Although direct-acting antiviral ( DAA ) therapies for chronic hepatitis C virus ( HCV ) infection have demonstrated high rates of sustained virologic response, virologic failure may still occur, potentially leading to the emergence of viral resistance, which can decrease the effectiveness of subsequent treatment.
Treatment options for patients who failed previous DAA-containing regimens, particularly those with NS5A inhibitors, are limited, and remain an area of unmet medical need.
MAGELLAN-1, a phase 2, open-label study, has evaluated the efficacy and safety of Glecaprevir ( GLE ) + Pibrentasvir ( PIB ) ± Ribavirin ( RBV ) in HCV genotype 1-infected patients with prior virologic failure to HCV DAA-containing therapy.
A total of 50 non-cirrhotic patients were randomized to three arms: 200 mg Glecaprevir + 80 mg Pibrentasvir ( Arm A ), 300 mg Glecaprevir + 120 mg Pibrentasvir with 800 mg once-daily Ribavirin ( Arm B ), or 300 mg Glecaprevir + 120 mg Pibrentasvir without Ribavirin ( Arm C ).
By intent-to-treat analysis, sustained virologic response at post-treatment week 12 ( SVR12 ) was achieved in 100% ( 6/6, 95% CI 61 – 100 ), 95% ( 21/22, 95% CI 78-99 ), and 86% ( 19/22, 95% CI 67- 95 ) of patients in Arms A, B, and C, respectively.
Virologic failure occurred in no patients in Arm A, and 1 patient each in Arms B and C ( two patients lost to follow-up in Arm C ).
The majority of adverse events were mild in severity; no serious adverse events related to study drug and no relevant laboratory abnormalities in alanine aminotransferase, total bilirubin, or hemoglobin, were observed.
In conclusion, the combination of Glecaprevir and Pibrentasvir was highly efficacious and well-tolerated in patients with HCV GT1 infection and prior failure to DAA-containing therapy; Ribavirin coadministration did not improve efficacy. ( Xagena )
Poordad F et al, Hepatology 2017; Epub ahead of print