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).

• Authors: Atsushi Naganuma, Kazuaki Chayama, Kazuo Notsumata, Edward Gane, Graham R Foster, David Wyles, Paul Kwo, Eric Crown, Abhi Bhagat, Federico J Mensa, Tetsuya Otani, Lois Larsen, Margaret Burroughs, Hiromitsu Kumada
• Journal: Journal of gastroenterology (J Gastroenterol) Vol. 54 Issue 8 Pg. 752-761 (Aug 2019) ISSN: 1435-5922 [Electronic] Japan
• PMID: 30868245 (Publication Type: Journal Article)

Chemical References

• Antiviral Agents
• Benzimidazoles
• Drug Combinations
• Pyrrolidines
• Quinoxalines
• Sulfonamides
• glecaprevir and pibrentasvir

Topics

• Adult
• Aged
• Aged, 80 and over
• Antiviral Agents (administration & dosage, adverse effects)
• Benzimidazoles (administration & dosage, adverse effects)
• Clinical Trials, Phase II as Topic
• Clinical Trials, Phase III as Topic
• Drug Combinations
• Female
• Genotype
• Hepacivirus (genetics, isolation & purification)
• Hepatitis C, Chronic (drug therapy, virology)
• Humans
• Japan
• Male
• Middle Aged
• Pyrrolidines (administration & dosage, adverse effects)
• Quinoxalines (administration & dosage, adverse effects)
• Retrospective Studies
• Sulfonamides (administration & dosage, adverse effects)
• Sustained Virologic Response
• Young Adult