Treatment-Naive Genotype 2 Without Cirrhosis

Recommended regimens listed by evidence level and alphabetically for:

Treatment-Naive Genotype 2 Patients Without Cirrhosis

RECOMMENDED DURATION RATING
Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)a 8 weeks I, A
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) 12 weeks I, A
a Dosing is 3 coformulated tablets (glecaprevir [100 mg]/pibrentasvir [40 mg]) taken once daily. Please refer to the prescribing information.

 

Recommended Regimens

Glecaprevir/Pibrentasvir

ENDURANCE-2 was a randomized, double-blind, placebo-controlled trial of the daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg) administered as three 100 mg/40 mg fixed-dose combination pills for 12 weeks among 302 genotype 2-infected treatment-naive or -experienced participants. Treatment-experienced patients included those previously treated with interferon or peginterferon ± ribavirin, or sofosbuvir plus ribavirin ± peginterferon. Patients randomized to placebo later received open-label treatment with glecaprevir/pibrentasvir for 12 weeks. Among 202 patients randomized to active treatment, 70% (141/202) were treatment naive and none had cirrhosis. The SVR12 rates were 99% and 100% by intention-to-treat and modified intention-to-treat analysis, respectively. There were no virologic failures. One participant who achieved SVR4 was lost to follow-up before the SVR12 evaluation. There was no effect of baseline RASs on SVR12 rate. Overall, therapy was well tolerated and the adverse event profile was not different compared to placebo (Asselah, 2018b).

A shorter duration of glecaprevir/pibrentasvir for 8 weeks was evaluated in the SURVEYOR-II, part 4 study. This was a single-arm, phase 2 study that evaluated glecaprevir/pibrentasvir for 8 weeks among 203 treatment-naive or -experienced patients (previously treated with interferon or peginterferon ± ribavirin, or sofosbuvir plus ribavirin ± peginterferon) with genotype 2, 4, 5, or 6 infection without cirrhosis. Of the 142 genotype 2-infected patients, 137 (96%) were treatment naive. Among the treatment-naive, genotype 2-infected participants, 135/137 (99%) achieved SVR12. The presence of baseline RASs had minimal effect on SVR12 rates. Fifty-three of 126 (42%) treatment-naive and -experienced participants with genotype 2 had the L31M RAS within the NS5A gene at baseline. Fifty-one of 53 (96%) of these participants achieved SVR12 (Asselah, 2018b).

While not a head-to-head comparison, the results of ENDURANCE-2 and SURVEYOR-II, part 4 indicate that glecaprevir/pibrentasvir administered for 8 or 12 weeks is highly efficacious among genotype 2-infected, treatment-naive patients without cirrhosis. In an integrated analysis of 297 DAA-naive, noncirrhotic patients with genotype 2 infection treated with 8 weeks of glecaprevir/pibrentasvir in 6 phase 2 or 3 clinical trials, SVR12 was 98% (252/257) (Naganuma, 2019). Additionally, a real-world cohort of treatment-naive, noncirrhotic genotype 2 patients from Italy treated with glecaprevir/pibrentasvir for 8 weeks achieved an SVR rate of 98% (173/175) (D’Ambrosio, 2019).

Sofosbuvir/Velpatasvir

The daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) for 12 weeks was approved by the FDA for the treatment of genotype 2 infection in patients without cirrhosis or with compensated cirrhosis. ASTRAL-2 compared 12 weeks of sofosbuvir/velpatasvir to 12 weeks of sofosbuvir plus ribavirin in 266 treatment-naive and -experienced patients without cirrhosis or with compensated cirrhosis. The study showed superior efficacy of sofosbuvir/velpatasvir (SVR12 99% vs 94%); (Foster, 2015a). ASTRAL-1 also included 104 genotype 2 treatment-naive and -experienced participants without cirrhosis or with compensated cirrhosis, all of whom achieved SVR12 (Feld, 2015). Pooled analysis of all genotype 2 patients in ASTRAL-1 and ASTRAL-2 demonstrated 100% SVR12 in participants with compensated cirrhosis (29/29) and 99% SVR12 in treatment-naive participants (194/195). Among patients with genotype 2 receiving sofosbuvir/velpatasvir, the presence of baseline NS5A or NS5B RASs was not associated with virologic failure (Asselah, 2018).

The POLARIS-2 phase 3 study randomized DAA-naive patients to 8 weeks of sofosbuvir (400 mg)/velpatasvir (100 mg)/voxilaprevir (100mg) versus 12 weeks of sofosbuvir/velpatasvir. Fifty-three patients with genotype 2 were included in the sofosbuvir/velpatasvir arm and all achieved SVR12 (100%). This study confirms the high efficacy and safety of this 12-week regimen in patients with genotype 2 infection (Jacobson, 2017).

In a single-arm, phase 3 study from Asia that included 375 treatment-naive and -experienced patients with genotype 1, 2, 3, 4, 5, or 6 infection (18% with cirrhosis) treated with 12 weeks of sofosbuvir/velpatasvir, SVR was achieved in 95% (362/375) (Wei, 2019). Of the 62 patients with genotype 2 infection, 100% achieved SVR.

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Last update: 
November 6, 2019
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