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Patients with chronic hepatitis C who develop cirrhosis with severe portal hypertension are at greater risk of progressing to liver decompensation within the first 5 years of treatment, even if they show a sustained virologic response to therapy, a cohort study has found.

The study of 100 patients with hepatitis C and compensated cirrhosis showed that the probability of developing a first episode of liver decompensation at 1, 5, and 7 years was 4%, 25%, and 28%, respectively, among patients with an hepatic venous pressure gradient (HVPG) value of 10 mm Hg or above, compared with 0, 0, and 16% in patients without cirrhosis with severe portal hypertension (CSPH).

Courtesy NIH

Nearly three-quarters of the patients in the study had CSPH at baseline and 35% achieved a sustained virologic response, while 19% developed liver decompensation, according to Dr. Sabela Lens of the Institut d’Investigacions Biomèdiques August-Pi-Sunyer, Barcelona, and coauthors.

“Although viral clearance was associated with a significant reduction in HVPG, this effect, at least 24 weeks after the end of treatment, was mild and only one-third of patients with a high-risk baseline situation with CSPH shifted to a condition of low risk for developing liver decompensation,” they wrote (Clin Gastro Hepatol. 2015. doi: 10.1016/j.cgh.2015.04.013).

“The results of our study show that baseline HVPG value before antiviral treatment is a strong predictor of liver decompensation on follow-up evaluation,” Dr. Lens and associates noted.

The study was funded by the Instituto de Salud Carlos III, and one author was funded by an unrestricted grant from Roche. There were no other conflicts of interest declared.

Patients with chronic hepatitis C who develop cirrhosis with severe portal hypertension are at greater risk of progressing to liver decompensation within the first 5 years of treatment, even if they show a sustained virologic response to therapy, a cohort study has found.

The study of 100 patients with hepatitis C and compensated cirrhosis showed that the probability of developing a first episode of liver decompensation at 1, 5, and 7 years was 4%, 25%, and 28%, respectively, among patients with an hepatic venous pressure gradient (HVPG) value of 10 mm Hg or above, compared with 0, 0, and 16% in patients without cirrhosis with severe portal hypertension (CSPH).

Courtesy NIH

Nearly three-quarters of the patients in the study had CSPH at baseline and 35% achieved a sustained virologic response, while 19% developed liver decompensation, according to Dr. Sabela Lens of the Institut d’Investigacions Biomèdiques August-Pi-Sunyer, Barcelona, and coauthors.

“Although viral clearance was associated with a significant reduction in HVPG, this effect, at least 24 weeks after the end of treatment, was mild and only one-third of patients with a high-risk baseline situation with CSPH shifted to a condition of low risk for developing liver decompensation,” they wrote (Clin Gastro Hepatol. 2015. doi: 10.1016/j.cgh.2015.04.013).

“The results of our study show that baseline HVPG value before antiviral treatment is a strong predictor of liver decompensation on follow-up evaluation,” Dr. Lens and associates noted.

The study was funded by the Instituto de Salud Carlos III, and one author was funded by an unrestricted grant from Roche. There were no other conflicts of interest declared.

Patients with chronic hepatitis C who develop cirrhosis with severe portal hypertension are at greater risk of progressing to liver decompensation within the first 5 years of treatment, even if they show a sustained virologic response to therapy, a cohort study has found.

The study of 100 patients with hepatitis C and compensated cirrhosis showed that the probability of developing a first episode of liver decompensation at 1, 5, and 7 years was 4%, 25%, and 28%, respectively, among patients with an hepatic venous pressure gradient (HVPG) value of 10 mm Hg or above, compared with 0, 0, and 16% in patients without cirrhosis with severe portal hypertension (CSPH).

Courtesy NIH

Nearly three-quarters of the patients in the study had CSPH at baseline and 35% achieved a sustained virologic response, while 19% developed liver decompensation, according to Dr. Sabela Lens of the Institut d’Investigacions Biomèdiques August-Pi-Sunyer, Barcelona, and coauthors.

“Although viral clearance was associated with a significant reduction in HVPG, this effect, at least 24 weeks after the end of treatment, was mild and only one-third of patients with a high-risk baseline situation with CSPH shifted to a condition of low risk for developing liver decompensation,” they wrote (Clin Gastro Hepatol. 2015. doi: 10.1016/j.cgh.2015.04.013).

“The results of our study show that baseline HVPG value before antiviral treatment is a strong predictor of liver decompensation on follow-up evaluation,” Dr. Lens and associates noted.

The study was funded by the Instituto de Salud Carlos III, and one author was funded by an unrestricted grant from Roche. There were no other conflicts of interest declared.

Combination treatment with ledipasvir, sofosbuvir, and ribavirin for chronic hepatitis C virus infection led to sustained viral response (SVR) rates of 86%-89% among nontransplanted patients and 60%-100% among transplant recipients, according to a study published in the September issue of Gastroenterology.

“Rates of SVR were over 85% in every group of patients with Child-Pugh class [CPC] B decompensated cirrhosis – in those who had and had not undergone liver transplantation, as well as those who were receiving 12 and 24 weeks of treatment,” said Dr. Michael Charlton of Intermountain Medical Center in Salt Lake City, and his associates. “Similar response rates were observed in Child-Pugh class C patients who had not undergone liver transplantation. Rates of response were numerically lower in liver transplant recipients with Child-Pugh class C disease, but the small sample size ... makes this a preliminary observation.”

Patients with chronic HCV infection and advanced liver disease have a poor prognosis because of their risk of liver failure and hepatocellular carcinoma and because they have very limited treatment options. Chances of reinfection are 100% if patients have detectable virus at transplantation, and reinfection increases rates of subsequent graft loss, morbidity, and mortality, the investigators noted.

To assess the recently approved sofosbuvir-ledipasvir regimen, they conducted an open-label, phase II trial (SOLAR-1) of the combination plus ribavirin in 337 HCV-infected patients with advanced liver disease, including transplant recipients. Nearly all (99%) of the patients had HCV genotype 1 infection, while 1% had genotype 4 infection. The investigators randomized patients to receive 90 mg ledipasvir and 400 mg sofosbuvir in a fixed-dose daily regimen for either 12 or 24 weeks in combination with ribavirin, which was dosed based on body weight, tolerance of side effects, and extent of liver disease. Patients with CPC C cirrhosis received lower doses of ribavirin because of increased risk of hemotoxicity (Gastroenterology 2015 May 15. doi:10.1053/j.gastro.2015.05.010).

Nontransplanted patients who had decompensated cirrhosis achieved SVR12 or SVR24 rates of 86%-89%, even if they had CPC C decompensated disease, the researchers reported. “Our results also demonstrate that SVR12 in patients with decompensated cirrhosis is associated with early improvements in CPC and MELD [Model for End-Stage Liver Disease] scores, suggesting that eradication of the virus can rapidly improve hepatic function by attenuating the injury and inflammation due to HCV replication,” they said. Patients with CPC B disease also had significant improvements in albumin and bilirubin levels after 4 weeks of treatment.

Among transplant recipients who were noncirrhotic or were in compensated cirrhosis, SVR rates ranged from 96% to 98%, regardless of treatment duration or presence of cirrhosis, Dr. Charlton and associates reported. Among transplant recipients with decompensated cirrhosis, SVR rates were 86%-88% for the subgroup with CPC B disease, but were 60% for CPC C patients who were treated for 12 weeks, and were 75% for CPC C patients who were treated for 24 weeks. In contrast, all six patients with fibrosing cholestatic hepatitis achieved SVR and also experienced large drops in total bilirubin levels within 2-4 weeks of starting treatment, the researchers said. Finally, among the seven patients who underwent liver transplantation either during treatment or before posttreatment week 12, six achieved virologic response after surgery, and one died of multiorgan failure and septic shock 1 day after testing negative for HCV RNA.

In all, 13 patients (4%) discontinued treatment because of adverse events, primarily liver decompensation, the researchers reported. Adverse events that led more than one patient to stop treatment included sepsis, renal failure, dyspnea, and gastrointestinal hemorrhage. Patients were more likely to stop taking ribavirin if they were treated for 24 weeks or had worsening disease. Ten patients died on study, but none of the deaths were thought to be related to treatment, the researchers wrote.

Dr. Charlton disclosed ties with Gilead Sciences, maker of sofosbuvir and ledipasvir. Gilead funded the study. Four coauthors reported having no conflicts; the other 25 investigators reported employment or other financial ties with numerous pharmaceutical companies.

Combination treatment with ledipasvir, sofosbuvir, and ribavirin for chronic hepatitis C virus infection led to sustained viral response (SVR) rates of 86%-89% among nontransplanted patients and 60%-100% among transplant recipients, according to a study published in the September issue of Gastroenterology.

“Rates of SVR were over 85% in every group of patients with Child-Pugh class [CPC] B decompensated cirrhosis – in those who had and had not undergone liver transplantation, as well as those who were receiving 12 and 24 weeks of treatment,” said Dr. Michael Charlton of Intermountain Medical Center in Salt Lake City, and his associates. “Similar response rates were observed in Child-Pugh class C patients who had not undergone liver transplantation. Rates of response were numerically lower in liver transplant recipients with Child-Pugh class C disease, but the small sample size ... makes this a preliminary observation.”

Patients with chronic HCV infection and advanced liver disease have a poor prognosis because of their risk of liver failure and hepatocellular carcinoma and because they have very limited treatment options. Chances of reinfection are 100% if patients have detectable virus at transplantation, and reinfection increases rates of subsequent graft loss, morbidity, and mortality, the investigators noted.

To assess the recently approved sofosbuvir-ledipasvir regimen, they conducted an open-label, phase II trial (SOLAR-1) of the combination plus ribavirin in 337 HCV-infected patients with advanced liver disease, including transplant recipients. Nearly all (99%) of the patients had HCV genotype 1 infection, while 1% had genotype 4 infection. The investigators randomized patients to receive 90 mg ledipasvir and 400 mg sofosbuvir in a fixed-dose daily regimen for either 12 or 24 weeks in combination with ribavirin, which was dosed based on body weight, tolerance of side effects, and extent of liver disease. Patients with CPC C cirrhosis received lower doses of ribavirin because of increased risk of hemotoxicity (Gastroenterology 2015 May 15. doi:10.1053/j.gastro.2015.05.010).

Nontransplanted patients who had decompensated cirrhosis achieved SVR12 or SVR24 rates of 86%-89%, even if they had CPC C decompensated disease, the researchers reported. “Our results also demonstrate that SVR12 in patients with decompensated cirrhosis is associated with early improvements in CPC and MELD [Model for End-Stage Liver Disease] scores, suggesting that eradication of the virus can rapidly improve hepatic function by attenuating the injury and inflammation due to HCV replication,” they said. Patients with CPC B disease also had significant improvements in albumin and bilirubin levels after 4 weeks of treatment.

Among transplant recipients who were noncirrhotic or were in compensated cirrhosis, SVR rates ranged from 96% to 98%, regardless of treatment duration or presence of cirrhosis, Dr. Charlton and associates reported. Among transplant recipients with decompensated cirrhosis, SVR rates were 86%-88% for the subgroup with CPC B disease, but were 60% for CPC C patients who were treated for 12 weeks, and were 75% for CPC C patients who were treated for 24 weeks. In contrast, all six patients with fibrosing cholestatic hepatitis achieved SVR and also experienced large drops in total bilirubin levels within 2-4 weeks of starting treatment, the researchers said. Finally, among the seven patients who underwent liver transplantation either during treatment or before posttreatment week 12, six achieved virologic response after surgery, and one died of multiorgan failure and septic shock 1 day after testing negative for HCV RNA.

In all, 13 patients (4%) discontinued treatment because of adverse events, primarily liver decompensation, the researchers reported. Adverse events that led more than one patient to stop treatment included sepsis, renal failure, dyspnea, and gastrointestinal hemorrhage. Patients were more likely to stop taking ribavirin if they were treated for 24 weeks or had worsening disease. Ten patients died on study, but none of the deaths were thought to be related to treatment, the researchers wrote.

Dr. Charlton disclosed ties with Gilead Sciences, maker of sofosbuvir and ledipasvir. Gilead funded the study. Four coauthors reported having no conflicts; the other 25 investigators reported employment or other financial ties with numerous pharmaceutical companies.

Combination treatment with ledipasvir, sofosbuvir, and ribavirin for chronic hepatitis C virus infection led to sustained viral response (SVR) rates of 86%-89% among nontransplanted patients and 60%-100% among transplant recipients, according to a study published in the September issue of Gastroenterology.

“Rates of SVR were over 85% in every group of patients with Child-Pugh class [CPC] B decompensated cirrhosis – in those who had and had not undergone liver transplantation, as well as those who were receiving 12 and 24 weeks of treatment,” said Dr. Michael Charlton of Intermountain Medical Center in Salt Lake City, and his associates. “Similar response rates were observed in Child-Pugh class C patients who had not undergone liver transplantation. Rates of response were numerically lower in liver transplant recipients with Child-Pugh class C disease, but the small sample size ... makes this a preliminary observation.”

Patients with chronic HCV infection and advanced liver disease have a poor prognosis because of their risk of liver failure and hepatocellular carcinoma and because they have very limited treatment options. Chances of reinfection are 100% if patients have detectable virus at transplantation, and reinfection increases rates of subsequent graft loss, morbidity, and mortality, the investigators noted.

To assess the recently approved sofosbuvir-ledipasvir regimen, they conducted an open-label, phase II trial (SOLAR-1) of the combination plus ribavirin in 337 HCV-infected patients with advanced liver disease, including transplant recipients. Nearly all (99%) of the patients had HCV genotype 1 infection, while 1% had genotype 4 infection. The investigators randomized patients to receive 90 mg ledipasvir and 400 mg sofosbuvir in a fixed-dose daily regimen for either 12 or 24 weeks in combination with ribavirin, which was dosed based on body weight, tolerance of side effects, and extent of liver disease. Patients with CPC C cirrhosis received lower doses of ribavirin because of increased risk of hemotoxicity (Gastroenterology 2015 May 15. doi:10.1053/j.gastro.2015.05.010).

Nontransplanted patients who had decompensated cirrhosis achieved SVR12 or SVR24 rates of 86%-89%, even if they had CPC C decompensated disease, the researchers reported. “Our results also demonstrate that SVR12 in patients with decompensated cirrhosis is associated with early improvements in CPC and MELD [Model for End-Stage Liver Disease] scores, suggesting that eradication of the virus can rapidly improve hepatic function by attenuating the injury and inflammation due to HCV replication,” they said. Patients with CPC B disease also had significant improvements in albumin and bilirubin levels after 4 weeks of treatment.

Among transplant recipients who were noncirrhotic or were in compensated cirrhosis, SVR rates ranged from 96% to 98%, regardless of treatment duration or presence of cirrhosis, Dr. Charlton and associates reported. Among transplant recipients with decompensated cirrhosis, SVR rates were 86%-88% for the subgroup with CPC B disease, but were 60% for CPC C patients who were treated for 12 weeks, and were 75% for CPC C patients who were treated for 24 weeks. In contrast, all six patients with fibrosing cholestatic hepatitis achieved SVR and also experienced large drops in total bilirubin levels within 2-4 weeks of starting treatment, the researchers said. Finally, among the seven patients who underwent liver transplantation either during treatment or before posttreatment week 12, six achieved virologic response after surgery, and one died of multiorgan failure and septic shock 1 day after testing negative for HCV RNA.

In all, 13 patients (4%) discontinued treatment because of adverse events, primarily liver decompensation, the researchers reported. Adverse events that led more than one patient to stop treatment included sepsis, renal failure, dyspnea, and gastrointestinal hemorrhage. Patients were more likely to stop taking ribavirin if they were treated for 24 weeks or had worsening disease. Ten patients died on study, but none of the deaths were thought to be related to treatment, the researchers wrote.

Dr. Charlton disclosed ties with Gilead Sciences, maker of sofosbuvir and ledipasvir. Gilead funded the study. Four coauthors reported having no conflicts; the other 25 investigators reported employment or other financial ties with numerous pharmaceutical companies.

More than 28% of patients with chronic hepatitis C (CHC) virus infection met at least one criterion for cirrhosis, while only 7% had biopsy confirmation of the condition, investigators reported in the August issue of the American Journal of Gastroenterology.

Furthermore, only half of the patients with a positive biopsy had been given an associated ICD-9-CM code, said Dr. Stuart Gordon at Henry Ford Health System in Detroit and his associates. Cirrhosis in CHC therefore might often go unreported, leading to “overly conservative” estimates of its prevalence, associated health care costs, and the cost-effectiveness of the newer HCV treatments, they said.

©Sebastian Kaulitzki/thinkstockphotos.com

The researchers analyzed data for 9,783 patients with CHC from the Chronic Hepatitis Cohort Study who were treated between 2006 and 2010. They compared the prevalence of biopsy-confirmed cirrhosis (Metavir stage 4 or pathologist’s report) with the proportion of patients who met at least one of four criteria: positive biopsy; Fibrosis-4 score of at least 5.88, or the presence of a diagnosis or procedural code for cirrhosis or hepatic decompensation. Patients averaged 55 years of age, and most were white males with health insurance, the researchers said (Am. J. Gastroenterol. 2015;110:1169-77).

In all, 28.5% of CHC patients met at least one of the four criteria, including 22% who met the Fibrosis-4 threshold, 6.8% who were biopsy positive, and 5.7% and 4.9% who had a diagnostic or procedural code for cirrhosis or hepatic decompensation, respectively, said the investigators. Patients had significantly greater odds of cirrhosis (P less than .05) if they were older, male, Asian, Hispanic, had genotype 3 HCV infection, HIV coinfection, or a history of antiviral treatment, alcohol abuse, or diabetes, they added. “Our findings are the first in the United States to attempt an accurate estimate of the prevalence of cirrhosis in the CHC patient population at large,” the researchers concluded. “Use of additional parameters suggests a fourfold higher prevalence of cirrhosis than is revealed by biopsy alone. These findings suggest that cirrhosis in CHC patients may be significantly underdocumented and underdiagnosed.”

The CDC Foundation funds the Chronic Hepatitis Cohort Study. Dr. Gordon reported financial relationships with numerous makers of anti-HCV therapies. The other investigators reported having no conflicts of interest.

ginews@gastro.org

More than 28% of patients with chronic hepatitis C (CHC) virus infection met at least one criterion for cirrhosis, while only 7% had biopsy confirmation of the condition, investigators reported in the August issue of the American Journal of Gastroenterology.

Furthermore, only half of the patients with a positive biopsy had been given an associated ICD-9-CM code, said Dr. Stuart Gordon at Henry Ford Health System in Detroit and his associates. Cirrhosis in CHC therefore might often go unreported, leading to “overly conservative” estimates of its prevalence, associated health care costs, and the cost-effectiveness of the newer HCV treatments, they said.

©Sebastian Kaulitzki/thinkstockphotos.com

The researchers analyzed data for 9,783 patients with CHC from the Chronic Hepatitis Cohort Study who were treated between 2006 and 2010. They compared the prevalence of biopsy-confirmed cirrhosis (Metavir stage 4 or pathologist’s report) with the proportion of patients who met at least one of four criteria: positive biopsy; Fibrosis-4 score of at least 5.88, or the presence of a diagnosis or procedural code for cirrhosis or hepatic decompensation. Patients averaged 55 years of age, and most were white males with health insurance, the researchers said (Am. J. Gastroenterol. 2015;110:1169-77).

In all, 28.5% of CHC patients met at least one of the four criteria, including 22% who met the Fibrosis-4 threshold, 6.8% who were biopsy positive, and 5.7% and 4.9% who had a diagnostic or procedural code for cirrhosis or hepatic decompensation, respectively, said the investigators. Patients had significantly greater odds of cirrhosis (P less than .05) if they were older, male, Asian, Hispanic, had genotype 3 HCV infection, HIV coinfection, or a history of antiviral treatment, alcohol abuse, or diabetes, they added. “Our findings are the first in the United States to attempt an accurate estimate of the prevalence of cirrhosis in the CHC patient population at large,” the researchers concluded. “Use of additional parameters suggests a fourfold higher prevalence of cirrhosis than is revealed by biopsy alone. These findings suggest that cirrhosis in CHC patients may be significantly underdocumented and underdiagnosed.”

The CDC Foundation funds the Chronic Hepatitis Cohort Study. Dr. Gordon reported financial relationships with numerous makers of anti-HCV therapies. The other investigators reported having no conflicts of interest.

ginews@gastro.org

More than 28% of patients with chronic hepatitis C (CHC) virus infection met at least one criterion for cirrhosis, while only 7% had biopsy confirmation of the condition, investigators reported in the August issue of the American Journal of Gastroenterology.

Furthermore, only half of the patients with a positive biopsy had been given an associated ICD-9-CM code, said Dr. Stuart Gordon at Henry Ford Health System in Detroit and his associates. Cirrhosis in CHC therefore might often go unreported, leading to “overly conservative” estimates of its prevalence, associated health care costs, and the cost-effectiveness of the newer HCV treatments, they said.

©Sebastian Kaulitzki/thinkstockphotos.com

The researchers analyzed data for 9,783 patients with CHC from the Chronic Hepatitis Cohort Study who were treated between 2006 and 2010. They compared the prevalence of biopsy-confirmed cirrhosis (Metavir stage 4 or pathologist’s report) with the proportion of patients who met at least one of four criteria: positive biopsy; Fibrosis-4 score of at least 5.88, or the presence of a diagnosis or procedural code for cirrhosis or hepatic decompensation. Patients averaged 55 years of age, and most were white males with health insurance, the researchers said (Am. J. Gastroenterol. 2015;110:1169-77).

In all, 28.5% of CHC patients met at least one of the four criteria, including 22% who met the Fibrosis-4 threshold, 6.8% who were biopsy positive, and 5.7% and 4.9% who had a diagnostic or procedural code for cirrhosis or hepatic decompensation, respectively, said the investigators. Patients had significantly greater odds of cirrhosis (P less than .05) if they were older, male, Asian, Hispanic, had genotype 3 HCV infection, HIV coinfection, or a history of antiviral treatment, alcohol abuse, or diabetes, they added. “Our findings are the first in the United States to attempt an accurate estimate of the prevalence of cirrhosis in the CHC patient population at large,” the researchers concluded. “Use of additional parameters suggests a fourfold higher prevalence of cirrhosis than is revealed by biopsy alone. These findings suggest that cirrhosis in CHC patients may be significantly underdocumented and underdiagnosed.”

The CDC Foundation funds the Chronic Hepatitis Cohort Study. Dr. Gordon reported financial relationships with numerous makers of anti-HCV therapies. The other investigators reported having no conflicts of interest.

ginews@gastro.org

The U.S. Food and Drug Administration has approved Daklinza (daclatasvir), a hepatitis C virus (HCV) drug that, when used in combination with sofosbuvir, does not require coadministration of interferon or ribavirin for the treatment of HCV genotype 3 infections, the agency announced in a statement on July 24, 2015.

In a clinical trial, 152 treatment-naive and treatment-experienced participants with chronic HCV genotype 3 infection received Daklinza 60 mg plus sofosbuvir 400 mg once daily for 12 weeks, and were monitored for 24 weeks post treatment; 98% of the treatment-naive participants with no cirrhosis of the liver (and 58% of the treatment-naive participants with cirrhosis) achieved a sustained virologic response. Among the participants who were treatment experienced, 92% with no cirrhosis of the liver and 69% with cirrhosis achieved sustained virologic response.

“Today’s approval provides a new option for patients with genotype 3 HCV, including those patients who cannot tolerate ribavirin,” said Dr. Edward Cox, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, in a statement.

The most common side effects of Daklinza with sofosbuvir were fatigue and headache.

According to the Centers for Disease Control and Prevention, approximately 2.7 million Americans are infected with HCV of which approximately 10 percent are genotype 3.

Daklinza is marketed by Bristol-Myers Squibb, based in Princeton, N.J.

Read the full FDA statement at: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm455888.htm.

The U.S. Food and Drug Administration has approved Daklinza (daclatasvir), a hepatitis C virus (HCV) drug that, when used in combination with sofosbuvir, does not require coadministration of interferon or ribavirin for the treatment of HCV genotype 3 infections, the agency announced in a statement on July 24, 2015.

In a clinical trial, 152 treatment-naive and treatment-experienced participants with chronic HCV genotype 3 infection received Daklinza 60 mg plus sofosbuvir 400 mg once daily for 12 weeks, and were monitored for 24 weeks post treatment; 98% of the treatment-naive participants with no cirrhosis of the liver (and 58% of the treatment-naive participants with cirrhosis) achieved a sustained virologic response. Among the participants who were treatment experienced, 92% with no cirrhosis of the liver and 69% with cirrhosis achieved sustained virologic response.

“Today’s approval provides a new option for patients with genotype 3 HCV, including those patients who cannot tolerate ribavirin,” said Dr. Edward Cox, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, in a statement.

The most common side effects of Daklinza with sofosbuvir were fatigue and headache.

According to the Centers for Disease Control and Prevention, approximately 2.7 million Americans are infected with HCV of which approximately 10 percent are genotype 3.

Daklinza is marketed by Bristol-Myers Squibb, based in Princeton, N.J.

Read the full FDA statement at: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm455888.htm.

The U.S. Food and Drug Administration has approved Daklinza (daclatasvir), a hepatitis C virus (HCV) drug that, when used in combination with sofosbuvir, does not require coadministration of interferon or ribavirin for the treatment of HCV genotype 3 infections, the agency announced in a statement on July 24, 2015.

In a clinical trial, 152 treatment-naive and treatment-experienced participants with chronic HCV genotype 3 infection received Daklinza 60 mg plus sofosbuvir 400 mg once daily for 12 weeks, and were monitored for 24 weeks post treatment; 98% of the treatment-naive participants with no cirrhosis of the liver (and 58% of the treatment-naive participants with cirrhosis) achieved a sustained virologic response. Among the participants who were treatment experienced, 92% with no cirrhosis of the liver and 69% with cirrhosis achieved sustained virologic response.

“Today’s approval provides a new option for patients with genotype 3 HCV, including those patients who cannot tolerate ribavirin,” said Dr. Edward Cox, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, in a statement.

The most common side effects of Daklinza with sofosbuvir were fatigue and headache.

According to the Centers for Disease Control and Prevention, approximately 2.7 million Americans are infected with HCV of which approximately 10 percent are genotype 3.

Daklinza is marketed by Bristol-Myers Squibb, based in Princeton, N.J.

Read the full FDA statement at: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm455888.htm.

The first interferon-free treatment for people with genotype 4 hepatitis C infection has been approved by the Food and Drug Administration.

On July 24, the FDA approved a combination of three antivirals – ombitasvir, paritaprevir, and ritonavir – for use with ribavirin for treating hepatitis C virus (HCV) genotype 4 infections in people without cirrhosis, according to the agency’s statement announcing the approval. The combination tablet will be marketed as Technivie, by Abbvie. Ombitasvir is an HCV NS5A inhibitor, paritaprevir is an HCV NS3/4A protease inhibitor, and ritonavir is an HCV CYP3A inhibitor.

Technivie “is the first drug that has demonstrated safety and efficacy to treat genotype 4 HCV infections without the need for coadministration of interferon,” the statement said. It is administered orally. Technivie is a fixed-dose combination of paritaprevir/ritonavir (150/100 mg) co-formulated with ombitasvir (25 mg); it is dosed once a day and should be taken with a meal. It is co-administered with weight-based RBV (1000mg or 1200mg in divided doses, twice a day), taken with food, according to the company's statement announcing approval.

The FDA statement refers to that study of 135 people with chronic HCV genotype 4 infections and no cirrhosis, treated with the three antivirals plus ribavirin once a day for 12 weeks (91 patients), or without ribavirin (44 patients) for 12 weeks. All the patients on the three-drug combination plus ribavirin achieved a sustained virologic response (SVR12) 12 weeks after stopping treatment (no HCV detected in the blood) vs. 91% of those who did not take ribavirin. Fatigue, weakness, nausea, insomnia, pruritus and other skin reactions are among the most common adverse events associated with treatment with Technivie and ribavirin, according to the FDA statement.

The statement adds that the prescribing information includes a warning that elevations of liver enzymes up to greater than five times the upper limit of normal occurred in about 1% of the patients in clinical trials, which were more common among women taking contraceptives that contain ethinyl estradiol. Before starting treatment, women should discontinue contraceptives that containing ethinyl estradiol, and “hepatic laboratory testing should be performed during the first 4 weeks of treatment, and as clinically indicated thereafter,” the FDA statement said.

The three antivirals included in Technivie, plus dasabuvir (an HCV nonnucleoside NS5B polymerase inhibitor), are copackaged in the Viekira Pak, which was approved for the treatment of HCV genotype 1 chronic HCV infection, with or without ribavirin in 2014, and is also manufactured by Abbvie.

About 2.7 million people in the United States have chronic HCV infection, according to the Centers for Disease Control and Prevention. HCV genotype 4 is one of the least common types of HCV in the United States.


*This story was updated 7/24/2015.

emechcatie@frontlinemedcom.com

The first interferon-free treatment for people with genotype 4 hepatitis C infection has been approved by the Food and Drug Administration.

On July 24, the FDA approved a combination of three antivirals – ombitasvir, paritaprevir, and ritonavir – for use with ribavirin for treating hepatitis C virus (HCV) genotype 4 infections in people without cirrhosis, according to the agency’s statement announcing the approval. The combination tablet will be marketed as Technivie, by Abbvie. Ombitasvir is an HCV NS5A inhibitor, paritaprevir is an HCV NS3/4A protease inhibitor, and ritonavir is an HCV CYP3A inhibitor.

Technivie “is the first drug that has demonstrated safety and efficacy to treat genotype 4 HCV infections without the need for coadministration of interferon,” the statement said. It is administered orally. Technivie is a fixed-dose combination of paritaprevir/ritonavir (150/100 mg) co-formulated with ombitasvir (25 mg); it is dosed once a day and should be taken with a meal. It is co-administered with weight-based RBV (1000mg or 1200mg in divided doses, twice a day), taken with food, according to the company's statement announcing approval.

The FDA statement refers to that study of 135 people with chronic HCV genotype 4 infections and no cirrhosis, treated with the three antivirals plus ribavirin once a day for 12 weeks (91 patients), or without ribavirin (44 patients) for 12 weeks. All the patients on the three-drug combination plus ribavirin achieved a sustained virologic response (SVR12) 12 weeks after stopping treatment (no HCV detected in the blood) vs. 91% of those who did not take ribavirin. Fatigue, weakness, nausea, insomnia, pruritus and other skin reactions are among the most common adverse events associated with treatment with Technivie and ribavirin, according to the FDA statement.

The statement adds that the prescribing information includes a warning that elevations of liver enzymes up to greater than five times the upper limit of normal occurred in about 1% of the patients in clinical trials, which were more common among women taking contraceptives that contain ethinyl estradiol. Before starting treatment, women should discontinue contraceptives that containing ethinyl estradiol, and “hepatic laboratory testing should be performed during the first 4 weeks of treatment, and as clinically indicated thereafter,” the FDA statement said.

The three antivirals included in Technivie, plus dasabuvir (an HCV nonnucleoside NS5B polymerase inhibitor), are copackaged in the Viekira Pak, which was approved for the treatment of HCV genotype 1 chronic HCV infection, with or without ribavirin in 2014, and is also manufactured by Abbvie.

About 2.7 million people in the United States have chronic HCV infection, according to the Centers for Disease Control and Prevention. HCV genotype 4 is one of the least common types of HCV in the United States.


*This story was updated 7/24/2015.

emechcatie@frontlinemedcom.com

The first interferon-free treatment for people with genotype 4 hepatitis C infection has been approved by the Food and Drug Administration.

On July 24, the FDA approved a combination of three antivirals – ombitasvir, paritaprevir, and ritonavir – for use with ribavirin for treating hepatitis C virus (HCV) genotype 4 infections in people without cirrhosis, according to the agency’s statement announcing the approval. The combination tablet will be marketed as Technivie, by Abbvie. Ombitasvir is an HCV NS5A inhibitor, paritaprevir is an HCV NS3/4A protease inhibitor, and ritonavir is an HCV CYP3A inhibitor.

Technivie “is the first drug that has demonstrated safety and efficacy to treat genotype 4 HCV infections without the need for coadministration of interferon,” the statement said. It is administered orally. Technivie is a fixed-dose combination of paritaprevir/ritonavir (150/100 mg) co-formulated with ombitasvir (25 mg); it is dosed once a day and should be taken with a meal. It is co-administered with weight-based RBV (1000mg or 1200mg in divided doses, twice a day), taken with food, according to the company's statement announcing approval.

The FDA statement refers to that study of 135 people with chronic HCV genotype 4 infections and no cirrhosis, treated with the three antivirals plus ribavirin once a day for 12 weeks (91 patients), or without ribavirin (44 patients) for 12 weeks. All the patients on the three-drug combination plus ribavirin achieved a sustained virologic response (SVR12) 12 weeks after stopping treatment (no HCV detected in the blood) vs. 91% of those who did not take ribavirin. Fatigue, weakness, nausea, insomnia, pruritus and other skin reactions are among the most common adverse events associated with treatment with Technivie and ribavirin, according to the FDA statement.

The statement adds that the prescribing information includes a warning that elevations of liver enzymes up to greater than five times the upper limit of normal occurred in about 1% of the patients in clinical trials, which were more common among women taking contraceptives that contain ethinyl estradiol. Before starting treatment, women should discontinue contraceptives that containing ethinyl estradiol, and “hepatic laboratory testing should be performed during the first 4 weeks of treatment, and as clinically indicated thereafter,” the FDA statement said.

The three antivirals included in Technivie, plus dasabuvir (an HCV nonnucleoside NS5B polymerase inhibitor), are copackaged in the Viekira Pak, which was approved for the treatment of HCV genotype 1 chronic HCV infection, with or without ribavirin in 2014, and is also manufactured by Abbvie.

About 2.7 million people in the United States have chronic HCV infection, according to the Centers for Disease Control and Prevention. HCV genotype 4 is one of the least common types of HCV in the United States.


*This story was updated 7/24/2015.

emechcatie@frontlinemedcom.com

With assistance from the Centers for Disease Control and Prevention, the country of Georgia has launched a hepatitis C elimination program aimed at reducing disease transmission and meeting increased demand for diagnosis and treatment, report Dr. Kiren Mitruka and coauthors in the July 24 CDC Morbidity and Mortality Weekly Report.

Georgia has one of the world’s highest HCV prevalence rates, at 6.7%. To prepare for the launch of the program, efforts focused on describing HCV epidemiology, evaluating laboratory and health care capacity, and conducting program monitoring and evaluation, the report said.

A population-based serosurvey began in Georgia in May 2015, and seven sites have since opened to diagnose and treat HCV patients.

Results from the first phase of the program, which focused on improving access to affordable diagnostics and treatment for HCV patients with severe liver disease, found that 6,491 patients sought treatment and 6,177 (95.2%) initiated diagnostic work-up through July 3, 2015. Among these, 1,519 (24.6%) completed work-up, 1,474 (97.0%) of whom initiated treatment, the investigators reported.

Persisting challenges include the asymptomatic, chronic nature of HCV, which may result in delayed diagnosis, and ongoing transmission in health care settings and among hard to reach populations with the possibility of reinfection.

To address these obstacles, Georgia’s “comprehensive elimination plan” will cover advocacy, prevention, surveillance, testing, and access to care.

“Monitoring and evaluation will continue, and efforts are ongoing to develop an external QA/QC system to be used by laboratories to achieve and maintain biologic safety and quality diagnostic standards,” Dr. Mitruka and colleagues said.

“Georgia’s elimination program can provide information and experience that will assist similar efforts in other parts of the world,” the authors concluded.

Read the full report here: MMWR 2015 July 24.

With assistance from the Centers for Disease Control and Prevention, the country of Georgia has launched a hepatitis C elimination program aimed at reducing disease transmission and meeting increased demand for diagnosis and treatment, report Dr. Kiren Mitruka and coauthors in the July 24 CDC Morbidity and Mortality Weekly Report.

Georgia has one of the world’s highest HCV prevalence rates, at 6.7%. To prepare for the launch of the program, efforts focused on describing HCV epidemiology, evaluating laboratory and health care capacity, and conducting program monitoring and evaluation, the report said.

A population-based serosurvey began in Georgia in May 2015, and seven sites have since opened to diagnose and treat HCV patients.

Results from the first phase of the program, which focused on improving access to affordable diagnostics and treatment for HCV patients with severe liver disease, found that 6,491 patients sought treatment and 6,177 (95.2%) initiated diagnostic work-up through July 3, 2015. Among these, 1,519 (24.6%) completed work-up, 1,474 (97.0%) of whom initiated treatment, the investigators reported.

Persisting challenges include the asymptomatic, chronic nature of HCV, which may result in delayed diagnosis, and ongoing transmission in health care settings and among hard to reach populations with the possibility of reinfection.

To address these obstacles, Georgia’s “comprehensive elimination plan” will cover advocacy, prevention, surveillance, testing, and access to care.

“Monitoring and evaluation will continue, and efforts are ongoing to develop an external QA/QC system to be used by laboratories to achieve and maintain biologic safety and quality diagnostic standards,” Dr. Mitruka and colleagues said.

“Georgia’s elimination program can provide information and experience that will assist similar efforts in other parts of the world,” the authors concluded.

Read the full report here: MMWR 2015 July 24.

With assistance from the Centers for Disease Control and Prevention, the country of Georgia has launched a hepatitis C elimination program aimed at reducing disease transmission and meeting increased demand for diagnosis and treatment, report Dr. Kiren Mitruka and coauthors in the July 24 CDC Morbidity and Mortality Weekly Report.

Georgia has one of the world’s highest HCV prevalence rates, at 6.7%. To prepare for the launch of the program, efforts focused on describing HCV epidemiology, evaluating laboratory and health care capacity, and conducting program monitoring and evaluation, the report said.

A population-based serosurvey began in Georgia in May 2015, and seven sites have since opened to diagnose and treat HCV patients.

Results from the first phase of the program, which focused on improving access to affordable diagnostics and treatment for HCV patients with severe liver disease, found that 6,491 patients sought treatment and 6,177 (95.2%) initiated diagnostic work-up through July 3, 2015. Among these, 1,519 (24.6%) completed work-up, 1,474 (97.0%) of whom initiated treatment, the investigators reported.

Persisting challenges include the asymptomatic, chronic nature of HCV, which may result in delayed diagnosis, and ongoing transmission in health care settings and among hard to reach populations with the possibility of reinfection.

To address these obstacles, Georgia’s “comprehensive elimination plan” will cover advocacy, prevention, surveillance, testing, and access to care.

“Monitoring and evaluation will continue, and efforts are ongoing to develop an external QA/QC system to be used by laboratories to achieve and maintain biologic safety and quality diagnostic standards,” Dr. Mitruka and colleagues said.

“Georgia’s elimination program can provide information and experience that will assist similar efforts in other parts of the world,” the authors concluded.

Read the full report here: MMWR 2015 July 24.

Patients treated with daclatasvir and sofosbuvir for hepatitis C who are coinfected with HIV have shown a significant virologic response, regardless of whether they had already been treated for their hepatitis C infection, according to data presented at the International AIDS Society Conference on HIV Pathogenesis, Treatment & Prevention.

The open-label ALLY-2 study – published simultaneously in the July 21 online edition of the New England Journal of Medicine – in 151 previously untreated patients with hepatitis C and HIV, and 52 previously treated patients, showed 12 weeks of treatment with NS5A inhibitor daclatasvir and sofosbuvir achieved a sustained virologic response in 96.4% of untreated patients and 97.7% of previously treated patients with HCV genotype 1, with no adverse effects on HIV-1 suppression.

Among previously untreated patients treated for 8 weeks, the response rate was 75.6%, and there were no study-drug discontinuations because of adverse events (N. Engl. J. Med. 2015 July 21 [doi:10.1056/NEJMoa1503153]).

“The lower efficacy observed after 8 weeks of treatment suggests that 12 weeks of therapy may be preferred for most patients with HIV-HCV coinfection,” wrote Dr. David L. Wyles of the University of California, San Diego, and his coauthors.

Bristol-Myers Squibb supported the study. Dr. Wyles reported serving as a scientific consultant to Bristol-Myers Squibb and Gilead Sciences. Some coauthors declared grants, personal fees, and speakers fees from pharmaceutical companies, including Bristol-Myers Squibb, and several authors are employees of Bristol-Myers Squibb.

Patients treated with daclatasvir and sofosbuvir for hepatitis C who are coinfected with HIV have shown a significant virologic response, regardless of whether they had already been treated for their hepatitis C infection, according to data presented at the International AIDS Society Conference on HIV Pathogenesis, Treatment & Prevention.

The open-label ALLY-2 study – published simultaneously in the July 21 online edition of the New England Journal of Medicine – in 151 previously untreated patients with hepatitis C and HIV, and 52 previously treated patients, showed 12 weeks of treatment with NS5A inhibitor daclatasvir and sofosbuvir achieved a sustained virologic response in 96.4% of untreated patients and 97.7% of previously treated patients with HCV genotype 1, with no adverse effects on HIV-1 suppression.

Among previously untreated patients treated for 8 weeks, the response rate was 75.6%, and there were no study-drug discontinuations because of adverse events (N. Engl. J. Med. 2015 July 21 [doi:10.1056/NEJMoa1503153]).

“The lower efficacy observed after 8 weeks of treatment suggests that 12 weeks of therapy may be preferred for most patients with HIV-HCV coinfection,” wrote Dr. David L. Wyles of the University of California, San Diego, and his coauthors.

Bristol-Myers Squibb supported the study. Dr. Wyles reported serving as a scientific consultant to Bristol-Myers Squibb and Gilead Sciences. Some coauthors declared grants, personal fees, and speakers fees from pharmaceutical companies, including Bristol-Myers Squibb, and several authors are employees of Bristol-Myers Squibb.

Patients treated with daclatasvir and sofosbuvir for hepatitis C who are coinfected with HIV have shown a significant virologic response, regardless of whether they had already been treated for their hepatitis C infection, according to data presented at the International AIDS Society Conference on HIV Pathogenesis, Treatment & Prevention.

The open-label ALLY-2 study – published simultaneously in the July 21 online edition of the New England Journal of Medicine – in 151 previously untreated patients with hepatitis C and HIV, and 52 previously treated patients, showed 12 weeks of treatment with NS5A inhibitor daclatasvir and sofosbuvir achieved a sustained virologic response in 96.4% of untreated patients and 97.7% of previously treated patients with HCV genotype 1, with no adverse effects on HIV-1 suppression.

Among previously untreated patients treated for 8 weeks, the response rate was 75.6%, and there were no study-drug discontinuations because of adverse events (N. Engl. J. Med. 2015 July 21 [doi:10.1056/NEJMoa1503153]).

“The lower efficacy observed after 8 weeks of treatment suggests that 12 weeks of therapy may be preferred for most patients with HIV-HCV coinfection,” wrote Dr. David L. Wyles of the University of California, San Diego, and his coauthors.

Bristol-Myers Squibb supported the study. Dr. Wyles reported serving as a scientific consultant to Bristol-Myers Squibb and Gilead Sciences. Some coauthors declared grants, personal fees, and speakers fees from pharmaceutical companies, including Bristol-Myers Squibb, and several authors are employees of Bristol-Myers Squibb.

Treatment with ledipasvir and sofosbuvir achieves sustained virologic response at 12 weeks in patients with hepatitis C who also are infected with HIV, according to the results of the open-label ION-4 study presented at the International AIDS Society Conference on HIV Pathogenesis and Treatment.

The multicenter study in 335 patients – published simultaneously online July 21 by the New England Journal of Medicine – showed, overall, that 96% of patients had a sustained virologic response 12 weeks after the end of therapy, while the response rates were higher (100%) among individuals with HCV genotype 4 but lower in black patients.

“This association between black race and a decreased rate of virologic response was not observed in the 308 black patients who were monoinfected with HCV receiving ledipasvir-sofosbuvir across the phase III program,” wrote Dr. Susanna Naggie of the Duke Clinical Research Institute, Durham, N.C., and her coauthors.

Response rates were not influenced by previous treatments or the presence of cirrhosis, and while there were some adverse events such as headache, fatigue, and diarrhea, no patient had confirmed HIV-1 virologic rebound (N. Engl. J. Med. 2015 July 21 [doi:10.1056/NEJMoa1501315]).

The study was supported by Gilead Sciences. Some authors declared grants, support, advisory board positions, and consultancies from pharmaceutical companies, including Gilead Sciences, and several authors are employees of Gilead Sciences.

Treatment with ledipasvir and sofosbuvir achieves sustained virologic response at 12 weeks in patients with hepatitis C who also are infected with HIV, according to the results of the open-label ION-4 study presented at the International AIDS Society Conference on HIV Pathogenesis and Treatment.

The multicenter study in 335 patients – published simultaneously online July 21 by the New England Journal of Medicine – showed, overall, that 96% of patients had a sustained virologic response 12 weeks after the end of therapy, while the response rates were higher (100%) among individuals with HCV genotype 4 but lower in black patients.

“This association between black race and a decreased rate of virologic response was not observed in the 308 black patients who were monoinfected with HCV receiving ledipasvir-sofosbuvir across the phase III program,” wrote Dr. Susanna Naggie of the Duke Clinical Research Institute, Durham, N.C., and her coauthors.

Response rates were not influenced by previous treatments or the presence of cirrhosis, and while there were some adverse events such as headache, fatigue, and diarrhea, no patient had confirmed HIV-1 virologic rebound (N. Engl. J. Med. 2015 July 21 [doi:10.1056/NEJMoa1501315]).

The study was supported by Gilead Sciences. Some authors declared grants, support, advisory board positions, and consultancies from pharmaceutical companies, including Gilead Sciences, and several authors are employees of Gilead Sciences.

Treatment with ledipasvir and sofosbuvir achieves sustained virologic response at 12 weeks in patients with hepatitis C who also are infected with HIV, according to the results of the open-label ION-4 study presented at the International AIDS Society Conference on HIV Pathogenesis and Treatment.

The multicenter study in 335 patients – published simultaneously online July 21 by the New England Journal of Medicine – showed, overall, that 96% of patients had a sustained virologic response 12 weeks after the end of therapy, while the response rates were higher (100%) among individuals with HCV genotype 4 but lower in black patients.

“This association between black race and a decreased rate of virologic response was not observed in the 308 black patients who were monoinfected with HCV receiving ledipasvir-sofosbuvir across the phase III program,” wrote Dr. Susanna Naggie of the Duke Clinical Research Institute, Durham, N.C., and her coauthors.

Response rates were not influenced by previous treatments or the presence of cirrhosis, and while there were some adverse events such as headache, fatigue, and diarrhea, no patient had confirmed HIV-1 virologic rebound (N. Engl. J. Med. 2015 July 21 [doi:10.1056/NEJMoa1501315]).

The study was supported by Gilead Sciences. Some authors declared grants, support, advisory board positions, and consultancies from pharmaceutical companies, including Gilead Sciences, and several authors are employees of Gilead Sciences.

WASHINGTON – An investigational once-daily antiviral drug combination produced high rates of sustained viral responses after 12 or 16 weeks of therapy – with or without ribavirin – in patients with chronic hepatitis viral infections for whom prior therapy with peg-interferon and ribavirin had failed, investigators reported.

The rate of sustained viral responses at 12 weeks after the end of treatment (SVR12) was 92% for patients who received the combination of grazoprevir and elbasvir (GZR/EBR, Merck) alone, compared with 94% for patients who received the antivirals plus ribavirin, reported Dr. Paul Kwo of Indiana University Hospital in Indianapolis.

Among patients who received 16 weeks of therapy, the SVR12 rates were 92% without ribavirin, and 97% with ribavirin, Dr. Kwo said at the annual Digestive Disease Week.

“In patients who have failed peg-interferon and ribavirin therapy, 12 weeks of grazoprevir and elbasvir without ribavirin gives outstanding SVR rates in genotype 1b-infected individuals, regardless of treatment response, including those with cirrhosis. If you’re a relapser with genotype 1a or genotype 4 infection, 12 weeks of grazoprevir and elbasvir gives outstanding SVR rates. For genotype 1a, 4 and 6 prior null and partial responders, including those with cirrhosis, 16 weeks of grazoprevir and elbasvir with ribavirin gives outstanding SVR rates with no virologic failures,” he said.

Dr. Kwo presented updated results from the C-EDGE(Study of Efficacy and Safety of Grazoprevir (MK-5172)/Elbasvir (MK-8742) Combination Regimen for Treatment-Naive Participants With Chronic Hepatitis C Virus Genotypes 1, 4, and 6) treatment-experienced trial.

The 12-week C-EDGE results in 316 treatment-naive patients were presented earlier this year in Vienna at the International Liver Congress.

The fixed-dose, once-daily combination is composed of grazoprevir, an inhibitor of the HCV NS3/4a protease, at a dose of 100 mg, and elbasvir, a potent inhibitor of the NS5a protein, at a dose of 50 mg. This combination was shown to have broad activity against most HCV genotypes in vitro, and was efficacious in both treatment-naive and treatment-experienced patients with and without cirrhosis, including those with HIV/HCV coinfections, in the C-WORTHY trial.

The C-EDGE study was a phase III trial of GZR/EBR with or without ribavirin for 12 or 16 weeks for patients for whom prior therapy with peg-interferon and ribavirin had failed because of either null or partial response or viral relapse. The trial included patients with and without cirrhosis, those with HCV genotypes 1, 4, or 6, and those with either HCV mono-infections or HIV coinfections.

A total of 420 patients were enrolled.

As noted before, 97 of 105 patients (92%) on 12 weeks of therapy without ribavirin had an SVR12, although two patients in this group were lost to follow-up or discontinued therapy for reasons other than virologic failure (included as nonresponders). Among patients who received 12 weeks of GZR/EBR plus ribavirin, 98 of 104 (94%) had an SVR12, with no losses to follow-up.

For those patients treated for 16 weeks, 97 of 105 (92%) without ribavirin had an SVR12, compared with 103 of 106 (97%) who received ribavirin in addition to the combination antivirals. In these groups, one and three patients, respectively, were lost to follow-up.

In a subanalysis by HCV genotype or subtype, the combination alone was least effective among patients with genotype 4 treated for 16 weeks, with 3 of 5 patients (60%) having an SVR12, compared with 7 of 9 patients (79%) with genotype 4 treated with no ribavirin for 12 weeks, 14 of 15 (93%) with ribavirin for 12 weeks, and 8 of 8 (100%) treated with ribavirin for 16 weeks. The overall numbers of patients in each subgroup was too small for statistical significance analysis, however.

Among patients with HCV coinfection, the SVR12 rate was 100% in all treatment arms except 16 weeks GZR/EBR without ribavirin (5 of 6; 83%).

A subanalysis by prior response, excluding the 12 total patients who did not complete treatment, showed excellent SVR12 rates in all four treatment arms among patients with a prior relapse, and slightly less robust but still high rates among prior partial or null responders, Dr. Kwo said.

Patients tolerated the regimen well, with the rates of serious adverse events ranging from 2.9% to 3.8%. There were no deaths, and seven discontinuations due to adverse events (one in each in the 12-week arms, and five in the 16-week with ribavirin arm). A total of 31 patients who received ribavirin had hemoglobin reductions below 10 g/dL, and 60 reported fatigue, both common with ribavirin. The majority of adverse events in all arms were fatigue, headache, and nausea.

The combination has received two Breakthrough Therapy designations from the Food and Drug Administration for patients with HCV genotype 4, and for patients with genotype 1 infections who are on hemodialysis for end stage renal disease. The breakthrough designation makes the drug eligible for expedited review.

Dr. Kwo disclosed ties with Merck, which supported the C-EDGE study.

WASHINGTON – An investigational once-daily antiviral drug combination produced high rates of sustained viral responses after 12 or 16 weeks of therapy – with or without ribavirin – in patients with chronic hepatitis viral infections for whom prior therapy with peg-interferon and ribavirin had failed, investigators reported.

The rate of sustained viral responses at 12 weeks after the end of treatment (SVR12) was 92% for patients who received the combination of grazoprevir and elbasvir (GZR/EBR, Merck) alone, compared with 94% for patients who received the antivirals plus ribavirin, reported Dr. Paul Kwo of Indiana University Hospital in Indianapolis.

Among patients who received 16 weeks of therapy, the SVR12 rates were 92% without ribavirin, and 97% with ribavirin, Dr. Kwo said at the annual Digestive Disease Week.

“In patients who have failed peg-interferon and ribavirin therapy, 12 weeks of grazoprevir and elbasvir without ribavirin gives outstanding SVR rates in genotype 1b-infected individuals, regardless of treatment response, including those with cirrhosis. If you’re a relapser with genotype 1a or genotype 4 infection, 12 weeks of grazoprevir and elbasvir gives outstanding SVR rates. For genotype 1a, 4 and 6 prior null and partial responders, including those with cirrhosis, 16 weeks of grazoprevir and elbasvir with ribavirin gives outstanding SVR rates with no virologic failures,” he said.

Dr. Kwo presented updated results from the C-EDGE(Study of Efficacy and Safety of Grazoprevir (MK-5172)/Elbasvir (MK-8742) Combination Regimen for Treatment-Naive Participants With Chronic Hepatitis C Virus Genotypes 1, 4, and 6) treatment-experienced trial.

The 12-week C-EDGE results in 316 treatment-naive patients were presented earlier this year in Vienna at the International Liver Congress.

The fixed-dose, once-daily combination is composed of grazoprevir, an inhibitor of the HCV NS3/4a protease, at a dose of 100 mg, and elbasvir, a potent inhibitor of the NS5a protein, at a dose of 50 mg. This combination was shown to have broad activity against most HCV genotypes in vitro, and was efficacious in both treatment-naive and treatment-experienced patients with and without cirrhosis, including those with HIV/HCV coinfections, in the C-WORTHY trial.

The C-EDGE study was a phase III trial of GZR/EBR with or without ribavirin for 12 or 16 weeks for patients for whom prior therapy with peg-interferon and ribavirin had failed because of either null or partial response or viral relapse. The trial included patients with and without cirrhosis, those with HCV genotypes 1, 4, or 6, and those with either HCV mono-infections or HIV coinfections.

A total of 420 patients were enrolled.

As noted before, 97 of 105 patients (92%) on 12 weeks of therapy without ribavirin had an SVR12, although two patients in this group were lost to follow-up or discontinued therapy for reasons other than virologic failure (included as nonresponders). Among patients who received 12 weeks of GZR/EBR plus ribavirin, 98 of 104 (94%) had an SVR12, with no losses to follow-up.

For those patients treated for 16 weeks, 97 of 105 (92%) without ribavirin had an SVR12, compared with 103 of 106 (97%) who received ribavirin in addition to the combination antivirals. In these groups, one and three patients, respectively, were lost to follow-up.

In a subanalysis by HCV genotype or subtype, the combination alone was least effective among patients with genotype 4 treated for 16 weeks, with 3 of 5 patients (60%) having an SVR12, compared with 7 of 9 patients (79%) with genotype 4 treated with no ribavirin for 12 weeks, 14 of 15 (93%) with ribavirin for 12 weeks, and 8 of 8 (100%) treated with ribavirin for 16 weeks. The overall numbers of patients in each subgroup was too small for statistical significance analysis, however.

Among patients with HCV coinfection, the SVR12 rate was 100% in all treatment arms except 16 weeks GZR/EBR without ribavirin (5 of 6; 83%).

A subanalysis by prior response, excluding the 12 total patients who did not complete treatment, showed excellent SVR12 rates in all four treatment arms among patients with a prior relapse, and slightly less robust but still high rates among prior partial or null responders, Dr. Kwo said.

Patients tolerated the regimen well, with the rates of serious adverse events ranging from 2.9% to 3.8%. There were no deaths, and seven discontinuations due to adverse events (one in each in the 12-week arms, and five in the 16-week with ribavirin arm). A total of 31 patients who received ribavirin had hemoglobin reductions below 10 g/dL, and 60 reported fatigue, both common with ribavirin. The majority of adverse events in all arms were fatigue, headache, and nausea.

The combination has received two Breakthrough Therapy designations from the Food and Drug Administration for patients with HCV genotype 4, and for patients with genotype 1 infections who are on hemodialysis for end stage renal disease. The breakthrough designation makes the drug eligible for expedited review.

Dr. Kwo disclosed ties with Merck, which supported the C-EDGE study.

WASHINGTON – An investigational once-daily antiviral drug combination produced high rates of sustained viral responses after 12 or 16 weeks of therapy – with or without ribavirin – in patients with chronic hepatitis viral infections for whom prior therapy with peg-interferon and ribavirin had failed, investigators reported.

The rate of sustained viral responses at 12 weeks after the end of treatment (SVR12) was 92% for patients who received the combination of grazoprevir and elbasvir (GZR/EBR, Merck) alone, compared with 94% for patients who received the antivirals plus ribavirin, reported Dr. Paul Kwo of Indiana University Hospital in Indianapolis.

Among patients who received 16 weeks of therapy, the SVR12 rates were 92% without ribavirin, and 97% with ribavirin, Dr. Kwo said at the annual Digestive Disease Week.

“In patients who have failed peg-interferon and ribavirin therapy, 12 weeks of grazoprevir and elbasvir without ribavirin gives outstanding SVR rates in genotype 1b-infected individuals, regardless of treatment response, including those with cirrhosis. If you’re a relapser with genotype 1a or genotype 4 infection, 12 weeks of grazoprevir and elbasvir gives outstanding SVR rates. For genotype 1a, 4 and 6 prior null and partial responders, including those with cirrhosis, 16 weeks of grazoprevir and elbasvir with ribavirin gives outstanding SVR rates with no virologic failures,” he said.

Dr. Kwo presented updated results from the C-EDGE(Study of Efficacy and Safety of Grazoprevir (MK-5172)/Elbasvir (MK-8742) Combination Regimen for Treatment-Naive Participants With Chronic Hepatitis C Virus Genotypes 1, 4, and 6) treatment-experienced trial.

The 12-week C-EDGE results in 316 treatment-naive patients were presented earlier this year in Vienna at the International Liver Congress.

The fixed-dose, once-daily combination is composed of grazoprevir, an inhibitor of the HCV NS3/4a protease, at a dose of 100 mg, and elbasvir, a potent inhibitor of the NS5a protein, at a dose of 50 mg. This combination was shown to have broad activity against most HCV genotypes in vitro, and was efficacious in both treatment-naive and treatment-experienced patients with and without cirrhosis, including those with HIV/HCV coinfections, in the C-WORTHY trial.

The C-EDGE study was a phase III trial of GZR/EBR with or without ribavirin for 12 or 16 weeks for patients for whom prior therapy with peg-interferon and ribavirin had failed because of either null or partial response or viral relapse. The trial included patients with and without cirrhosis, those with HCV genotypes 1, 4, or 6, and those with either HCV mono-infections or HIV coinfections.

A total of 420 patients were enrolled.

As noted before, 97 of 105 patients (92%) on 12 weeks of therapy without ribavirin had an SVR12, although two patients in this group were lost to follow-up or discontinued therapy for reasons other than virologic failure (included as nonresponders). Among patients who received 12 weeks of GZR/EBR plus ribavirin, 98 of 104 (94%) had an SVR12, with no losses to follow-up.

For those patients treated for 16 weeks, 97 of 105 (92%) without ribavirin had an SVR12, compared with 103 of 106 (97%) who received ribavirin in addition to the combination antivirals. In these groups, one and three patients, respectively, were lost to follow-up.

In a subanalysis by HCV genotype or subtype, the combination alone was least effective among patients with genotype 4 treated for 16 weeks, with 3 of 5 patients (60%) having an SVR12, compared with 7 of 9 patients (79%) with genotype 4 treated with no ribavirin for 12 weeks, 14 of 15 (93%) with ribavirin for 12 weeks, and 8 of 8 (100%) treated with ribavirin for 16 weeks. The overall numbers of patients in each subgroup was too small for statistical significance analysis, however.

Among patients with HCV coinfection, the SVR12 rate was 100% in all treatment arms except 16 weeks GZR/EBR without ribavirin (5 of 6; 83%).

A subanalysis by prior response, excluding the 12 total patients who did not complete treatment, showed excellent SVR12 rates in all four treatment arms among patients with a prior relapse, and slightly less robust but still high rates among prior partial or null responders, Dr. Kwo said.

Patients tolerated the regimen well, with the rates of serious adverse events ranging from 2.9% to 3.8%. There were no deaths, and seven discontinuations due to adverse events (one in each in the 12-week arms, and five in the 16-week with ribavirin arm). A total of 31 patients who received ribavirin had hemoglobin reductions below 10 g/dL, and 60 reported fatigue, both common with ribavirin. The majority of adverse events in all arms were fatigue, headache, and nausea.

The combination has received two Breakthrough Therapy designations from the Food and Drug Administration for patients with HCV genotype 4, and for patients with genotype 1 infections who are on hemodialysis for end stage renal disease. The breakthrough designation makes the drug eligible for expedited review.

Dr. Kwo disclosed ties with Merck, which supported the C-EDGE study.