Once-daily sofosbuvir-velpatasvir regimen effective in Asians with chronic HCV
A once-daily oral dose of sofosbuvir and velpatasvir for 12 weeks leads to sustained virological response (SVR) in a majority of patients with chronic hepatitis C virus (HCV) infection, according to an Asian study. However, the efficacy of this regimen may be reduced in patients with HCV genotype 3b with cirrhosis.
“The study provides additional confirmation of the high efficacy and safety of sofosbuvir-velpatasvir for treatment of patients with HCV infection, but also highlights that patients with HCV genotype 3 or cirrhosis (or both) still have suboptimal results with this drug combination alone,” said Professor David Muljono from the Eijkman Institute for Molecular Biology, Jakarta, Indonesia, in a commentary. [Lancet Gastroenterol Hepatol 2019;4:86-88]
The open-label, phase III trial was conducted in 38 centres in five Asian countries (China, Thailand, Vietnam, Singapore, and Malaysia) and involved 375 adult patients (median age 45 years, 53 percent male, 70 percent Chinese) with chronic HCV genotypes 1–6 (HCV RNA ≥104 IU/mL) who were treated with once-daily doses of the fixed-dose combination tablet containing sofosbuvir (400 mg) and velpatasvir (100 mg) for 12 weeks. The most common HCV genotypes were genotype 1, 6, and 3 at 34, 26, and 22 percent, respectively. Eighty-four patients had HCV genotype 3, 50 percent with genotype 3b, 88 percent of whom were from China.
A majority of the patients were treatment-naïve (82 percent), with 76 percent of patients who had previously received treatment given interferon-based regimens as opposed to direct-acting antivirals.
SVR at 12 weeks after treatment completion or discontinuation (SVR12; HCV RNA <15 IU/mL) was achieved by 97 percent of the patients (n=362), with no incidents of on-treatment virological failure. [Lancet Gastroenterol Hepatol 2019;4:127-134]
SVR12 was achieved by all patients with HCV genotype 1a, 1b, or 2 and by most patients with genotype 6 (99 percent) and genotype 3a (95 percent). However, response rate was lower among patients with HCV genotype 3b at 76 percent.
Among patients with cirrhosis, 90 percent achieved SVR12, with all seven patients with cirrhosis who did not achieve SVR12 having HCV genotype 3b. The likelihood of achieving SVR12 was higher among patients with HCV genotype 3b without cirrhosis compared with patients who had HCV genotype 3b with cirrhosis (89 percent vs 50 percent).
NS5A sequencing data was available for 367 patients; of these, 47 percent had NS5A resistance-associated substitutions at baseline, which was particularly common among patients with HCV genotype 3b (100 percent) and lower among those with HCV genotype 3a (15 percent).
“These overall results support the use of sofosbuvir-velpatasvir in Asian patients with chronic HCV infection, but suggest that those with HCV genotype 3b and cirrhosis might have lower response rates,” said the researchers. However, they acknowledged the over-representation of patients with HCV genotype 3b in this study, which although more common in Asia than in other parts of the world, only represents a small proportion of HCV genotypes in this region.
Fifty percent of patients experienced adverse events (AEs). Upper respiratory tract infection was the most frequently occurring AE (10 percent) followed by headache (5 percent). Three patients experienced serious AEs (one incident each of diabetes-related foot infection, pneumonia, and ligament rupture), though none were deemed treatment-related, and there were no AE-related treatment discontinuations.
Due to the inconsistent availability of HCV genotype testing in Asia coupled with the cost of genotyping and need for laboratory monitoring during treatment, the researchers highlighted the vital role “a single-tablet regimen that is effective at a single duration for all HCV-infected patients, irrespective of genotype or degree of fibrosis” would play in treating patients with HCV, particularly in areas with few resources.
They also highlighted the potential benefit of adding ribavirin to the treatment regimen, which previous studies have shown improved SVR in patients with HCV genotype 3 and cirrhosis. [Gastroenterology 2018;155:1120-1127.e4]
Nonetheless, taking into account the heterogeneity of HCV, the inclusion of patients from only five Asian countries may have limited the generalization of the findings to other populations, they said.