis or with compensated cirrhosis, as well as treatment-naïve or PRS treatment-experienced adults with liver or kidney transplant without cirrhosis. (PRS indicates prior treatment experience with regimens containing interferon, pegylated interferon, ribavirin, and/or sofosbuvir, but no prior treatment experience with an HCV NS3/4A PI or NS5A inhibitor.)
This update to the drug’s label was based on safety and efficacy data gleaned from the HCV/HIV-1 coinfection study (M14-730) and the live and renal transplant study (M13-596).
Research has shown that G/P has demonstrated high sustained virologic response (SVR) in patients regardless of HCV genotype or baseline patient or viral characteristics; however, about 1% of patients treated in the G/P clinical trial program to-date have had virologic failure (VF). Those patients were enrolled in the MAGELLAN-3 (NCT02939989) retreatment study, which is “an ongoing phase 3b, open-label trial, in which patients who had VF following G/P are retreated with the combination of G/P 300 mg/120 mg once daily (QD) + sofosbuvir (SOF) 400 mg QD + ribavirin (RBV) 1000—1200 mg (weight based, twice daily).”
The outcomes of this research at weeks 4 and 12 post-treatment were presented at the 25th Conference on Retroviruses and Opportunistic Infections (CROI) in Boston, Massachusetts.
A total of 24 participants (19 male; 5 female) were distributed into 2 arms, A and B. Those patients (3) who “were non-GT3- infected, non-cirrhotic, and naïve to protease inhibitor and/or NS5A inhibitor prior to VF with the G/P regimen [were placed into Arm A],” according to the investigators. These patients received 12-weeks of treatment with the study combination regimen. Arm B participants—all other patients (21) who did not meet the criteria for Arm A—received the combination regimen for 16 weeks.
Further patient characteristics for Arm A include:
Patient characteristics for Arm B:
The primary outcome of the trial is SVR at post-treatment (PT) Week 12 [SVR12]. Baseline resistance and safety were also assessed. All patients continued with the trial to 12 weeks and “no significant laboratory abnormalities were observed,” according to the study authors.
Dr. Wyles discussed the results of the trial at 4 and 12 weeks post-treatment (see video, below).
The retreatment regimen was found to be well-tolerated, with about 10% of the study participants reporting adverse events (AEs). Chief among these were headache (25.0%) and pruritus (25.0%), followed by dizziness (16.7%) and irritability (16.7%). One participant had a serious AE (cholelithiasis); however, the study investigators deemed this to be unrelated to the treatment regimen.
Based on the results of the study, Dr. Wyles had the following to share moving forward (see video).