More affordable direct-acting antiviral treatments are needed to treat hepatitis c virus (HCV) infections in low and middle-income countries. One potential answer is the combination of ravidasvir, a pangenotypic non-structural protein 5A (NS5A) inhibitor, and sofosbuvir, which has shown efficacy and safety for patients with chronic HCV genotype 4 infections.
A team, led by Isabelle Andrieux-Meyer, MD, assessed the efficacy and safety of ravidasvir plus sofosbuvir in a diverse population of adults with chronic HCV infections.
In the two-stage, open-label, phase 2/3 single-arm STORM-C-1 trial, the researchers examined HCV patients in 6 public academic and non-academic centers in Malaysia and 4 public academic and non-academic centers in Thailand.
Eligible patients included HCV with compensated cirrhosis (Metavir F4 and Child-Turcotte-Pugh class A) or without cirrhosis (Metavir F0–3) aged 18–69 years were eligible to participate, regardless of HCV genotype, HIV infection status, previous interferon-based HCV treatment, or source of HCV infection.
Differences in Genotypes
Of the 301 patients enrolled in stage 1 of the study, 98 (33%) patients had genotype 1a infection, 27 (9%) had genotype 1b infection, two (1%) had genotype 2 infection, 158 (52%) had genotype 3 infection, and 16 (5%) had genotype 6 infection.
In addition, 81 (27%) patients had compensated cirrhosis, 90 (30%) had HIV co-infection, and 99 (33%) had received previous interferon-based treatment.
The treatment included once daily ravidasvir (200 mg) and sofosbuvir (400 mg) for 12 weeks without cirrhosis and for 24 weeks for patients with cirrhosis.
The investigators sought primary endpoints of sustained virological response at 12 weeks following treatment (SVR12), defined as HCV RNA 12 IU/mL in Thailand and HCV RNA <15 IU/mL in Malaysia at 12 weeks after the end of treatment.
There were some common treatment-emergent adverse events found in the study, including pyrexia (n = 35; 12%), cough (n = 26; 9%), upper respiratory tract infection (n = 23; 8%), and headache (n = 20; 7%).
However, there were no deaths or treatment discontinuations caused by serious adverse events in the study and of the 300 patients included in the final analysis, 291 (97%; 95% CI, 94-99) achieved SVR12.
SVR12 was also reported in 78 (96%) patients with cirrhosis and 153 (97%) patients with genotype 3 infection, including 51 (96%) patients with cirrhosis.
Finally, there was no difference in SVR12 rates by HIV co-infection or previous interferon treatment.
“In this first stage, ravidasvir plus sofosbuvir was effective and well tolerated in this diverse adult population of patients with chronic HCV infection,” the authors wrote. “Ravidasvir plus sofosbuvir has the potential to provide an additional affordable, simple, and efficacious public health tool for large-scale implementation to eliminate HCV as a cause of morbidity and mortality.”
The study, “Efficacy and safety of ravidasvir plus sofosbuvir in patients with chronic hepatitis C infection without cirrhosis or with compensated cirrhosis (STORM-C-1): interim analysis of a two-stage, open-label, multicenter, single arm, phase 2/3 trial,” was published online in The Lancet Gastroenterology & Hepatology.