EDITORIAL
New England Journal Of Medicine
Simple, Effective, but Out of Reach? Public Health Implications of HCV Drugs
John W. Ward, M.D., and Jonathan H. Mermin, M.D., M.P.H.Simple, Effective, but Out of Reach? Public Health Implications of HCV Drugs
November 17, 2015
DOI: 10.1056/NEJMe1513245
The results of four clinical trials showing the excellent safety and efficacy of a 12-week course of sofosbuvir (an NS5B inhibitor licensed in the United States in 2013) and velpatasvir (a new NS5A inhibitor) in treating patients with hepatitis C infection (HCV) are reported now in the Journal.1-3 In two of these studies, ASTRAL-1 and ASTRAL-2, 97 to 100% of patients with HCV genotype 1a, 1b, 2, 4, 5, or 6 had a sustained virologic response at 12 weeks after the end of therapy, a marker that is indicative of virologic cure. Similar efficacy was observed among patients in whom previous treatment had failed and those with compensated cirrhosis, factors that have been associated with a reduced response to the treatment of HCV infection.4
We conducted a phase 3 trial (ASTRAL-1) to assess the efficacy and safety of 12 weeks of treatment with a fixed-dose combination of velpatasvir and sofosbuvir among both previously treated and untreated patients who were chronically infected with HCV genotype 1, 2, 4, 5, or 6, including those with compensated cirrhosis.
Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection
Here, we present the results of two randomized, controlled, phase 3 trials (ASTRAL-2 and ASTRAL-3) in which treatment with a fixed-dose combination tablet of sofosbuvir and velpatasvir for 12 weeks was compared with standard treatment with sofosbuvir plus ribavirin for 12 or 24 weeks in patients who had received prior treatment for HCV genotype 2 or 3 infection and in those who had not received such treatment, including those with compensated cirrhosis.Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection
Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis
LB-2 A Phase 3 Double-Blind Placebo-Controlled Evaluation of Sofosbuvir/Velpatasvir Fixed Dose Combination for 12 Weeks in Naïve and Experienced Genotype 1, 2, 4, 5, 6 HCV Infected Patients with and without cirrhosis: Results of the ASTRAL-1 Study
Simple drug regimen cures hepatitis C virus in patients after 12 weeks
Chronic HCV is known as a "silent" killer because symptoms often don't appear until the liver is severely damaged. Left undiagnosed, HCV can lead to cirrhosis which can progress to liver failure or liver cancer. HCV is primarily spread by blood-to-blood contact and is associated with intravenous drug use, contact with poorly sterilized medical equipment and blood transfusions before 1992.
Researchers at the Toronto Western Hospital (TWH) Liver Clinic have found that a simple drug regimen delivered over 12 weeks achieved sustained eradication of several genotypes of the hepatitis C virus (HCV) in 99 per cent of the trial's patients.
The study, released in the New England Journal of Medicine, showed that receiving a once daily drug combination of sofosbuvir-velpatasvir for a 12 week period was effective in both treatment-naïve and previously treated patients with HCV genotype 1, 2, 4, 5, or 6, including those with compensated cirrhosis (where scarring of the liver has occurred but patients have yet to experience symptoms as a result of it).
"This drug regimen changes the standard of care in treating patients with HCV -- we can now cure almost everyone with a very simple treatment," said Dr. Jordan Feld, Hepatologist, Francis Family Liver Clinic, TWH and the first author of the study. "It's incredibly gratifying to be part of research where we not only cure a disease but can also think about eliminating HCV in Canada."
Current approved treatments for chronic HCV are not equally effective in combating the virus' different genotypes. Testing to determine the genotype and subtype of the virus is required before treatment could be initiated. But the combination of sofosbuvir-velpatasvir has been shown to be applicable to all strains of HCV, effectively eliminating the need to test for the viral genotype -- an obstacle that often delayed treatment.
The regimen was tested in an international, randomized, double-blind placebo-controlled phase three trial conducted at 81 sites in eight different countries. After 12 weeks, 99 per cent of the 624 patients who had been treated with a daily tablet of sofosbuvir-velpatasvir experienced a sustained virologic response -- the medical term for eradication or cure of HCV -- meaning that patients remained free of the virus three months after completing treatment. None of the 116 patients receiving a placebo experienced the same result.
"This is truly a one size fits all treatment that is very easy to administer and extremely well tolerated," said Dr. Feld. "Our challenge now is getting treatment to those who need it. Over half of people living with hepatitis C remain undiagnosed. Fortunately this regimen, along with other advances in therapy, will allow us to move treatment out of specialty clinics so that we can deliver care and ideally cure all infected Canadians."
Chronic HCV is known as a "silent" killer because symptoms often don't appear until the liver is severely damaged. Left undiagnosed, HCV can lead to cirrhosis which can progress to liver failure or liver cancer. HCV is primarily spread by blood-to-blood contact and is associated with intravenous drug use, contact with poorly sterilized medical equipment and blood transfusions before 1992.
Approximately 170 million people are infected with chronic HCV worldwide with an estimated 252,000 in Canada. HCV causes the greatest burden of disease, measured in years of life lost, than any infectious disease in Canada.
Story Source:
The above post is reprinted from materials provided by University Health Network (UHN). Note: Materials may be edited for content and length.
Journal Reference:
Jordan J. Feld, Ira M. Jacobson, Christophe Hézode, Tarik Asselah, Peter J. Ruane, Norbert Gruener, Armand Abergel, Alessandra Mangia, Ching-Lung Lai, Henry L.Y. Chan, Francesco Mazzotta, Christophe Moreno, Eric Yoshida, Stephen D. Shafran, William J. Towner, Tram T. Tran, John McNally, Anu Osinusi, Evguenia Svarovskaia, Yanni Zhu, Diana M. Brainard, John G. McHutchison, Kosh Agarwal, Stefan Zeuzem.Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. New England Journal of Medicine, 2015; 151116141724000
The number of patients with decompensated cirrhosis caused by chronic infection with the hepatitis C virus (HCV) is projected to rise in the coming decade.1 For many years, the only treatment option for such patients was liver transplantation. Recently, however, clinical trials of newly approved direct-acting antiviral agents have shown that it is possible to treat HCV infection safely and effectively in patients with decompensated cirrhosis and that successful treatment is associated with early improvement in liver function.2-11 The possible long-term benefits of treatment on existing liver disease remain unknown. The only regimen that is currently approved for the treatment of HCV infection in patients with decompensated cirrhosis is 24 weeks of ledipasvir–sofosbuvir plus ribavirin, which is approved in Europe for patients with HCV genotypes 1 and 4.12 A highly effective regimen to treat HCV infection of all genotypes in patients with decompensated liver disease that has acceptable side effects would address a significant unmet medical need.
The NS5B nucleotide inhibitor sofosbuvir is approved for the treatment of HCV infection in combination with other agents.13,14 Velpatasvir (formerly known as GS-5816, Gilead Sciences) is an investigational inhibitor of the HCV NS5A protein with antiviral activity against all HCV genotypes.15-17 The combination of velpatasvir and sofosbuvir with or without ribavirin provided high rates of sustained virologic response in patients with all HCV genotypes in phase 2 clinical trials.18,19 In the phase 3 ASTRAL-1, ASTRAL-2, and ASTRAL-3 trials (now published in theJournal),20,21 treatment with sofosbuvir–velpatasvir in a fixed-dose combination tablet for 12 weeks resulted in high rates of sustained virologic response among patients with HCV genotypes 1 through 6 without cirrhosis or with compensated cirrhosis.
We conducted a phase 3, open-label trial to assess the efficacy and safety of a fixed dose of sofosbuvir–velpatasvir with or without ribavirin for 12 weeks or sofosbuvir–velpatasvir for 24 weeks in patients infected with HCV genotypes 1 through 6 and with decompensated cirrhosis...
The NS5B nucleotide inhibitor sofosbuvir is approved for the treatment of HCV infection in combination with other agents.13,14 Velpatasvir (formerly known as GS-5816, Gilead Sciences) is an investigational inhibitor of the HCV NS5A protein with antiviral activity against all HCV genotypes.15-17 The combination of velpatasvir and sofosbuvir with or without ribavirin provided high rates of sustained virologic response in patients with all HCV genotypes in phase 2 clinical trials.18,19 In the phase 3 ASTRAL-1, ASTRAL-2, and ASTRAL-3 trials (now published in theJournal),20,21 treatment with sofosbuvir–velpatasvir in a fixed-dose combination tablet for 12 weeks resulted in high rates of sustained virologic response among patients with HCV genotypes 1 through 6 without cirrhosis or with compensated cirrhosis.
We conducted a phase 3, open-label trial to assess the efficacy and safety of a fixed dose of sofosbuvir–velpatasvir with or without ribavirin for 12 weeks or sofosbuvir–velpatasvir for 24 weeks in patients infected with HCV genotypes 1 through 6 and with decompensated cirrhosis...
AASLD Coverage @ Healio
ASTRAL-1: Sofosbuvir/velpatasvir shows pangenotypic activity
SAN FRANCISCO — A fixed-dose combination of Sovaldi and velpatasvir yielded 99% SVR12 across a number of genotypes, according to a presentation at the Late Breakers session of The Liver Meeting 2015.
“Although there has been phenomenal progress in HCV therapy over the last few years, interferon-free regimens are not pangenotypic and, therefore, most regimens need to be selected for specific patient groups,” Jordan J. Feld, MD, of the Toronto Western Hospital Liver Centre, said in his presentation.
ASTRAL-1: Sofosbuvir/velpatasvir shows pangenotypic activity
SAN FRANCISCO — A fixed-dose combination of Sovaldi and velpatasvir yielded 99% SVR12 across a number of genotypes, according to a presentation at the Late Breakers session of The Liver Meeting 2015.
“Although there has been phenomenal progress in HCV therapy over the last few years, interferon-free regimens are not pangenotypic and, therefore, most regimens need to be selected for specific patient groups,” Jordan J. Feld, MD, of the Toronto Western Hospital Liver Centre, said in his presentation.
AASLD Late-Breaking Abstract Session
Monday, November 16, 2:45 pm - 4:30 pmLB-2 A Phase 3 Double-Blind Placebo-Controlled Evaluation of Sofosbuvir/Velpatasvir Fixed Dose Combination for 12 Weeks in Naïve and Experienced Genotype 1, 2, 4, 5, 6 HCV Infected Patients with and without cirrhosis: Results of the ASTRAL-1 Study
Simple drug regimen cures hepatitis C virus in patients after 12 weeks
November 16, 2015
Source:University Health Network (UHN)
Summary:Researchers have found that a simple drug regimen delivered over 12 weeks achieved sustained eradication of several genotypes of the hepatitis C virus (HCV) in 99 per cent of the trial's patients.
Chronic HCV is known as a "silent" killer because symptoms often don't appear until the liver is severely damaged. Left undiagnosed, HCV can lead to cirrhosis which can progress to liver failure or liver cancer. HCV is primarily spread by blood-to-blood contact and is associated with intravenous drug use, contact with poorly sterilized medical equipment and blood transfusions before 1992.
Researchers at the Toronto Western Hospital (TWH) Liver Clinic have found that a simple drug regimen delivered over 12 weeks achieved sustained eradication of several genotypes of the hepatitis C virus (HCV) in 99 per cent of the trial's patients.
The study, released in the New England Journal of Medicine, showed that receiving a once daily drug combination of sofosbuvir-velpatasvir for a 12 week period was effective in both treatment-naïve and previously treated patients with HCV genotype 1, 2, 4, 5, or 6, including those with compensated cirrhosis (where scarring of the liver has occurred but patients have yet to experience symptoms as a result of it).
"This drug regimen changes the standard of care in treating patients with HCV -- we can now cure almost everyone with a very simple treatment," said Dr. Jordan Feld, Hepatologist, Francis Family Liver Clinic, TWH and the first author of the study. "It's incredibly gratifying to be part of research where we not only cure a disease but can also think about eliminating HCV in Canada."
Current approved treatments for chronic HCV are not equally effective in combating the virus' different genotypes. Testing to determine the genotype and subtype of the virus is required before treatment could be initiated. But the combination of sofosbuvir-velpatasvir has been shown to be applicable to all strains of HCV, effectively eliminating the need to test for the viral genotype -- an obstacle that often delayed treatment.
The regimen was tested in an international, randomized, double-blind placebo-controlled phase three trial conducted at 81 sites in eight different countries. After 12 weeks, 99 per cent of the 624 patients who had been treated with a daily tablet of sofosbuvir-velpatasvir experienced a sustained virologic response -- the medical term for eradication or cure of HCV -- meaning that patients remained free of the virus three months after completing treatment. None of the 116 patients receiving a placebo experienced the same result.
"This is truly a one size fits all treatment that is very easy to administer and extremely well tolerated," said Dr. Feld. "Our challenge now is getting treatment to those who need it. Over half of people living with hepatitis C remain undiagnosed. Fortunately this regimen, along with other advances in therapy, will allow us to move treatment out of specialty clinics so that we can deliver care and ideally cure all infected Canadians."
Chronic HCV is known as a "silent" killer because symptoms often don't appear until the liver is severely damaged. Left undiagnosed, HCV can lead to cirrhosis which can progress to liver failure or liver cancer. HCV is primarily spread by blood-to-blood contact and is associated with intravenous drug use, contact with poorly sterilized medical equipment and blood transfusions before 1992.
Approximately 170 million people are infected with chronic HCV worldwide with an estimated 252,000 in Canada. HCV causes the greatest burden of disease, measured in years of life lost, than any infectious disease in Canada.
Story Source:
The above post is reprinted from materials provided by University Health Network (UHN). Note: Materials may be edited for content and length.
Journal Reference:
Jordan J. Feld, Ira M. Jacobson, Christophe Hézode, Tarik Asselah, Peter J. Ruane, Norbert Gruener, Armand Abergel, Alessandra Mangia, Ching-Lung Lai, Henry L.Y. Chan, Francesco Mazzotta, Christophe Moreno, Eric Yoshida, Stephen D. Shafran, William J. Towner, Tram T. Tran, John McNally, Anu Osinusi, Evguenia Svarovskaia, Yanni Zhu, Diana M. Brainard, John G. McHutchison, Kosh Agarwal, Stefan Zeuzem.Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. New England Journal of Medicine, 2015; 151116141724000
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