In the Journals

Combination sofosbuvir, ravidasvir effective in HCV genotype 4

For patients with hepatitis C genotype 4, treatment with ravidasvir and sofosbuvir, with or without ribavirin, was safe and effective regardless of cirrhosis or previous interferon-based treatment experience.

“[Ravidasvir (RDV)] is a pan-genotypic anti-HCV NS5A inhibitor with a favorable pharmacokinetic profile, rapid plasma concentrations, and high [24-hour] trough concentrations, allowing for continuous HCV inhibitory drug concentrations with once daily oral dosing,” Gamal Esmat, MD, from Cairo University, Egypt, and colleagues wrote. “RDV achieves steady-state with the first dose, and from day 2 onward, peak and trough levels remain constant without evidence for either subsequent drug accumulation or drug induced clearance.”

The study comprised 298 adult patients with HCV genotype 4 and no coinfection with hepatitis B, HIV or mixed genotypes. One group of patients (n = 149) were treatment naive, 59 of whom had cirrhosis. A second group (n = 149) had unsuccessfully undergone treatment with interferon-based therapy previously, 70 of whom had cirrhosis.

During the study, seven patients were lost to follow-up due to withdrawn consent, a serious adverse event unrelated to treatment, or death unrelated to treatment.

At the end of 24 weeks, 282 patients achieved sustained virologic response (94.6%; 95% CI, 91.5-96.7). Two patients did not return for their 12 week SVR assessment, but met SVR at 24 weeks; including these two patients increased the SVR rate to 95.3% (95% CI, 92.3-97.2).

The researchers observed no virologic failures in patients without cirrhosis. Seven patients with cirrhosis experienced virologic relapse, three of whom were treatment-experienced. The SVR rate, however, was similar between all treatment-naive and treatment-experienced patients.

While cirrhosis did decrease response in certain patients, the addition of ribavirin did not affect therapy outcome.

Throughout both groups, 69% of patients reported adverse events. Most adverse events were mild or moderate and the most common included headache, fatigue, abdominal pain and pruritus. The researchers judged that approximately half of the reported adverse events were unlikely related to therapy.

Eleven severe adverse events occurred in 11 different patients, two of which led to study discontinuation. The two severe adverse events that led to discontinuation included a case of hearing impairment and a transient episode of symptomatic bradycardia.

“While there are several very effective treatments for HCV [genotype 4], the combination of [sofosbuvir (SOF) and RDV] has the potential to be a very cheap option both in Egypt (with the availability of generic SOF, and with RDV developed by a local company that is promising a very cheap local market price) and to all low and middle income countries (LMICs) through its development with Drugs for Neglected Diseases Initiative, who are also promising to make medications for HCV affordable to all LMICs (including this combination if ongoing trials in other genotypes also prove effective),” the researchers concluded. – by Talitha Bennett

Disclosure: Esmat reports he received financial support from AbbVie, Gilead, GlaxoSmithKline, Janssen, Merck Sharp & Dohme, Pharco and Roche. Please see the full study for the other authors’ relevant financial disclosures.

For patients with hepatitis C genotype 4, treatment with ravidasvir and sofosbuvir, with or without ribavirin, was safe and effective regardless of cirrhosis or previous interferon-based treatment experience.

“[Ravidasvir (RDV)] is a pan-genotypic anti-HCV NS5A inhibitor with a favorable pharmacokinetic profile, rapid plasma concentrations, and high [24-hour] trough concentrations, allowing for continuous HCV inhibitory drug concentrations with once daily oral dosing,” Gamal Esmat, MD, from Cairo University, Egypt, and colleagues wrote. “RDV achieves steady-state with the first dose, and from day 2 onward, peak and trough levels remain constant without evidence for either subsequent drug accumulation or drug induced clearance.”

The study comprised 298 adult patients with HCV genotype 4 and no coinfection with hepatitis B, HIV or mixed genotypes. One group of patients (n = 149) were treatment naive, 59 of whom had cirrhosis. A second group (n = 149) had unsuccessfully undergone treatment with interferon-based therapy previously, 70 of whom had cirrhosis.

During the study, seven patients were lost to follow-up due to withdrawn consent, a serious adverse event unrelated to treatment, or death unrelated to treatment.

At the end of 24 weeks, 282 patients achieved sustained virologic response (94.6%; 95% CI, 91.5-96.7). Two patients did not return for their 12 week SVR assessment, but met SVR at 24 weeks; including these two patients increased the SVR rate to 95.3% (95% CI, 92.3-97.2).

The researchers observed no virologic failures in patients without cirrhosis. Seven patients with cirrhosis experienced virologic relapse, three of whom were treatment-experienced. The SVR rate, however, was similar between all treatment-naive and treatment-experienced patients.

While cirrhosis did decrease response in certain patients, the addition of ribavirin did not affect therapy outcome.

Throughout both groups, 69% of patients reported adverse events. Most adverse events were mild or moderate and the most common included headache, fatigue, abdominal pain and pruritus. The researchers judged that approximately half of the reported adverse events were unlikely related to therapy.

Eleven severe adverse events occurred in 11 different patients, two of which led to study discontinuation. The two severe adverse events that led to discontinuation included a case of hearing impairment and a transient episode of symptomatic bradycardia.

“While there are several very effective treatments for HCV [genotype 4], the combination of [sofosbuvir (SOF) and RDV] has the potential to be a very cheap option both in Egypt (with the availability of generic SOF, and with RDV developed by a local company that is promising a very cheap local market price) and to all low and middle income countries (LMICs) through its development with Drugs for Neglected Diseases Initiative, who are also promising to make medications for HCV affordable to all LMICs (including this combination if ongoing trials in other genotypes also prove effective),” the researchers concluded. – by Talitha Bennett

Disclosure: Esmat reports he received financial support from AbbVie, Gilead, GlaxoSmithKline, Janssen, Merck Sharp & Dohme, Pharco and Roche. Please see the full study for the other authors’ relevant financial disclosures.