Sofosbuvir plus seraprevir therapy effective, safe in HCV genotype 1 infection

The combination therapy sofosbuvir-seraprevir appears to be effective and well tolerated in patients with chronic hepatitis C virus (HCV) genotype 1 infection without cirrhosis, results of a phase III trial have shown.

The study was conducted in China by Xiaoyu Wen and colleagues to assess the safety and efficacy of an all-oral interferon-free regimen of seraprevir, an NS3/4A protease inhibitor, and sofosbuvir in HCV patients for 12 weeks. The results were then presented at the recently concluded Digital International Liver Congress (ILC) 2020.

A total of 205 patients (aged 18–75 years) with noncirrhotic, chronic HCV genotype 2 infection were enrolled from 23 sites between 17 October 2018 and 17 January 2019. Of these, 178 (86.8 percent) were HCV treatment-naïve and 27 (13.2 percent) were treatment-experienced. Once-daily sofosbuvir 400 mg plus twice-daily seraprevir 100 mg was administered to patients for 12 weeks.

The primary efficacy endpoint of sustained virological response, defined as HCV RNA <15 IU/mL at 12 weeks after the end of treatment (SVR12), was assessed in all patients who received the study drug. The proportion of adverse events (AEs) resulting in premature discontinuation was the primary safety endpoint.

Of the participants, 203 completed the full treatment course and two discontinued therapy. Majority of the patients were female (54.6 percent), while 2.4 percent had genotype 1a and 97.6 percent had genotype 1b HCV infection. Mean age was 46.9 years (range, 24–73 years. Interferon treatment was administered to 13.2 percent of the participants. [ILC 2020, abstract THU391]

The full analysis set showed a 99.01-percent SVR12 rate, while the overall SVR4 rate was 99.51 percent. One patient relapsed after 4 weeks of follow-up, and another one relapsed after 12 weeks of follow-up.

Upper respiratory tract infection was the most frequent AE, occurring in 32 patients (15.6 percent). One discontinued treatment due to AEs. Eight others (3.9 percent) reported serious AEs, but none was deemed to be associated with the study drug.

“Treatment with ... sofosbuvir-seraprevir was highly effective and well tolerated in genotype 1 chronic HCV-infected population without cirrhosis,” the researchers said.

Previous studies assessing sofosbuvir in combination with other HCV therapy, particularly the HCV NS5A inhibitor velpatasvir and the HCV NS3/4A protease inhibitor voxilaprevir, have shown robust efficacy and high rates of SVR among patients across HCV genotypes in whom treatment with a direct-acting antiviral regimen had previously failed. [N Engl J Med 2017;376:2134-2146; Drugs 2018;78:577-587]

Furthermore, a meta-analysis of randomized controlled trials comparing sofosbuvir and nonsofosbuvir regimens in chronic HCV patients showed that sofosbuvir-treated individuals did not show an increased risk of cardiac outcomes, such as arrhythmia and bradycardia, indicating its relative safety. [Drug Saf 2018;41:77-86]