Meeting News Coverage

ASTRAL-4: Sovaldi/velpatasvir shows high SVR for decompensated cirrhosis

A fixed-dose combination of Sovaldi and velpatasvir with or without ribavirin yielded sustained virologic response rates greater than 80% in patients with hepatitis C virus infection and decompensated cirrhosis.

“There have been few treatment options available for treating hepatitis C infection in patients with existing cirrhosis and liver failure,” Michael Curry, MD, director of hepatology and medical director of liver transplantation at Beth Israel Deaconess Medical Center and associate professor of medicine at Harvard Medical School, said in a press release. “Our study found that early improvements in liver function were seen in a substantial portion of the study participants, as indicated by improvement in the Childs Pugh score, which assesses severity of liver cirrhosis, and the MELD score, which is used to determine patient priority for liver transplantation.”

In this phase 3 clinical trial known as ASTRAL-4, Curry and colleagues randomly assigned 267 patients with decompensated cirrhosis, according to HCV genotype, either Sovaldi (sofosbuvir, Gilead Sciences) and velpatasvir (GS-5816, Gilead Sciences; n = 90) once daily for 12 weeks, sofosbuvir and velpatasvir plus ribavirin for 12 weeks (n = 87) or sofosbuvir plus velpatasvir for 24 weeks (n = 90). Of these patients, 78% had HCV genotype 1, 4% had genotype 2, 15% had genotype 3, 3% had genotype 4, less than 1% had genotype 6 and no patients had genotype 5.

Michael Curry, MD

Michael Curry

Patients who received sofosbuvir and velpatasvir for 12 weeks yielded an SVR of 83% (95% CI, 74%-90%) across all genotypes; patients who received sofosbuvir and velpatasvir plus ribavirin for 12 weeks yielded an SVR of 94% (95% CI, 87%-98%); and patients who received sofosbuvir and velpatasvir for 24 weeks yielded an SVR of 86% (95% CI, 77%-92%).

“Our trial showed that using a daily combination of the antiviral medications sofosbuvir and velpatasvir, with or without the addition of ribavirin for 12 weeks or 24 weeks, successfully treated hepatitis C in 83% to 94% of patients,” Curry said.

All three SVR rates were superior to the “assumed spontaneous rate of HCV clearance” at 12 weeks after therapy (P < .001), according to the research. In a post-hoc analysis, no significant differences in SVR rates among the three cohorts were observed.

Among all the patients, 22 experienced virologic failure; 11 who received sofosbuvir and velpatasvir for 12 weeks; three who received sofosbuvir and velpatasvir plus ribavirin for 12 weeks; and eight who received sofosbuvir and velpatasvir for 24 weeks.

Serious adverse events were observed in all three study groups: 19% of patients who received sofosbuvir and velpatasvir for 12 weeks, 16% who received sofosbuvir and velpatasvir plus ribavirin for 12 weeks and 18% who received sofosbuvir and velpatasvir for 24 weeks.

The most common adverse events were fatigue (29%), nausea (23%) and headache (22%) in all three patient groups. However, anemia was only common among patients receiving ribavirin (31%).

“The number of patients with liver failure due to hepatitis C is expected to substantially increase over the next 10 years,” Curry said. “These new findings indicate that patients with more advanced liver disease can still benefit from treatment of hepatitis C — and that elimination of this infection is associated with early improvement in liver function.”

Though recently published, this study was also chosen as a Late Breaker highlight at The Liver Meeting 2015.

Disclosures: The study was funded by Gilead Sciences. Please see the study for a full list of all authors’ relevant financial disclosures.

A fixed-dose combination of Sovaldi and velpatasvir with or without ribavirin yielded sustained virologic response rates greater than 80% in patients with hepatitis C virus infection and decompensated cirrhosis.

“There have been few treatment options available for treating hepatitis C infection in patients with existing cirrhosis and liver failure,” Michael Curry, MD, director of hepatology and medical director of liver transplantation at Beth Israel Deaconess Medical Center and associate professor of medicine at Harvard Medical School, said in a press release. “Our study found that early improvements in liver function were seen in a substantial portion of the study participants, as indicated by improvement in the Childs Pugh score, which assesses severity of liver cirrhosis, and the MELD score, which is used to determine patient priority for liver transplantation.”

In this phase 3 clinical trial known as ASTRAL-4, Curry and colleagues randomly assigned 267 patients with decompensated cirrhosis, according to HCV genotype, either Sovaldi (sofosbuvir, Gilead Sciences) and velpatasvir (GS-5816, Gilead Sciences; n = 90) once daily for 12 weeks, sofosbuvir and velpatasvir plus ribavirin for 12 weeks (n = 87) or sofosbuvir plus velpatasvir for 24 weeks (n = 90). Of these patients, 78% had HCV genotype 1, 4% had genotype 2, 15% had genotype 3, 3% had genotype 4, less than 1% had genotype 6 and no patients had genotype 5.

Michael Curry, MD

Michael Curry

Patients who received sofosbuvir and velpatasvir for 12 weeks yielded an SVR of 83% (95% CI, 74%-90%) across all genotypes; patients who received sofosbuvir and velpatasvir plus ribavirin for 12 weeks yielded an SVR of 94% (95% CI, 87%-98%); and patients who received sofosbuvir and velpatasvir for 24 weeks yielded an SVR of 86% (95% CI, 77%-92%).

“Our trial showed that using a daily combination of the antiviral medications sofosbuvir and velpatasvir, with or without the addition of ribavirin for 12 weeks or 24 weeks, successfully treated hepatitis C in 83% to 94% of patients,” Curry said.

All three SVR rates were superior to the “assumed spontaneous rate of HCV clearance” at 12 weeks after therapy (P < .001), according to the research. In a post-hoc analysis, no significant differences in SVR rates among the three cohorts were observed.

Among all the patients, 22 experienced virologic failure; 11 who received sofosbuvir and velpatasvir for 12 weeks; three who received sofosbuvir and velpatasvir plus ribavirin for 12 weeks; and eight who received sofosbuvir and velpatasvir for 24 weeks.

Serious adverse events were observed in all three study groups: 19% of patients who received sofosbuvir and velpatasvir for 12 weeks, 16% who received sofosbuvir and velpatasvir plus ribavirin for 12 weeks and 18% who received sofosbuvir and velpatasvir for 24 weeks.

The most common adverse events were fatigue (29%), nausea (23%) and headache (22%) in all three patient groups. However, anemia was only common among patients receiving ribavirin (31%).

“The number of patients with liver failure due to hepatitis C is expected to substantially increase over the next 10 years,” Curry said. “These new findings indicate that patients with more advanced liver disease can still benefit from treatment of hepatitis C — and that elimination of this infection is associated with early improvement in liver function.”

Though recently published, this study was also chosen as a Late Breaker highlight at The Liver Meeting 2015.

Disclosures: The study was funded by Gilead Sciences. Please see the study for a full list of all authors’ relevant financial disclosures.