Integrated analysis of 8-week glecaprevir/pibrentasvir in Japanese and overseas patients without cirrhosis and with hepatitis C virus genotype 1 or 2 infection

Abstract

Background: Chronic hepatitis C virus (HCV) infection with genotypes (GT) 1 and 2 accounts for over 50% of HCV infections globally, including over 97% of all HCV infections in Japan. Here, we report an integrated analysis of efficacy and safety of 8-week treatment with the all-oral, fixed-dose combination of the direct acting antivirals (DAA), glecaprevir and pibrentasvir (G/P), in DAA-naïve Japanese and overseas patients without cirrhosis and with HCV GT1 or GT2 infection.

Methods: Data from 899 DAA-naïve patients without cirrhosis and with HCV GT1 or GT2 infection treated with G/P (300/120 mg) for 8 weeks in the six Phase 2 or 3 overseas or Japan-only clinical trials were included. All patients who received ≥ 1 dose of G/P were included in an intent-to-treat (ITT) analysis. The objectives were to evaluate rate of sustained virologic response 12 weeks post-treatment (SVR12) and safety of the 8-week regimen in the ITT population.

Results: Overall, SVR12 was achieved by 98.9% (889/899) of DAA-naïve patients without cirrhosis, including 99.2% (597/602) of GT1-infected and 98.3% (292/297) of GT2-infected patients. Less than 1% (2/899) of patients overall and no Japanese patients experienced virologic failure. SVR12 rate was > 97% for patients regardless of baseline characteristics, and common comorbidities or co-medications. Overall, < 1% (2/899) discontinued G/P due to an adverse event (AE) and 1.6% (14/899) of patients experienced a serious AE.

Conclusions: 8-week G/P treatment is safe and efficacious in DAA-naive patients without cirrhosis and with HCV GT1 or GT2 infection, demonstrating high SVR12 rates regardless of baseline patient and disease characteristics. CLINICALTRIALS.

Gov identifiers: The trials discussed in this paper were registered with ClinicalTrials.gov as follows: NCT02707952 (CERTAIN-1), NCT02723084 (CERTAIN-2), NCT02243280 (SURVEYOR-I), NCT02243293 (SURVEYOR-II), NCT02604017 (ENDURANCE-1), NCT02738138 (EXPEDITION-2).

Keywords: Antiviral agents; Chronic hepatitis C; Comorbidity; Protease inhibitors; Sustained virologic response.

Conflict of interest statement

Atsushi Naganuma and Kazuo Notsumata have nothing to disclose. Kazuaki Chayama received research funding from AbbVie, Bristol-Myers Squibb, Dainippon Sumitomo Pharma, Toray Industries, Inc. and received payment for lectures from AbbVie, Bristol-Myers Squibb, Gilead, and MSD. Edward Gane is an advisor for AbbVie, Alnylam, Arbutus, Assembly, Arrowhead, Enanta, Gilead Sciences, Janssen, Merck, Novartis, Novira, Roche, and VIR, and participated in speakers’ bureaus for AbbVie, Gilead Sciences. Graham Foster received grants from AbbVie, Gilead, and Merck, and consulted and participated in speakers’ bureaus for AbbVie, MSD, and Gilead. David Wyles received research funding (paid to his institution) from AbbVie, Gilead and Merck, and served as consultant to AbbVie, Gilead and Merck. Paul Kwo participated on advisory committees or review panels for AbbVie, Abbott, Merck, Gilead, Bristol-Meyers Squibb, Janssen, Alnylam, and Inovio, and received grant/research support from AbbVie, Merck, Bristol-Meyers Squibb, Janssen, Gilead, Merck, and Conatus. Eric Crown, Abhi Bhagat, Margaret Burroughs, Federico Mensa, Tetsuya Otani, and Lois Larsen are employees and may hold stock or options. Hiromitsu Kumada received payment for lectures from AbbVie GK, MSD, Dainippon Sumitomo Pharma, Bristol-Myers Squibb, and Gilead.

Figures

Fig. 1

Overall SVR12 comparing Japan and overseas rates by genotype. Efficacy of 8-week G/P treatment defined as SVR12 is reported for both Japan and overseas patients by genotype using an ITT analysis. The table lists the reason for non-response including virologic (breakthrough or relapse) and non-virologic failure (premature discontinuation or missing SVR12) for each group. Premature d/c, Premature discontinuation

Fig. 2

SVR12 by baseline patient and disease characteristics. Efficacy of 8-week G/P treatment reported by baseline patient (a) and disease (b) characteristics using an ITT analysis. The dashed line represents the overall SVR12 for 899 patients included in the analysis. aAll patients with missing data for baseline polymorphisms achieved SVR12. bDefined as having any baseline NS3 resistance-associated variant (at amino acid positions 155, 156, and 168) at ≥ 15% NGS detection threshold. cDefined as having any baseline NS5A resistance-associated variant (at amino acid positions 24, 28, 30, 92, and 93) at ≥ 15% NGS detection threshold

Fig. 3

SVR12 by comorbidities and co-medications. Efficacy of 8-week G/P treatment, defined as SVR12, is reported by comorbidity (a–b) and co-medications (c) using an ITT analysis. GERD, gastroesophageal reflux disease; CKD, chronic kidney disease; CCB calcium channel blockers, ARB angiotensin receptor blockers, PPI proton-pump inhibitors