All adolescent patients available for follow-up after treatment with Harvoni for chronic hepatitis C genotype 1 achieved sustained virologic response at 12 weeks with no serious adverse events, further supporting its approval in this population.
“Treatment of pediatric patients has been controversial as the current standard of care, pegylated interferon and weight-based ribavirin, is associated with significant side effects, including growth impairment, and poor tolerability,” William F. Balistreri, MD, from the Cincinnati Children’s Hospital Medical Center, and colleagues wrote. “Similar to what has been observed in adults, treatment with ledipasvir-sofosbuvir was well tolerated in adolescents.”
From November 2014 to October 2015, researchers evaluated the safety and efficacy of Harvoni (ledipasvir/sofosbuvir, Gilead Sciences) in 100 patients aged 12 years to 17 years with chronic HCV genotype 1a (81%) or 1b (19%) in a phase 2 trial. Most patients were treatment-naive (80%), white (90%) and female (63%).
Ninety-eight patients achieved SVR at week 12 (95% CI, 93-100). Two patients were lost to follow-up. The rate of SVR was 98% (95% CI, 91-100) among treatment-naive patients. All patients who were treatment-experienced achieved SVR (95% CI, 83-100).
The most common adverse events included headache (27%), diarrhea (14%) and fatigue (13%), all of which were of mild or moderate intensity. The researchers observed no serious adverse events and no patient discontinued due to adverse events.
During a pharmacokinetic analysis, the plasma exposures of sofosbuvir, ledipasvir and GS-331007 in the adolescent patients were within the predefined pharmacokinetic equivalence boundaries of 50% to 200% compared with adults from the phase 2 and 3 studies of Harvoni.
Five patients had NS5A resistance-associated substitutions (RAS) and 5 had NS5B RAS, all of whom were treatment naive and achieved SVR.
“Many children with chronic HCV have deferred treatment until these newer options receive approval for pediatric use, putting them at risk for disease progression,” Balistreri and colleagues concluded. “Successful treatment of children with HCV could have several public health benefits, including reductions in the rates of disease progression and transmission. Data from adults indicate that successful treatment with ledipasvir-sofosbuvir leads to improvements in quality of life.”
My other issue (regarding GT 3 options) goes something like this ... "Now, you just sit there young man until you finish every riba pill on your plate"! Gee Mom, do i have to, couldn't I have something else?
Ahhh my dear C,
Your statement is a good one! Until now, in a world seemingly gone, the only options included the addition of another picnic favorite, Interferon and if you were lucky a new NS3/4 DAA. Children needing treatment had poor or no options then and it's disappointing that they are still waiting.
Now eat your Riba and go lather up the oatmeal bath...
Canuck said
Apr 9, 2017
Yep, like I said ... plenty of "food for thought" here ... no need to titre down "a fixed adult dose" of ledi/sofa (or any new DAA actually) when we can just simply wait to minimize unknown liabilities for a small body/organs/kidneys to reach the correct size/age/weight to fit the dosages and handle excretion! Very convenient as far as supply, not to have to provide yet another formula (ie. reduced dosages) to a child earler (other than what is already readily available on the market (90 ledi/400 sofa), just wait until all the customers are big enough! One size fits all.
My other issue (regarding GT 3 options) goes something like this ... "Now, you just sit there young man until you finish every riba pill on your plate"! Gee Mom, do i have to, couldn't I have something else?
Tig said
Apr 9, 2017
The restrictions are entirely due to dose limitations. They don't have a reduced dose pediatric regimen last I checked. If push came to shove Inbet a compounding Pharmacist could reduce it to a mg/kg dose. Would be totally off label application of it and liability would be high for those attempting it without authorization. That said I'm sure it would be easily accomplished. There shouldn't be a problem waiting until they fit the guidelines though.
The incidence of damage at such a young age is going to be low based solely on time. That is just an opinion of course! I wouldn't put anyone on an Interferon backboned protocol at this time, especially a child. The powers that be wouldn't be too keen to do it either. That stuff is harsh and would be a hard ride for a child.
Canuck said
Apr 9, 2017
I was a little disappointed with this news, not in a treatment plan for kids, nor in use of ledi, but with the age/size caveats - must wait until age 12 and weigh 35kgs (there is a lot of food for thought in that scenario). More so I am troubled and would be conflicted in only being able to offer sofa/riba to my precious little GT3, when I have been cured on the likes of epclusa!
FDA Clears Two HCV Drugs for Children
Megan Brooks April 07, 2017
The US Food and Drug Administration (FDA) has approved the use of sofosbuvir (Sovaldi) and the combination of ledipasvir and sofosbuvir (Harvoni) for hepatitis C virus (HCV) infection in children aged 12 and older and weighing at least 35 kg.
Sofosbuvir and ledipasvir-sofosbuvir from Gilead Sciences are already approved to treat HCV infection in adults. They now become the first direct-acting antiviral treatments approved for children and adolescents with HCV in the United States.
"These approvals will help change the landscape for HCV treatment by addressing an unmet need in children and adolescents," Edward Cox, MD, director of the Office of Antimicrobial Products in the FDA's Center for Drug Evaluation and Research, said in a news release.
The approval of Gilead's supplemental applications for sofosbuvir and ledipasvir-sofosbuvir provide clinicians with pediatric treatment options for six major genotypes of HCV.
Ledipasvir-sofosbuvir is indicated for the treatment of children with HCV genotype 1, 4, 5, or 6 infection without cirrhosis or with mild cirrhosis. Sofosbuvir in combination with ribavirin is indicated for children with genotype 2 or 3 HCV infection without cirrhosis or with mild cirrhosis.
The safety, pharmacokinetics, and efficacy of ledipasvir-sofosbuvir for HCV genotype 1 infection were established in an open-label, multicenter clinical trial that included 100 children aged 12 years and older. The results were on par with those seen in adults, with 98% of patients having no virus detected in the blood 12 weeks after finishing treatment, the FDA says.
The safety and efficacy of ledipasvir-sofosbuvir for HCV genotype 4, 5, or 6 infection in children are based on data showing similar exposures to the drugs in adults and adolescents with HCV genotype 1 infection, as well as similar efficacy and exposures to ledipasvir-sofosbuvir across HCV genotypes 1, 4, 5, and 6 in adults, the agency notes.
Sofosbuvir plus ribavirin was evaluated in an open-label study in 50 children aged 12 years and older. All patients with HCV genotype 2 and 97% of those with HCV genotype 3 had undetectable virus 12 weeks after finishing treatment.
Fatigue and headache were the most common adverse reactions observed with sofosbuvir-ribavirin and ledipasvir-sofosbuvir treatment.
Hepatitis B virus (HBV)reactivation has been reported in HCV/HBV-coinfected adultstreated with direct-acting antivirals for HCV. Current guidelines from the American Association for the Study of Liver Diseases and the Infectious Diseases Society of Americarecommend screening patients for HBV infectionbefore beginning treatment with a direct-acting antiviral medication.
Harvoni safe, effective in teens with HCV genotype 1
Balistreri WF, et al. Hepatol. 2017;doi:10.1002/hep.28995.
August 24, 2017
All adolescent patients available for follow-up after treatment with Harvoni for chronic hepatitis C genotype 1 achieved sustained virologic response at 12 weeks with no serious adverse events, further supporting its approval in this population.
“Treatment of pediatric patients has been controversial as the current standard of care, pegylated interferon and weight-based ribavirin, is associated with significant side effects, including growth impairment, and poor tolerability,” William F. Balistreri, MD, from the Cincinnati Children’s Hospital Medical Center, and colleagues wrote. “Similar to what has been observed in adults, treatment with ledipasvir-sofosbuvir was well tolerated in adolescents.”
From November 2014 to October 2015, researchers evaluated the safety and efficacy of Harvoni (ledipasvir/sofosbuvir, Gilead Sciences) in 100 patients aged 12 years to 17 years with chronic HCV genotype 1a (81%) or 1b (19%) in a phase 2 trial. Most patients were treatment-naive (80%), white (90%) and female (63%).
Ninety-eight patients achieved SVR at week 12 (95% CI, 93-100). Two patients were lost to follow-up. The rate of SVR was 98% (95% CI, 91-100) among treatment-naive patients. All patients who were treatment-experienced achieved SVR (95% CI, 83-100).
The most common adverse events included headache (27%), diarrhea (14%) and fatigue (13%), all of which were of mild or moderate intensity. The researchers observed no serious adverse events and no patient discontinued due to adverse events.
During a pharmacokinetic analysis, the plasma exposures of sofosbuvir, ledipasvir and GS-331007 in the adolescent patients were within the predefined pharmacokinetic equivalence boundaries of 50% to 200% compared with adults from the phase 2 and 3 studies of Harvoni.
Five patients had NS5A resistance-associated substitutions (RAS) and 5 had NS5B RAS, all of whom were treatment naive and achieved SVR.
“Many children with chronic HCV have deferred treatment until these newer options receive approval for pediatric use, putting them at risk for disease progression,” Balistreri and colleagues concluded. “Successful treatment of children with HCV could have several public health benefits, including reductions in the rates of disease progression and transmission. Data from adults indicate that successful treatment with ledipasvir-sofosbuvir leads to improvements in quality of life.”
Credit to: Healio/HCV Next
Ahhh my dear C,
Your statement is a good one! Until now, in a world seemingly gone, the only options included the addition of another picnic favorite, Interferon and if you were lucky a new NS3/4 DAA. Children needing treatment had poor or no options then and it's disappointing that they are still waiting.
Now eat your Riba and go lather up the oatmeal bath...
Yep, like I said ... plenty of "food for thought" here ... no need to titre down "a fixed adult dose" of ledi/sofa (or any new DAA actually) when we can just simply wait to minimize unknown liabilities for a small body/organs/kidneys to reach the correct size/age/weight to fit the dosages and handle excretion! Very convenient as far as supply, not to have to provide yet another formula (ie. reduced dosages) to a child earler (other than what is already readily available on the market (90 ledi/400 sofa), just wait until all the customers are big enough! One size fits all.
My other issue (regarding GT 3 options) goes something like this ... "Now, you just sit there young man until you finish every riba pill on your plate"! Gee Mom, do i have to, couldn't I have something else?
The restrictions are entirely due to dose limitations. They don't have a reduced dose pediatric regimen last I checked. If push came to shove Inbet a compounding Pharmacist could reduce it to a mg/kg dose. Would be totally off label application of it and liability would be high for those attempting it without authorization. That said I'm sure it would be easily accomplished. There shouldn't be a problem waiting until they fit the guidelines though.
The incidence of damage at such a young age is going to be low based solely on time. That is just an opinion of course! I wouldn't put anyone on an Interferon backboned protocol at this time, especially a child. The powers that be wouldn't be too keen to do it either. That stuff is harsh and would be a hard ride for a child.
I was a little disappointed with this news, not in a treatment plan for kids, nor in use of ledi, but with the age/size caveats - must wait until age 12 and weigh 35kgs (there is a lot of food for thought in that scenario). More so I am troubled and would be conflicted in only being able to offer sofa/riba to my precious little GT3, when I have been cured on the likes of epclusa!
FDA Clears Two HCV Drugs for Children
Megan Brooks April 07, 2017
The US Food and Drug Administration (FDA) has approved the use of sofosbuvir (Sovaldi) and the combination of ledipasvir and sofosbuvir (Harvoni) for hepatitis C virus (HCV) infection in children aged 12 and older and weighing at least 35 kg.
Sofosbuvir and ledipasvir-sofosbuvir from Gilead Sciences are already approved to treat HCV infection in adults. They now become the first direct-acting antiviral treatments approved for children and adolescents with HCV in the United States.
"These approvals will help change the landscape for HCV treatment by addressing an unmet need in children and adolescents," Edward Cox, MD, director of the Office of Antimicrobial Products in the FDA's Center for Drug Evaluation and Research, said in a news release.
The approval of Gilead's supplemental applications for sofosbuvir and ledipasvir-sofosbuvir provide clinicians with pediatric treatment options for six major genotypes of HCV.
Ledipasvir-sofosbuvir is indicated for the treatment of children with HCV genotype 1, 4, 5, or 6 infection without cirrhosis or with mild cirrhosis. Sofosbuvir in combination with ribavirin is indicated for children with genotype 2 or 3 HCV infection without cirrhosis or with mild cirrhosis.
The safety, pharmacokinetics, and efficacy of ledipasvir-sofosbuvir for HCV genotype 1 infection were established in an open-label, multicenter clinical trial that included 100 children aged 12 years and older. The results were on par with those seen in adults, with 98% of patients having no virus detected in the blood 12 weeks after finishing treatment, the FDA says.
The safety and efficacy of ledipasvir-sofosbuvir for HCV genotype 4, 5, or 6 infection in children are based on data showing similar exposures to the drugs in adults and adolescents with HCV genotype 1 infection, as well as similar efficacy and exposures to ledipasvir-sofosbuvir across HCV genotypes 1, 4, 5, and 6 in adults, the agency notes.
Sofosbuvir plus ribavirin was evaluated in an open-label study in 50 children aged 12 years and older. All patients with HCV genotype 2 and 97% of those with HCV genotype 3 had undetectable virus 12 weeks after finishing treatment.
Fatigue and headache were the most common adverse reactions observed with sofosbuvir-ribavirin and ledipasvir-sofosbuvir treatment.
Hepatitis B virus (HBV) reactivation has been reported in HCV/HBV-coinfected adults treated with direct-acting antivirals for HCV. Current guidelines from the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America recommend screening patients for HBV infection before beginning treatment with a direct-acting antiviral medication.