Efficacy and safety of glecaprevir/pibrentasvir in HCV-infected Japanese patients with prior DAA experience, severe renal impairment, or genotype 3 infection.

Abstract

BACKGROUND:

Once-daily, orally administered, co-formulated glecaprevir (NS3/4A protease inhibitor) and pibrentasvir (NS5A inhibitor) (G/P) demonstrated pangenotypic activity and high sustained virologic response (SVR) rates in studies outside Japan. Here we report safety and efficacy in a subset of Japanese patients with chronic HCV infection who received G/P 300/120 mg in a phase 3, open-label, multicenter study (CERTAIN-1).

METHODS:

This analysis focuses on three difficult-to-treat subgroups: HCV GT1/2-infected patients who failed to achieve SVR after treatment with a direct acting antiviral (DAA)-containing regimen; GT1/2-infected patients with severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73 m2); and GT3-infected patients. Patients in the renal impairment and GT3 cohorts were treatment-naive or interferon treatment-experienced. Noncirrhotic GT1/2-infected, DAA-naïve patients in the renal impairment cohort received G/P for 8 weeks; all other patients were treated for 12 weeks. Primary outcome was SVR (HCV RNA < 15 IU/mL) 12 weeks post-treatment (SVR12).

RESULTS:

The study enrolled 33 GT1/2-infected patients who failed previous DAA treatment (four with cirrhosis); 12 GT1/2-infected patients with severe renal impairment (two with cirrhosis); and 12 GT3-infected patients (two with cirrhosis). SVR12 was achieved by 31/33 (93.9%), 12/12 (100%), and 10/12 (83.3%) patients, respectively. One serious adverse event (fluid overload, not related to G/P) occurred in a patient on chronic intermittent hemodialysis.

CONCLUSIONS:

G/P achieved high SVR12 rates and was well tolerated in three difficult-to-treat patient subgroups with limited treatment options in Japan (DAA-experienced patients, patients with severe renal impairment, and GT3-infected patients). These results support the potential suitability of this regimen for these special populations in Japan.

• Authors: Hiromitsu Kumada, Tsunamasa Watanabe, Fumitaka Suzuki, Kenji Ikeda, Ken Sato, Hidenori Toyoda, Masanori Atsukawa, Akio Ido, Akinobu Takaki, Nobuyuki Enomoto, Koji Kato, Katia Alves, Margaret Burroughs, Rebecca Redman, David Pugatch, Tami J Pilot-Matias, Preethi Krishnan, Rajneet K Oberoi, Wangang Xie, Kazuaki Chayama
• Journal: Journal of gastroenterology (J Gastroenterol) Vol. 53 Issue 4 Pg. 566-575 (Apr 2018) ISSN: 1435-5922 [Electronic] Japan
• PMID: 29052790 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study)

Chemical References

• Aminoisobutyric Acids
• Antiviral Agents
• Benzimidazoles
• Cyclopropanes
• Lactams, Macrocyclic
• Pyrrolidines
• Quinoxalines
• RNA, Viral
• Sulfonamides
• pibrentasvir
• Proline
• Leucine
• glecaprevir

Topics

• Adolescent
• Adult
• Aged
• Aminoisobutyric Acids
• Antiviral Agents (adverse effects, therapeutic use)
• Benzimidazoles (adverse effects, therapeutic use)
• Cyclopropanes
• Drug Therapy, Combination
• Female
• Genotype
• Hepacivirus (genetics, isolation & purification)
• Hepatitis C, Chronic (complications, drug therapy, virology)
• Humans
• Lactams, Macrocyclic
• Leucine (analogs & derivatives)
• Male
• Middle Aged
• Proline (analogs & derivatives)
• Pyrrolidines
• Quinoxalines (adverse effects, therapeutic use)
• RNA, Viral (blood)
• Renal Insufficiency (complications)
• Sulfonamides (adverse effects, therapeutic use)
• Sustained Virologic Response
• Treatment Failure
• Treatment Outcome
• Young Adult