HCV Hub

A simulation model that incorporated a one-time universal screening of U.S. adults for hepatitis C virus and made conservative assumptions as to the availability and efficacy of various therapies projected that the infection could become rare by 2026, according to a report published online Aug. 4 in the Annals of Internal Medicine.

Treatment for HCV has evolved rapidly during the past 20 years, and new therapies being developed now show the potential to increase response rates even further, reduce treatment duration, and improve safety profiles. In light of these advances, researchers devised a computerized simulation model to project what the burden of HCV disease has been and will be for the years 2001-2050 in the United States, said Mina Kabiri of the University of Pittsburgh Graduate School of Public Health and her associates.

©Pearl Jackson/iStockphoto.com

The investigators analyzed information in national databases to form baseline assumptions about infection rates, the prevalences of each disease stage, treatment responses, and the medical system’s treatment capacity, and they attempted to adjust for the introduction of new therapies over time. They made a conservative estimate that over time, rates of sustained virologic response would average 90% in real world practice, even though rates as high as 97% have already been reported in clinical trials of currently available treatments. And they incorporated a one-time-only screening of all adults for occult HCV infection, on the assumption that most of those identified would seek treatment, which would head off the development of HCV-related diseases such as hepatocellular carcinoma. Finally, Ms. Kabiri and her associates validated their model by applying it in several published study cohorts and finding that their projections accorded with the actual results of those studies.

The model projected that under base-case assumptions, HCV infection would become rare by 2036, affecting only 1 in 1,500 persons, and that under best-case assumptions HCV could become rare by 2026. "The ideal scenario could reduce the total number of cases of [HCV-related] decompensated cirrhosis by 135,800 cases (46%), cases of hepatocellular carcinoma by 96,300 (40%), liver-related deaths by 161,500 (37%), and liver transplantations by 13,900 (37%) during 2014-2050," the researchers wrote (Ann. Intern. Med. 2014 Aug. 4 [doi:10.7326/M14-0095]).

Increasing the medical system’s capacity to treat HCV would further reduce the burden of disease. "With the launch of all-oral drugs that can simplify treatment, primary care physicians or infectious disease specialists also may take on the role of treating patients with HCV infection, thus alleviating the burden on hepatologists," the investigators noted.

This study was supported by the National Center for Advancing Translational Sciences at the National Institutes of Health and by the University of Pittsburgh Graduate School of Public Health.

A simulation model that incorporated a one-time universal screening of U.S. adults for hepatitis C virus and made conservative assumptions as to the availability and efficacy of various therapies projected that the infection could become rare by 2026, according to a report published online Aug. 4 in the Annals of Internal Medicine.

Treatment for HCV has evolved rapidly during the past 20 years, and new therapies being developed now show the potential to increase response rates even further, reduce treatment duration, and improve safety profiles. In light of these advances, researchers devised a computerized simulation model to project what the burden of HCV disease has been and will be for the years 2001-2050 in the United States, said Mina Kabiri of the University of Pittsburgh Graduate School of Public Health and her associates.

©Pearl Jackson/iStockphoto.com

The investigators analyzed information in national databases to form baseline assumptions about infection rates, the prevalences of each disease stage, treatment responses, and the medical system’s treatment capacity, and they attempted to adjust for the introduction of new therapies over time. They made a conservative estimate that over time, rates of sustained virologic response would average 90% in real world practice, even though rates as high as 97% have already been reported in clinical trials of currently available treatments. And they incorporated a one-time-only screening of all adults for occult HCV infection, on the assumption that most of those identified would seek treatment, which would head off the development of HCV-related diseases such as hepatocellular carcinoma. Finally, Ms. Kabiri and her associates validated their model by applying it in several published study cohorts and finding that their projections accorded with the actual results of those studies.

The model projected that under base-case assumptions, HCV infection would become rare by 2036, affecting only 1 in 1,500 persons, and that under best-case assumptions HCV could become rare by 2026. "The ideal scenario could reduce the total number of cases of [HCV-related] decompensated cirrhosis by 135,800 cases (46%), cases of hepatocellular carcinoma by 96,300 (40%), liver-related deaths by 161,500 (37%), and liver transplantations by 13,900 (37%) during 2014-2050," the researchers wrote (Ann. Intern. Med. 2014 Aug. 4 [doi:10.7326/M14-0095]).

Increasing the medical system’s capacity to treat HCV would further reduce the burden of disease. "With the launch of all-oral drugs that can simplify treatment, primary care physicians or infectious disease specialists also may take on the role of treating patients with HCV infection, thus alleviating the burden on hepatologists," the investigators noted.

This study was supported by the National Center for Advancing Translational Sciences at the National Institutes of Health and by the University of Pittsburgh Graduate School of Public Health.

A simulation model that incorporated a one-time universal screening of U.S. adults for hepatitis C virus and made conservative assumptions as to the availability and efficacy of various therapies projected that the infection could become rare by 2026, according to a report published online Aug. 4 in the Annals of Internal Medicine.

Treatment for HCV has evolved rapidly during the past 20 years, and new therapies being developed now show the potential to increase response rates even further, reduce treatment duration, and improve safety profiles. In light of these advances, researchers devised a computerized simulation model to project what the burden of HCV disease has been and will be for the years 2001-2050 in the United States, said Mina Kabiri of the University of Pittsburgh Graduate School of Public Health and her associates.

©Pearl Jackson/iStockphoto.com

The investigators analyzed information in national databases to form baseline assumptions about infection rates, the prevalences of each disease stage, treatment responses, and the medical system’s treatment capacity, and they attempted to adjust for the introduction of new therapies over time. They made a conservative estimate that over time, rates of sustained virologic response would average 90% in real world practice, even though rates as high as 97% have already been reported in clinical trials of currently available treatments. And they incorporated a one-time-only screening of all adults for occult HCV infection, on the assumption that most of those identified would seek treatment, which would head off the development of HCV-related diseases such as hepatocellular carcinoma. Finally, Ms. Kabiri and her associates validated their model by applying it in several published study cohorts and finding that their projections accorded with the actual results of those studies.

The model projected that under base-case assumptions, HCV infection would become rare by 2036, affecting only 1 in 1,500 persons, and that under best-case assumptions HCV could become rare by 2026. "The ideal scenario could reduce the total number of cases of [HCV-related] decompensated cirrhosis by 135,800 cases (46%), cases of hepatocellular carcinoma by 96,300 (40%), liver-related deaths by 161,500 (37%), and liver transplantations by 13,900 (37%) during 2014-2050," the researchers wrote (Ann. Intern. Med. 2014 Aug. 4 [doi:10.7326/M14-0095]).

Increasing the medical system’s capacity to treat HCV would further reduce the burden of disease. "With the launch of all-oral drugs that can simplify treatment, primary care physicians or infectious disease specialists also may take on the role of treating patients with HCV infection, thus alleviating the burden on hepatologists," the investigators noted.

This study was supported by the National Center for Advancing Translational Sciences at the National Institutes of Health and by the University of Pittsburgh Graduate School of Public Health.

Two interferon-free combination therapies yielded sustained virologic responses of 96%-100% in an international, open-label, phase III, randomized trial involving 186 patients with refractory hepatitis C virus type 1b infection, Dr. Pietro Andreone and his colleagues reported in the August 2014 issue of Gastroenterology (doi:org/10.1053/j.gastro.2014.04.037).

Twelve weeks of treatment using the combination regimen plus ribavirin (91 patients) or the same regimen without ribavirin (95 patients) produced sustained virologic responses (SVRs) that were noninferior to historic SVRs reported in the literature for comparable patients treated with telaprevir plus pegylated-interferon plus ribavirin.

Source: American Gastroenterological Institute

None of the patients taking the new combination regimen experienced virologic failure while taking the drugs or relapse during the year after completing treatment. And adverse effects were characterized as "generally mild and manageable," said Dr. Andreone of the department of medical science and surgery, University of Bologna (Italy), and his associates.

HCV type 1b is the most prevalent genotype worldwide. Patients with this genotype who have failed on standard treatments "have not been extensively studied with currently approved or investigational interferon-free regimens, hence this large patient population represents a group with unmet need," the investigators noted.

They assessed such patients at 43 medical centers in Austria, Belgium, Italy, the Netherlands, Portugal, Puerto Rico, Sweden, Switzerland, Turkey, and the United States. All were aged between 18 and 70 years, and all were free of cirrhosis and coinfections.

The daily oral combination regimen consisted of ABT-450, a protease inhibitor that has shown in-vitro antiviral activity; ritonavir, a CYP3A4 inhibitor that enables once-daily rather than more frequent dosing of the ABT-450; ombitasvir, an HCV NS5A inhibitor; and dasabuvir, an HCV NS5B RNA nonnucleoside polymerase inhibitor.

The primary efficacy endpoint was an SVR rate noninferior to the historical rate for interferon-containing regimens in comparable patients. In the intention-to-treat analysis, the SVRs met and surpassed that standard, at 96.6% for ABT-450/ritonavir/ombitasvir/dasabuvir plus ribavirin and 100% for ABT-450/ritonavir/ombitasvir/dasabuvir without ribavirin.

Moreover, of the three patients who did not achieve a sustained virologic response, two had discontinued the study drug because of adverse events and one was lost to follow-up after only 4 weeks of treatment.

The most common adverse events were fatigue, headache, and nausea, all of which were significantly more frequent among patients taking ribavirin. Insomnia, anemia, rash, and elevated bilirubin also were related to ribavirin and were easily managed.

Only two patients discontinued treatment due to adverse events, neither of which were considered to be related to a study drug. One patient developed pancreatitis and another developed anxiety, tachycardia, and dyspnea.

Three other serious adverse events – cellulitis, nephrolithiasis, and osteoarthritis – also were judged to be unrelated to the study treatments.

Declines in hemoglobin levels occurred in 42% of the patients who received ribavirin but only 5.5% of those who did not. However, clinically significant declines occurred in only two patients, and neither of them required transfusions or erythropoietin.

Their findings show that 12 weeks of combined oral ABT-450/ritonavir/ombitasvir/dasabuvir therapy without ribavirin is at least as effective as interferon-containing regimens, and it produces significantly fewer and less severe adverse effects, the investigators said.

This study was somewhat limited in that it used an open-label design and did not include patients with concomitant cirrhosis, hepatitis B viral infection, or HIV infection, they added.

This study was sponsored by AbbVie, which also participated in the study design, data collection and analysis, and manuscript preparation. Dr. Andreone reported receiving research support from, being a consultant for, or serving on advisory committees for Roche, Merck, Gilead Sciences, Janssen Cilag, AbbVie, Boehringer Ingelheim, and BMS; his associates reported ties to numerous industry sources.

Two interferon-free combination therapies yielded sustained virologic responses of 96%-100% in an international, open-label, phase III, randomized trial involving 186 patients with refractory hepatitis C virus type 1b infection, Dr. Pietro Andreone and his colleagues reported in the August 2014 issue of Gastroenterology (doi:org/10.1053/j.gastro.2014.04.037).

Twelve weeks of treatment using the combination regimen plus ribavirin (91 patients) or the same regimen without ribavirin (95 patients) produced sustained virologic responses (SVRs) that were noninferior to historic SVRs reported in the literature for comparable patients treated with telaprevir plus pegylated-interferon plus ribavirin.

Source: American Gastroenterological Institute

None of the patients taking the new combination regimen experienced virologic failure while taking the drugs or relapse during the year after completing treatment. And adverse effects were characterized as "generally mild and manageable," said Dr. Andreone of the department of medical science and surgery, University of Bologna (Italy), and his associates.

HCV type 1b is the most prevalent genotype worldwide. Patients with this genotype who have failed on standard treatments "have not been extensively studied with currently approved or investigational interferon-free regimens, hence this large patient population represents a group with unmet need," the investigators noted.

They assessed such patients at 43 medical centers in Austria, Belgium, Italy, the Netherlands, Portugal, Puerto Rico, Sweden, Switzerland, Turkey, and the United States. All were aged between 18 and 70 years, and all were free of cirrhosis and coinfections.

The daily oral combination regimen consisted of ABT-450, a protease inhibitor that has shown in-vitro antiviral activity; ritonavir, a CYP3A4 inhibitor that enables once-daily rather than more frequent dosing of the ABT-450; ombitasvir, an HCV NS5A inhibitor; and dasabuvir, an HCV NS5B RNA nonnucleoside polymerase inhibitor.

The primary efficacy endpoint was an SVR rate noninferior to the historical rate for interferon-containing regimens in comparable patients. In the intention-to-treat analysis, the SVRs met and surpassed that standard, at 96.6% for ABT-450/ritonavir/ombitasvir/dasabuvir plus ribavirin and 100% for ABT-450/ritonavir/ombitasvir/dasabuvir without ribavirin.

Moreover, of the three patients who did not achieve a sustained virologic response, two had discontinued the study drug because of adverse events and one was lost to follow-up after only 4 weeks of treatment.

The most common adverse events were fatigue, headache, and nausea, all of which were significantly more frequent among patients taking ribavirin. Insomnia, anemia, rash, and elevated bilirubin also were related to ribavirin and were easily managed.

Only two patients discontinued treatment due to adverse events, neither of which were considered to be related to a study drug. One patient developed pancreatitis and another developed anxiety, tachycardia, and dyspnea.

Three other serious adverse events – cellulitis, nephrolithiasis, and osteoarthritis – also were judged to be unrelated to the study treatments.

Declines in hemoglobin levels occurred in 42% of the patients who received ribavirin but only 5.5% of those who did not. However, clinically significant declines occurred in only two patients, and neither of them required transfusions or erythropoietin.

Their findings show that 12 weeks of combined oral ABT-450/ritonavir/ombitasvir/dasabuvir therapy without ribavirin is at least as effective as interferon-containing regimens, and it produces significantly fewer and less severe adverse effects, the investigators said.

This study was somewhat limited in that it used an open-label design and did not include patients with concomitant cirrhosis, hepatitis B viral infection, or HIV infection, they added.

This study was sponsored by AbbVie, which also participated in the study design, data collection and analysis, and manuscript preparation. Dr. Andreone reported receiving research support from, being a consultant for, or serving on advisory committees for Roche, Merck, Gilead Sciences, Janssen Cilag, AbbVie, Boehringer Ingelheim, and BMS; his associates reported ties to numerous industry sources.

Two interferon-free combination therapies yielded sustained virologic responses of 96%-100% in an international, open-label, phase III, randomized trial involving 186 patients with refractory hepatitis C virus type 1b infection, Dr. Pietro Andreone and his colleagues reported in the August 2014 issue of Gastroenterology (doi:org/10.1053/j.gastro.2014.04.037).

Twelve weeks of treatment using the combination regimen plus ribavirin (91 patients) or the same regimen without ribavirin (95 patients) produced sustained virologic responses (SVRs) that were noninferior to historic SVRs reported in the literature for comparable patients treated with telaprevir plus pegylated-interferon plus ribavirin.

Source: American Gastroenterological Institute

None of the patients taking the new combination regimen experienced virologic failure while taking the drugs or relapse during the year after completing treatment. And adverse effects were characterized as "generally mild and manageable," said Dr. Andreone of the department of medical science and surgery, University of Bologna (Italy), and his associates.

HCV type 1b is the most prevalent genotype worldwide. Patients with this genotype who have failed on standard treatments "have not been extensively studied with currently approved or investigational interferon-free regimens, hence this large patient population represents a group with unmet need," the investigators noted.

They assessed such patients at 43 medical centers in Austria, Belgium, Italy, the Netherlands, Portugal, Puerto Rico, Sweden, Switzerland, Turkey, and the United States. All were aged between 18 and 70 years, and all were free of cirrhosis and coinfections.

The daily oral combination regimen consisted of ABT-450, a protease inhibitor that has shown in-vitro antiviral activity; ritonavir, a CYP3A4 inhibitor that enables once-daily rather than more frequent dosing of the ABT-450; ombitasvir, an HCV NS5A inhibitor; and dasabuvir, an HCV NS5B RNA nonnucleoside polymerase inhibitor.

The primary efficacy endpoint was an SVR rate noninferior to the historical rate for interferon-containing regimens in comparable patients. In the intention-to-treat analysis, the SVRs met and surpassed that standard, at 96.6% for ABT-450/ritonavir/ombitasvir/dasabuvir plus ribavirin and 100% for ABT-450/ritonavir/ombitasvir/dasabuvir without ribavirin.

Moreover, of the three patients who did not achieve a sustained virologic response, two had discontinued the study drug because of adverse events and one was lost to follow-up after only 4 weeks of treatment.

The most common adverse events were fatigue, headache, and nausea, all of which were significantly more frequent among patients taking ribavirin. Insomnia, anemia, rash, and elevated bilirubin also were related to ribavirin and were easily managed.

Only two patients discontinued treatment due to adverse events, neither of which were considered to be related to a study drug. One patient developed pancreatitis and another developed anxiety, tachycardia, and dyspnea.

Three other serious adverse events – cellulitis, nephrolithiasis, and osteoarthritis – also were judged to be unrelated to the study treatments.

Declines in hemoglobin levels occurred in 42% of the patients who received ribavirin but only 5.5% of those who did not. However, clinically significant declines occurred in only two patients, and neither of them required transfusions or erythropoietin.

Their findings show that 12 weeks of combined oral ABT-450/ritonavir/ombitasvir/dasabuvir therapy without ribavirin is at least as effective as interferon-containing regimens, and it produces significantly fewer and less severe adverse effects, the investigators said.

This study was somewhat limited in that it used an open-label design and did not include patients with concomitant cirrhosis, hepatitis B viral infection, or HIV infection, they added.

This study was sponsored by AbbVie, which also participated in the study design, data collection and analysis, and manuscript preparation. Dr. Andreone reported receiving research support from, being a consultant for, or serving on advisory committees for Roche, Merck, Gilead Sciences, Janssen Cilag, AbbVie, Boehringer Ingelheim, and BMS; his associates reported ties to numerous industry sources.

New treatments for hepatitis C could boost federal spending for the Medicare Part D program by up to $5.8 billion in 2015 and lead to a 4.3%-8.6% premium increase for beneficiaries, according to a report by the actuarial firm Milliman, prepared for the Pharmaceutical Care Management Association.

Milliman examined the cost impact of sofosbuvir, marketed by Gilead Sciences as Sovaldi; the drug was approved by the Food and Drug Administration in December 2013 and carries an $84,000 price tag for a 12-week treatment regimen.

"Unlike some other high-cost specialty drugs, the new HCV [hepatitis C virus] drugs have a significant patient base, so their financial impact causes a meaningful and measurable increase in costs to beneficiaries and United States taxpayers," the report said. "No one knows for sure how many infected beneficiaries will ultimately receive the new treatment, but if for example, 50% of infected Medicare Part D beneficiaries were eventually treated with the $84,000 course of treatment, approximately $11 billion of new spending would enter the Part D system."

The report noted that hepatitis C is more prevalent among low-income individuals, placing an additional cost burden on the government, as these people are either covered by Medicaid or dually eligible for Medicare and Medicaid.

Milliman based its findings on the cost of taking sofosbuvir for 12 weeks, but noted that the "relative use pattern for these drugs is not well established." The analysis does not reflect any potential cost savings from reductions in other medical costs (such as treating chronic liver disease), which may result from using one of these new drugs.

gtwachtman@frontlinemedcom.com

New treatments for hepatitis C could boost federal spending for the Medicare Part D program by up to $5.8 billion in 2015 and lead to a 4.3%-8.6% premium increase for beneficiaries, according to a report by the actuarial firm Milliman, prepared for the Pharmaceutical Care Management Association.

Milliman examined the cost impact of sofosbuvir, marketed by Gilead Sciences as Sovaldi; the drug was approved by the Food and Drug Administration in December 2013 and carries an $84,000 price tag for a 12-week treatment regimen.

"Unlike some other high-cost specialty drugs, the new HCV [hepatitis C virus] drugs have a significant patient base, so their financial impact causes a meaningful and measurable increase in costs to beneficiaries and United States taxpayers," the report said. "No one knows for sure how many infected beneficiaries will ultimately receive the new treatment, but if for example, 50% of infected Medicare Part D beneficiaries were eventually treated with the $84,000 course of treatment, approximately $11 billion of new spending would enter the Part D system."

The report noted that hepatitis C is more prevalent among low-income individuals, placing an additional cost burden on the government, as these people are either covered by Medicaid or dually eligible for Medicare and Medicaid.

Milliman based its findings on the cost of taking sofosbuvir for 12 weeks, but noted that the "relative use pattern for these drugs is not well established." The analysis does not reflect any potential cost savings from reductions in other medical costs (such as treating chronic liver disease), which may result from using one of these new drugs.

gtwachtman@frontlinemedcom.com

New treatments for hepatitis C could boost federal spending for the Medicare Part D program by up to $5.8 billion in 2015 and lead to a 4.3%-8.6% premium increase for beneficiaries, according to a report by the actuarial firm Milliman, prepared for the Pharmaceutical Care Management Association.

Milliman examined the cost impact of sofosbuvir, marketed by Gilead Sciences as Sovaldi; the drug was approved by the Food and Drug Administration in December 2013 and carries an $84,000 price tag for a 12-week treatment regimen.

"Unlike some other high-cost specialty drugs, the new HCV [hepatitis C virus] drugs have a significant patient base, so their financial impact causes a meaningful and measurable increase in costs to beneficiaries and United States taxpayers," the report said. "No one knows for sure how many infected beneficiaries will ultimately receive the new treatment, but if for example, 50% of infected Medicare Part D beneficiaries were eventually treated with the $84,000 course of treatment, approximately $11 billion of new spending would enter the Part D system."

The report noted that hepatitis C is more prevalent among low-income individuals, placing an additional cost burden on the government, as these people are either covered by Medicaid or dually eligible for Medicare and Medicaid.

Milliman based its findings on the cost of taking sofosbuvir for 12 weeks, but noted that the "relative use pattern for these drugs is not well established." The analysis does not reflect any potential cost savings from reductions in other medical costs (such as treating chronic liver disease), which may result from using one of these new drugs.

gtwachtman@frontlinemedcom.com

MELBOURNE – A regimen of ABT-450 coformulated with ritonavir, ombitasvir, and dasabuvir, plus ribavirin, resulted in high rates of sustained virologic response in hepatitis C patients co-infected with HIV. Further, the treatment approach did not have a negative effect on HIV viral load.

Data from the open-label study, presented at the 20th International AIDS Conference, showed that nearly 94% of patients treated with the three-dose (3D) interferon-free regimen plus ribavirin for 12 weeks had a sustained virologic response at 4 weeks after treatment cessation. Nearly 97% of those treated for 24 weeks achieved a sustained virologic response at 4 weeks after treatment cessation.

Biance Nogrady/Frontline Medical News

The TURQUOISE-I study assessed the 3D plus ribavirin regimen in 63 patients with hepatitis C genotype 1 infection plus HIV-1 infection. The treatment group included treatment-naive patients and patients previously treated with interferon.

Dr. Mark S. Sulkowski, who presented the data, said earlier phase III studies of the 3D regimen, both with and without ribavirin, showed greater than 96% sustained virologic response rates in HCV-1–infected patients treated for 12 weeks, and 92%-96% response rates in patients with cirrhosis treated for 12-24 weeks.

"Drug interactions with hepatitis C and HIV regimens are the foremost question when approaching treatment in this group," Dr. Sulkowski, professor of medicine at Johns Hopkins University, Baltimore, told conference attendees.

Virologic failure occurred in two patients. Both had previously not responded to treatment and had compensated cirrhosis, and both also had resistance-associated HCV variants that had not been present at baseline.

The majority of adverse events were mild. The most common was fatigue, affecting 58% of patients in the 12-week arm and 37% in the 24-week arm. Other adverse events included insomnia, nausea, and headache. No patients discontinued therapy because of adverse events.

Researchers also observed grade 3 elevations in total bilirubin levels in more than 35% of patients in the 12-week arm of the study and nearly 19% of patients in the 24-week arm. Most of the grade 3 elevations occurred in patients receiving the antiretroviral atazanavir for their HIV infections.

Dr. Sulkowski said side effects and drug interactions associated with interferon therapy have largely accounted for problems in treating patients co-infected with HIV and hepatitis C.

The emerging data suggest the interferon-free regimen "works just as well in HIV-positive patients as in HIV-negative patients, so the barriers really come down to potential interactions with antiretroviral drugs," Dr. Sulkowski said in an interview.

"We now believe that HIV in and of itself is not a factor in predicting success with interferon-free regimens," he said.

Dr. Sulkowski said the Food and Drug Administration is considering applications for the 3D regimen, with and without ribavirin, with a decision expected in the fall.

Dr. Sulkowski declared grant support, consultancies, and advisory board positions with several companies, including study sponsor AbbVie.

MELBOURNE – A regimen of ABT-450 coformulated with ritonavir, ombitasvir, and dasabuvir, plus ribavirin, resulted in high rates of sustained virologic response in hepatitis C patients co-infected with HIV. Further, the treatment approach did not have a negative effect on HIV viral load.

Data from the open-label study, presented at the 20th International AIDS Conference, showed that nearly 94% of patients treated with the three-dose (3D) interferon-free regimen plus ribavirin for 12 weeks had a sustained virologic response at 4 weeks after treatment cessation. Nearly 97% of those treated for 24 weeks achieved a sustained virologic response at 4 weeks after treatment cessation.

Biance Nogrady/Frontline Medical News

The TURQUOISE-I study assessed the 3D plus ribavirin regimen in 63 patients with hepatitis C genotype 1 infection plus HIV-1 infection. The treatment group included treatment-naive patients and patients previously treated with interferon.

Dr. Mark S. Sulkowski, who presented the data, said earlier phase III studies of the 3D regimen, both with and without ribavirin, showed greater than 96% sustained virologic response rates in HCV-1–infected patients treated for 12 weeks, and 92%-96% response rates in patients with cirrhosis treated for 12-24 weeks.

"Drug interactions with hepatitis C and HIV regimens are the foremost question when approaching treatment in this group," Dr. Sulkowski, professor of medicine at Johns Hopkins University, Baltimore, told conference attendees.

Virologic failure occurred in two patients. Both had previously not responded to treatment and had compensated cirrhosis, and both also had resistance-associated HCV variants that had not been present at baseline.

The majority of adverse events were mild. The most common was fatigue, affecting 58% of patients in the 12-week arm and 37% in the 24-week arm. Other adverse events included insomnia, nausea, and headache. No patients discontinued therapy because of adverse events.

Researchers also observed grade 3 elevations in total bilirubin levels in more than 35% of patients in the 12-week arm of the study and nearly 19% of patients in the 24-week arm. Most of the grade 3 elevations occurred in patients receiving the antiretroviral atazanavir for their HIV infections.

Dr. Sulkowski said side effects and drug interactions associated with interferon therapy have largely accounted for problems in treating patients co-infected with HIV and hepatitis C.

The emerging data suggest the interferon-free regimen "works just as well in HIV-positive patients as in HIV-negative patients, so the barriers really come down to potential interactions with antiretroviral drugs," Dr. Sulkowski said in an interview.

"We now believe that HIV in and of itself is not a factor in predicting success with interferon-free regimens," he said.

Dr. Sulkowski said the Food and Drug Administration is considering applications for the 3D regimen, with and without ribavirin, with a decision expected in the fall.

Dr. Sulkowski declared grant support, consultancies, and advisory board positions with several companies, including study sponsor AbbVie.

MELBOURNE – A regimen of ABT-450 coformulated with ritonavir, ombitasvir, and dasabuvir, plus ribavirin, resulted in high rates of sustained virologic response in hepatitis C patients co-infected with HIV. Further, the treatment approach did not have a negative effect on HIV viral load.

Data from the open-label study, presented at the 20th International AIDS Conference, showed that nearly 94% of patients treated with the three-dose (3D) interferon-free regimen plus ribavirin for 12 weeks had a sustained virologic response at 4 weeks after treatment cessation. Nearly 97% of those treated for 24 weeks achieved a sustained virologic response at 4 weeks after treatment cessation.

Biance Nogrady/Frontline Medical News

The TURQUOISE-I study assessed the 3D plus ribavirin regimen in 63 patients with hepatitis C genotype 1 infection plus HIV-1 infection. The treatment group included treatment-naive patients and patients previously treated with interferon.

Dr. Mark S. Sulkowski, who presented the data, said earlier phase III studies of the 3D regimen, both with and without ribavirin, showed greater than 96% sustained virologic response rates in HCV-1–infected patients treated for 12 weeks, and 92%-96% response rates in patients with cirrhosis treated for 12-24 weeks.

"Drug interactions with hepatitis C and HIV regimens are the foremost question when approaching treatment in this group," Dr. Sulkowski, professor of medicine at Johns Hopkins University, Baltimore, told conference attendees.

Virologic failure occurred in two patients. Both had previously not responded to treatment and had compensated cirrhosis, and both also had resistance-associated HCV variants that had not been present at baseline.

The majority of adverse events were mild. The most common was fatigue, affecting 58% of patients in the 12-week arm and 37% in the 24-week arm. Other adverse events included insomnia, nausea, and headache. No patients discontinued therapy because of adverse events.

Researchers also observed grade 3 elevations in total bilirubin levels in more than 35% of patients in the 12-week arm of the study and nearly 19% of patients in the 24-week arm. Most of the grade 3 elevations occurred in patients receiving the antiretroviral atazanavir for their HIV infections.

Dr. Sulkowski said side effects and drug interactions associated with interferon therapy have largely accounted for problems in treating patients co-infected with HIV and hepatitis C.

The emerging data suggest the interferon-free regimen "works just as well in HIV-positive patients as in HIV-negative patients, so the barriers really come down to potential interactions with antiretroviral drugs," Dr. Sulkowski said in an interview.

"We now believe that HIV in and of itself is not a factor in predicting success with interferon-free regimens," he said.

Dr. Sulkowski said the Food and Drug Administration is considering applications for the 3D regimen, with and without ribavirin, with a decision expected in the fall.

Dr. Sulkowski declared grant support, consultancies, and advisory board positions with several companies, including study sponsor AbbVie.

Veterans with genotype 3 hepatitis C virus infection were 31% more likely to develop cirrhosis and 80% more likely to develop liver cancer than were patients with genotype 1 infection, reported the authors of a large observational retrospective study published in the July issue of Hepatology.

"Our findings have implications that involve the entire spectrum of care, from antiviral treatment to prevention and screening in patients with HCV genotype 3 infection," said Dr. Fasiha Kanwal, of the Michael E. DeBakey Veterans Affairs Medical Center in Houston, and her associates. "Given the accelerated progression to advanced liver disease, patients with HCV genotype 3 may serve as a high-risk group that will need to be prioritized in the era of new antiviral treatments."

But all-oral combination therapy with sofosbuvir and ribavirin may not achieve the high levels of sustained virologic response (SVR) found for patients with genotype 2 infection, Dr. Kanwal and her associates noted. And even if highly effective treatments for genotype 3 infection eventually become available, approximately one-quarter of affected patients would have progressed to cirrhosis and therefore would already be at increased risk for hepatocellular carcinoma, the researchers added.

The study included 110,484 patients with HCV infection from the VA HCV Clinical Case Registry. About 70% of patients were Vietnam-era veterans, the investigators said. Patients were followed for an average of 5.4 years between 2000 and 2009, and a total of 8,337, or 7.5%, had genotype 3 infection, the researchers reported (Hepatology 2014;60:98-105).

After adjustment for factors such as age and year of birth, diabetes, body mass index, and antiviral treatment, patients with genotype 3 infection had the highest risk of developing cirrhosis and hepatocellular carcinoma among all HCV genotypes. Compared with genotype 1–infected patients, genotype 3–infected patients had a 31% higher risk for cirrhosis (adjusted hazard ratio, 1.31; 95% confidence interval, 1.22-1.39) and an 80% higher risk for hepatocellular carcinoma (aHR, 1.81; 95% CI, 1.61-2.03), the investigators added. Furthermore, a subgroup analysis of patients with cirrhosis showed that the risk of hepatocellular carcinoma was 44% higher in patients with genotype 3 infection than in patients with genotype 1 infection, the researchers said.

"These data are relevant to the thousands of HCV patients with genotype 3 infection, and to their physicians who provide care and counseling to this population," said Dr. Kanwal and her associates. They added that the data might help in prioritizing who should first receive future generations of direct-acting antivirals.

The Houston VA Health Services Research and Development Center of Excellence helped fund the study. The authors did not report conflicts of interest.

Veterans with genotype 3 hepatitis C virus infection were 31% more likely to develop cirrhosis and 80% more likely to develop liver cancer than were patients with genotype 1 infection, reported the authors of a large observational retrospective study published in the July issue of Hepatology.

"Our findings have implications that involve the entire spectrum of care, from antiviral treatment to prevention and screening in patients with HCV genotype 3 infection," said Dr. Fasiha Kanwal, of the Michael E. DeBakey Veterans Affairs Medical Center in Houston, and her associates. "Given the accelerated progression to advanced liver disease, patients with HCV genotype 3 may serve as a high-risk group that will need to be prioritized in the era of new antiviral treatments."

But all-oral combination therapy with sofosbuvir and ribavirin may not achieve the high levels of sustained virologic response (SVR) found for patients with genotype 2 infection, Dr. Kanwal and her associates noted. And even if highly effective treatments for genotype 3 infection eventually become available, approximately one-quarter of affected patients would have progressed to cirrhosis and therefore would already be at increased risk for hepatocellular carcinoma, the researchers added.

The study included 110,484 patients with HCV infection from the VA HCV Clinical Case Registry. About 70% of patients were Vietnam-era veterans, the investigators said. Patients were followed for an average of 5.4 years between 2000 and 2009, and a total of 8,337, or 7.5%, had genotype 3 infection, the researchers reported (Hepatology 2014;60:98-105).

After adjustment for factors such as age and year of birth, diabetes, body mass index, and antiviral treatment, patients with genotype 3 infection had the highest risk of developing cirrhosis and hepatocellular carcinoma among all HCV genotypes. Compared with genotype 1–infected patients, genotype 3–infected patients had a 31% higher risk for cirrhosis (adjusted hazard ratio, 1.31; 95% confidence interval, 1.22-1.39) and an 80% higher risk for hepatocellular carcinoma (aHR, 1.81; 95% CI, 1.61-2.03), the investigators added. Furthermore, a subgroup analysis of patients with cirrhosis showed that the risk of hepatocellular carcinoma was 44% higher in patients with genotype 3 infection than in patients with genotype 1 infection, the researchers said.

"These data are relevant to the thousands of HCV patients with genotype 3 infection, and to their physicians who provide care and counseling to this population," said Dr. Kanwal and her associates. They added that the data might help in prioritizing who should first receive future generations of direct-acting antivirals.

The Houston VA Health Services Research and Development Center of Excellence helped fund the study. The authors did not report conflicts of interest.

Veterans with genotype 3 hepatitis C virus infection were 31% more likely to develop cirrhosis and 80% more likely to develop liver cancer than were patients with genotype 1 infection, reported the authors of a large observational retrospective study published in the July issue of Hepatology.

"Our findings have implications that involve the entire spectrum of care, from antiviral treatment to prevention and screening in patients with HCV genotype 3 infection," said Dr. Fasiha Kanwal, of the Michael E. DeBakey Veterans Affairs Medical Center in Houston, and her associates. "Given the accelerated progression to advanced liver disease, patients with HCV genotype 3 may serve as a high-risk group that will need to be prioritized in the era of new antiviral treatments."

But all-oral combination therapy with sofosbuvir and ribavirin may not achieve the high levels of sustained virologic response (SVR) found for patients with genotype 2 infection, Dr. Kanwal and her associates noted. And even if highly effective treatments for genotype 3 infection eventually become available, approximately one-quarter of affected patients would have progressed to cirrhosis and therefore would already be at increased risk for hepatocellular carcinoma, the researchers added.

The study included 110,484 patients with HCV infection from the VA HCV Clinical Case Registry. About 70% of patients were Vietnam-era veterans, the investigators said. Patients were followed for an average of 5.4 years between 2000 and 2009, and a total of 8,337, or 7.5%, had genotype 3 infection, the researchers reported (Hepatology 2014;60:98-105).

After adjustment for factors such as age and year of birth, diabetes, body mass index, and antiviral treatment, patients with genotype 3 infection had the highest risk of developing cirrhosis and hepatocellular carcinoma among all HCV genotypes. Compared with genotype 1–infected patients, genotype 3–infected patients had a 31% higher risk for cirrhosis (adjusted hazard ratio, 1.31; 95% confidence interval, 1.22-1.39) and an 80% higher risk for hepatocellular carcinoma (aHR, 1.81; 95% CI, 1.61-2.03), the investigators added. Furthermore, a subgroup analysis of patients with cirrhosis showed that the risk of hepatocellular carcinoma was 44% higher in patients with genotype 3 infection than in patients with genotype 1 infection, the researchers said.

"These data are relevant to the thousands of HCV patients with genotype 3 infection, and to their physicians who provide care and counseling to this population," said Dr. Kanwal and her associates. They added that the data might help in prioritizing who should first receive future generations of direct-acting antivirals.

The Houston VA Health Services Research and Development Center of Excellence helped fund the study. The authors did not report conflicts of interest.

Everolimus failed to improve overall survival among patients with advanced hepatocellular carcinoma in a large international phase III clinical trial, according to a report published online July 1 in JAMA.

Everolimus – which targets the mTOR pathway that is a key regulator of cellular growth, proliferation, angiogenesis, and survival – had shown promise in numerous preclinical, phase I, and phase II studies. So the Everolimus for Liver Cancer Evaluation (EVOLVE-1) trial was designed to compare the drug’s efficacy and safety against that of a matching placebo in patients whose HCC was refractory to, or who were intolerant of, sorafenib, said Dr. Andrew X. Zhu of Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, and his associates.

Sorafenib is the only systemic therapy shown to improve survival in advanced HCC, but its benefits are "transient and modest," and it produces significant adverse events, according to the researchers. In this study, sorafenib was discontinued because of disease progression in 81% of patients and because of intolerance in 19%, they noted.

In EVOLVE-1, 546 patients were enrolled during a 2-year period at 111 medical centers in 17 countries, randomly assigned in a double-blind fashion to receive either 7.5 mg oral everolimus (362 subjects) or placebo (184 subjects) daily, and followed for a median of 2.5 years (range, 14.8-36.6 months). The trial was sponsored by Novartis, maker of everolimus.

HCC was associated with hepatitis B virus in 26.2% of the patients, hepatitis C virus in 25.1%, and alcohol abuse in 20.0%. There were 303 deaths (83.7%) in the active-treatment group and 151 (82.1%) in the placebo group.

At 5 months, the primary endpoint of estimated overall survival was not significantly different between patients taking everolimus (67.0%) and those taking placebo (65.6%); the rates also were not significantly different at 7 months (53.4% and 51.4%, respectively). Median overall survival time was 7.6 months for everolimus and 7.3 months with placebo, also a nonsignificant difference, Dr. Zhu and his associates said (JAMA 2014 July 1 [doi:10.1001/jama.2014.7189]).

These findings were consistent across all but one subgroup of patients. Secondary endpoints, including time to disease progression, rate of complete response (0% in both groups), and time to deterioration in quality of life, also were not significantly different between the two study groups.

Serious adverse events, including adverse events leading to treatment discontinuation, were more common with everolimus than with placebo. These included asthenia, anemia, decreased appetite, resurgence of HBV, ascites, and thrombocytopenia.

Thus, "despite the strong scientific rationale and preclinical data," everolimus failed to improve outcomes in advanced HCC, the investigators said.

However, "given the immunosuppressive and antitumor effects of mTOR inhibitors, the potential benefits of this class of agents in the adjuvant setting are being assessed in a phase-III trial of sirolimus for patients with HCC after liver transplantation," they added.

Everolimus failed to improve overall survival among patients with advanced hepatocellular carcinoma in a large international phase III clinical trial, according to a report published online July 1 in JAMA.

Everolimus – which targets the mTOR pathway that is a key regulator of cellular growth, proliferation, angiogenesis, and survival – had shown promise in numerous preclinical, phase I, and phase II studies. So the Everolimus for Liver Cancer Evaluation (EVOLVE-1) trial was designed to compare the drug’s efficacy and safety against that of a matching placebo in patients whose HCC was refractory to, or who were intolerant of, sorafenib, said Dr. Andrew X. Zhu of Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, and his associates.

Sorafenib is the only systemic therapy shown to improve survival in advanced HCC, but its benefits are "transient and modest," and it produces significant adverse events, according to the researchers. In this study, sorafenib was discontinued because of disease progression in 81% of patients and because of intolerance in 19%, they noted.

In EVOLVE-1, 546 patients were enrolled during a 2-year period at 111 medical centers in 17 countries, randomly assigned in a double-blind fashion to receive either 7.5 mg oral everolimus (362 subjects) or placebo (184 subjects) daily, and followed for a median of 2.5 years (range, 14.8-36.6 months). The trial was sponsored by Novartis, maker of everolimus.

HCC was associated with hepatitis B virus in 26.2% of the patients, hepatitis C virus in 25.1%, and alcohol abuse in 20.0%. There were 303 deaths (83.7%) in the active-treatment group and 151 (82.1%) in the placebo group.

At 5 months, the primary endpoint of estimated overall survival was not significantly different between patients taking everolimus (67.0%) and those taking placebo (65.6%); the rates also were not significantly different at 7 months (53.4% and 51.4%, respectively). Median overall survival time was 7.6 months for everolimus and 7.3 months with placebo, also a nonsignificant difference, Dr. Zhu and his associates said (JAMA 2014 July 1 [doi:10.1001/jama.2014.7189]).

These findings were consistent across all but one subgroup of patients. Secondary endpoints, including time to disease progression, rate of complete response (0% in both groups), and time to deterioration in quality of life, also were not significantly different between the two study groups.

Serious adverse events, including adverse events leading to treatment discontinuation, were more common with everolimus than with placebo. These included asthenia, anemia, decreased appetite, resurgence of HBV, ascites, and thrombocytopenia.

Thus, "despite the strong scientific rationale and preclinical data," everolimus failed to improve outcomes in advanced HCC, the investigators said.

However, "given the immunosuppressive and antitumor effects of mTOR inhibitors, the potential benefits of this class of agents in the adjuvant setting are being assessed in a phase-III trial of sirolimus for patients with HCC after liver transplantation," they added.

Everolimus failed to improve overall survival among patients with advanced hepatocellular carcinoma in a large international phase III clinical trial, according to a report published online July 1 in JAMA.

Everolimus – which targets the mTOR pathway that is a key regulator of cellular growth, proliferation, angiogenesis, and survival – had shown promise in numerous preclinical, phase I, and phase II studies. So the Everolimus for Liver Cancer Evaluation (EVOLVE-1) trial was designed to compare the drug’s efficacy and safety against that of a matching placebo in patients whose HCC was refractory to, or who were intolerant of, sorafenib, said Dr. Andrew X. Zhu of Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, and his associates.

Sorafenib is the only systemic therapy shown to improve survival in advanced HCC, but its benefits are "transient and modest," and it produces significant adverse events, according to the researchers. In this study, sorafenib was discontinued because of disease progression in 81% of patients and because of intolerance in 19%, they noted.

In EVOLVE-1, 546 patients were enrolled during a 2-year period at 111 medical centers in 17 countries, randomly assigned in a double-blind fashion to receive either 7.5 mg oral everolimus (362 subjects) or placebo (184 subjects) daily, and followed for a median of 2.5 years (range, 14.8-36.6 months). The trial was sponsored by Novartis, maker of everolimus.

HCC was associated with hepatitis B virus in 26.2% of the patients, hepatitis C virus in 25.1%, and alcohol abuse in 20.0%. There were 303 deaths (83.7%) in the active-treatment group and 151 (82.1%) in the placebo group.

At 5 months, the primary endpoint of estimated overall survival was not significantly different between patients taking everolimus (67.0%) and those taking placebo (65.6%); the rates also were not significantly different at 7 months (53.4% and 51.4%, respectively). Median overall survival time was 7.6 months for everolimus and 7.3 months with placebo, also a nonsignificant difference, Dr. Zhu and his associates said (JAMA 2014 July 1 [doi:10.1001/jama.2014.7189]).

These findings were consistent across all but one subgroup of patients. Secondary endpoints, including time to disease progression, rate of complete response (0% in both groups), and time to deterioration in quality of life, also were not significantly different between the two study groups.

Serious adverse events, including adverse events leading to treatment discontinuation, were more common with everolimus than with placebo. These included asthenia, anemia, decreased appetite, resurgence of HBV, ascites, and thrombocytopenia.

Thus, "despite the strong scientific rationale and preclinical data," everolimus failed to improve outcomes in advanced HCC, the investigators said.

However, "given the immunosuppressive and antitumor effects of mTOR inhibitors, the potential benefits of this class of agents in the adjuvant setting are being assessed in a phase-III trial of sirolimus for patients with HCC after liver transplantation," they added.

Medicare will cover screening for hepatitis C virus infection in high-risk beneficiaries, including a one-time screening for all beneficiaries born between 1946 and 1964, according to a national coverage decision announced June 2.

High risk is defined in the coverage memo as persons who have "a current or past history of illicit injection drug use; and persons who have a history of receiving a blood transfusion prior to 1992." To be covered, screening must be ordered by the beneficiary’s primary care physician or another practitioner within the primary care setting.

©Pearl Jackson/iStockphoto.com

Annual rescreening is also covered for high-risk beneficiaries who continue to use illicit injection drugs, according to the decision memo.

The Centers for Medicare & Medicaid Services proposed the coverage, which follows U.S. Preventive Services Task Force recommendations for screening in March. That proposal followed an overwhelmingly positive response to the agency’s initial consideration of coverage for HCV screening in September 2013.

Treatment options for hepatitis C are expanding, with FDA approving three protease inhibitors in recent years – boceprevir (Victrelis), telaprevir (Incivek), and simeprevir (Olysio) – for treatment of patients with genotype 1 infection. Each of these treatments can be used in combination with pegylated interferon and ribavirin for the treatment of genotype 1 infection.

Last year, FDA approved sofosbuvir (Sovaldi), indicated for infections from genotypes 1, 2, 3, or 4, although access is hindered by its cost: $84,000 for a 12-week course of treatment ($1,000 a pill).

gtwachtman@frontlinemedcom.com

Medicare will cover screening for hepatitis C virus infection in high-risk beneficiaries, including a one-time screening for all beneficiaries born between 1946 and 1964, according to a national coverage decision announced June 2.

High risk is defined in the coverage memo as persons who have "a current or past history of illicit injection drug use; and persons who have a history of receiving a blood transfusion prior to 1992." To be covered, screening must be ordered by the beneficiary’s primary care physician or another practitioner within the primary care setting.

©Pearl Jackson/iStockphoto.com

Annual rescreening is also covered for high-risk beneficiaries who continue to use illicit injection drugs, according to the decision memo.

The Centers for Medicare & Medicaid Services proposed the coverage, which follows U.S. Preventive Services Task Force recommendations for screening in March. That proposal followed an overwhelmingly positive response to the agency’s initial consideration of coverage for HCV screening in September 2013.

Treatment options for hepatitis C are expanding, with FDA approving three protease inhibitors in recent years – boceprevir (Victrelis), telaprevir (Incivek), and simeprevir (Olysio) – for treatment of patients with genotype 1 infection. Each of these treatments can be used in combination with pegylated interferon and ribavirin for the treatment of genotype 1 infection.

Last year, FDA approved sofosbuvir (Sovaldi), indicated for infections from genotypes 1, 2, 3, or 4, although access is hindered by its cost: $84,000 for a 12-week course of treatment ($1,000 a pill).

gtwachtman@frontlinemedcom.com

Medicare will cover screening for hepatitis C virus infection in high-risk beneficiaries, including a one-time screening for all beneficiaries born between 1946 and 1964, according to a national coverage decision announced June 2.

High risk is defined in the coverage memo as persons who have "a current or past history of illicit injection drug use; and persons who have a history of receiving a blood transfusion prior to 1992." To be covered, screening must be ordered by the beneficiary’s primary care physician or another practitioner within the primary care setting.

©Pearl Jackson/iStockphoto.com

Annual rescreening is also covered for high-risk beneficiaries who continue to use illicit injection drugs, according to the decision memo.

The Centers for Medicare & Medicaid Services proposed the coverage, which follows U.S. Preventive Services Task Force recommendations for screening in March. That proposal followed an overwhelmingly positive response to the agency’s initial consideration of coverage for HCV screening in September 2013.

Treatment options for hepatitis C are expanding, with FDA approving three protease inhibitors in recent years – boceprevir (Victrelis), telaprevir (Incivek), and simeprevir (Olysio) – for treatment of patients with genotype 1 infection. Each of these treatments can be used in combination with pegylated interferon and ribavirin for the treatment of genotype 1 infection.

Last year, FDA approved sofosbuvir (Sovaldi), indicated for infections from genotypes 1, 2, 3, or 4, although access is hindered by its cost: $84,000 for a 12-week course of treatment ($1,000 a pill).

gtwachtman@frontlinemedcom.com