Tag Archives: pibrentasvir

Oral Pan-Genotypic HCV Drugs Approved For Children Starting at Age 3 Years

Posted on by

AAP News (Nov 2021): First oral pan-genotypic HCV drugs approved for children as young as 3 years

“The Food and Drug Administration (FDA) has approved Epclusa (sofosbuvir and velpatasvir) and Mavyret (glecaprevir and pibrentasvir) for treatment of chronic hepatitis C virus (HCV) infection in pediatric patients as young as 3 years. These products are the first all-oral, pan-genotypic (genotypes 1-6) HCV treatment regimens for pediatric patients 3 years and older…Both products are available as oral tablets and as newly approved oral pellets in dosing strengths suitable to accommodate the recommended weight-based dosing in pediatric patients.”

From HCVGuidelines.org (updated September 2021):

The following images are from Abbvie patient-provider handouts. I do not receive any funding from any pharmaceutical company but think these instructions are useful.

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Liver Shorts -November 2020 and Georgia’s ACA Waiver

Posted on by

E Zuckerman et al. Clin Gastroenterol Hepatol 2020; 18: 2544-53. Full text link: Eight Weeks of Treatment With Glecaprevir/Pibrentasvir Is Safe and Efficacious in an Integrated Analysis of Treatment-Naïve Patients With Hepatitis C Virus Infection

  • “We pooled data from 8 phase 2 or phase 3 trials of treatment-naïve patients with HCV genotype 1 to 6 infections, without cirrhosis or with compensated cirrhosis, who received 8 weeks of glecaprevir/pibrentasvir.” (n=1248) Key finding:  Overall rates of sustained virologic response at post-treatment week 12 were 97.6% (1218 of 1248) in the intention to treat (ITT) and 99.3% (1218 of 1226) in the modified ITT populations.

JA Silverman et al. JPGN 2020; 71: 283-287. Composite Lipid Emulsion for the Infant at Risk of Intestinal Failure–associated Liver Disease: The Canadian Perspective

This review discussed the use of SMOFlipid that includes soybean, medium-chain triglycerides, olive and fish oils. Key points:

  • “Lipid minimization strategies have also been shown to reverse IFALD [intestinal failure associated liver disease]. There are, however, considerable concerns regarding adequate weight gain, compromise to neurodevelopment, and EFAD [essential fatty acid deficiency]”
  • “Thee is actually considerable safety data for CLE [composite lipid emulsion] in neonates, albeit over the short term.”
  • “In Canada, CLE is currently the lipid emulsion of choice for all infants at risk of IFLAD.”

T Mitchell et al. Clin Gastroenterol Hepatol 2020; 18: 1584-1591. Decreased Physical Working Capacity in Adolescents With Nonalcoholic Fatty Liver Disease Associates With Reduced Iron Availability

  • Methods: “We collected information on weight-adjusted, submaximal physical work capacity (PWC), ultrasound-determined hepatic steatosis, iron indices, and hematologic and metabolic parameters from 390 female and 458 male participants of the Raine Study—a longitudinal study of disease development … in Western Australia”
  • Key finding: “Fourteen percent of the cohort had NAFLD. PWC was significantly reduced in adolescents with NAFLD compared to adolescents without NAFLD (reduction of 0.17 W/kg, P = .0003, adjusted for sex and body mass index [BMI])… we found NAFLD to be associated with decreased cardiorespiratory fitness, independent of BMI. The relationship between transferrin saturation and PWC in adolescents with NAFLD indicates that functional iron deficiency might contribute to reductions in cardiorespiratory fitness.”

In other news, Georgia has received approval for an affordable care act waiver. From the AJC (October 15, 2020): Kemp’s health care waivers win federal approval Two key points:

  • “Thousands of Georgia’s poor and uninsured adults who meet a work or activity requirement will soon be eligible for Medicaid, with perhaps 50,000 added to the rolls within two years…And more than 350,000 very poor, uninsured Georgia adults still won’t meet Georgia’s requirements for Medicaid”
  • “At the same time, the 400,000 Georgians who bought individual health insurance plans on the federal healthcare.gov Affordable Care Act shopping website will find they can’t do that anymore. Instead they will be directed to contact information for private brokers or insurance companies”
These tweets were posted on 11/2/20.

“Crushing it:” Practice Guidance for Hepatitis C

Posted on by

Today’s post on Hepatitis C follows a few screenshots from twitter regarding the coronavirus epidemic.

Pediatric report of coronavirus in children: NEJM Full link: SARS-CoV-2 Infection in Children A recent review of 72,314 cases by the Chinese Center for Disease Control and Prevention showed that less than 1% of the cases were in children younger than 10 years of age (n=171)…3 patients required intensive care support and invasive mechanical ventilation; all had coexisting conditions. There was one death in a 10-month-old child with intussusception had multiorgan failure and died 4 weeks after admission.

——-

As noted yesterday, this post will review a recent practice guidance for hepatitis C

Some specific recommendations for children:

Testing:

  • “All children born to HCV-infected women should be tested for HCV infection. Testing is recommended using an antibody-based test at or after 18 months of age.”
  • “Testing with an HCV-RNA assay can be considered in the first year of life, but the optimal timing of such testing is unknown” (but can be done as early as 2 months of life).
  • “The siblings of children with vertically-acquired chronic HCV should be tested for HCV infection, if born from the same mother.”

Counseling for parents:

  • “Parents should be informed that hepatitis C is not transmitted by casual contact and, as such, children with HCV infection do not pose a risk to other children and can participate in school, sports, and athletic activities, and engage in all other regular childhood activities without restrictions.”
  • “Parents should be informed that universal precautions should be followed at school and in the home of children with HCV infection. Educate families and children about the risk and routes of HCV transmission, and the techniques for avoiding blood exposure, such as avoiding the sharing of toothbrushes, razors, and nail clippers, and the use of gloves and dilute bleach to clean up blood.”

Treatment:

  • “Direct-acting antiviral (DAA) treatment with an approved regimen is recommended for all children and adolescents with HCV infection aged ≥3 years as they will benefit from antiviral therapy, regardless of disease severity.”
  • Early treatment in childhood is expected to be cost-effective compared to treatment at later ages based on previous studies

This chart provides recommendations for pediatric patients who have not received prior direct-acting antivirals. More information at HCVguidelines.org

“Crushing it:” Two More Pediatric Hepatitis C Trials

Posted on by

Before today’s planned blog post, I wanted to mention a good NY Times article which highlights how long the virus which causes COVID-19 can be present on surfaces:

Full link from NY Times: How Long Will Coronavirus Live on Surfaces or in the Air Around You?

An excerpt:

The virus lives longest on plastic and steel, surviving for up to 72 hours. But the amount of viable virus decreases sharply over this time. It also does poorly on copper and cardboard, surviving four to eight hours; the latter finding suggests packages that arrive in the mail should be safe — unless the delivery person has coughed or sneezed on it or has handled it with contaminated hands.

That the virus can survive and stay infectious in aerosols is also important for health care workers.

For weeks experts have maintained that the virus is not airborne. But in fact, it can travel through the air and stay suspended for that period of about a half-hour.

The virus does not linger in the air at high enough levels to be a risk to most people who are not physically near an infected person. But the procedures health care workers use to care for infected patients are likely to generate aerosols.

The original article from NEJM:  Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1

——–

This “C” virus was hard to cure until recently.  More good news from recently published studies for pediatric hepatitis c virus (HCV) treatment:

  • KB Schwarz et al. Hepatology 2020; 71: 422-30. 
  • MM Jonas et al. Hepatology 2020; 71: 456-62.
  • AASLD-IDSA Practice Guidance Panel. Hepatology 2020; 71: 686-721

In the first study of an all oral regimen of ledipasvir-sofosbuvir, sustained virological response at 12 weeks after dosing (SVR12) was achieved in 33 of 34 (97%) of children 3-<6 yrs of age with genotypes 1 or 4 (only 1 with type 4). No serious adverse effects were reported. Dosing: 33.75 mg/150 mg if <17 kg or 45 mg/200 mg if ≥17 kg. The one non-responder discontinued treatment due to drug taste.  Pharmokinetic studies in 13 patients confirmed appropriate medication dosing.

In the second study of glecaprevir/pibrentasvir (G/P), as part of the DORA phase 2/3 nonrandomized, open-label trial, adolescents 12-17 received the ‘adult’ regimen of 300 mg/120 mg daily for 8-12 weeks in accordance with indication duration based on adult data.  Among the 47 patients (genotypes 1, 2, 3, 4), 100% achieved SVR12. Safety profile was consistent with prior studies in adults.

The third publication, which is quite lengthy, highlights updated recommendations for HCV in adults and children (this will be reviewed in tomorrow’s post).

Related blog posts:

Liver Briefs -July 2019

Posted on by

NH Ebel et al. JPGN 2019; 68: 788-92.  Hepatic venous pressure gradient (HVPG) did not correlate with the risk of complications from portal hypertension in this pediatric cohort (n=41); this is in contrast to studies in adults showing the utility of HVPG measurements.

AG Singal et al. Gastroenterol 2019; 156: 2149-57. AGA Practice Update on Direct-Acting Antivirals for Hepatitis C and Hepatocellular Carcinoma. There are 12 best practice advice –here are the first three:

  • BEST PRACTICE ADVICE 1: DAA treatment is associated with a reduction in the risk of incident HCC. The relative risk reduction is similar in patients with and without cirrhosis.
  • BEST PRACTICE ADVICE 2: Patients with advanced liver fibrosis (F3) or cirrhosis should receive surveillance imaging before initiating DAA treatment.
  • BEST PRACTICE ADVICE 3: Patients with advanced liver fibrosis (F3) or cirrhosis at the time of DAA treatment represent the highest-risk group for HCC after DAA-induced sustained virologic response. These patients should stay in HCC surveillance

N Hamdane et al. Gastroenterol 2019; 156: 2313-29. This study found that chronic HCV infection induced specific genome-wide-changes in H3K27ac which correlated with expression of mRNAs and proteins.  These epigenetic changes persisted after an SVR to DAAs or interferon-based therapies. These changes could explain some of the reason why HCC remains a risk after successful treatment with DAAs.

DT Dieterich et al. Gastroenteroloy & Hepatology 2019; 15S: 3-11 Link: “A simplified algorithm for the management of Hepatitis C Infection”  An excerpt:

“The algorithm begins with universal HCV screening and diagnosis by testing for HCV antibody with reflex to polymerase chain reaction to detect HCV RNA. The pretreatment evaluation uses platelet-based stratification to initially assess fibrosis, and the pan-genotypic regimens glecaprevir/pibrentasvir or sofosbuvir/velpatasvir are recommended for treatment. Unless clinically indicated, on-treatment monitoring is optional. Confirmation of cure (undetectable HCV RNA 12 weeks posttreatment) is followed by harm-reduction measures, as well as surveillance for hepatocellular carcinoma every 6 months in patients with advanced fibrosis/cirrhosis.”  My take: This algorithm is much simpler than the expanded recommendations from HCVguidelines.org website, though these agents, to my knowledge, do not yet have a pediatric indication.

 

Glecaprevir-Pibrentasvir for Hepatitis C Infections

Posted on by

Before discussing one of the newest therapies for Hepatitis C, I wanted to give a shout out to Barbara McElhanon who along with Joanna Lomas-Mevers provided a quick update to our group on their important research to improve the management of encopresis in children with autism spectrum disorders.

Last August, the FDA announced approval of glecaprevir-pibrentasvir as a pangenomic treatment for Hepatitis C (From blog: Eight Week Pangenomic HCV Treatment Approved).

However, it is only in this past two weeks that some of the data from two large randomized, open-label, multicenter trials have been published: Z Zeuzem et al. NEJM 2018; 378: 354-69.  In total, 1208 patients were treated in the “ENDURANCE-1” and “ENDRUANCE-3” trials.

Key findings:

  • For genotype 1-infected patients, glecaprevir-pibrentasvir resulted in a sustained virologic response rate (at week 12) of 99.1% in the 8-week group and 99.7% in the 12-week group.
  • For genotype 3, glecaprevir-pibrentasvir resulted in a sustained virologic response rate (at week 12) of 95% with both 8-week and 12-week treatment.  A comparison group of sofosbuvir-daclatasvir (12 week treatment) resulted in a sustained virologic response rate (at week 12) of 97%.
  • Serious adverse events were rare.  There were three patients who died during the post-treatment period: two from heroin overdoses and one from ethanol intoxication/methadone toxicity.  Headache and fatigue were the most common reported adverse events.
  • There were no relapses among HCV-1-infected patients who were treated for 8 weeks

In addition to these studies, “recent phase 3 trials have shown that an 8-week regimen of glecaprevir-pibrentasvir in patients without cirrhosis” yielded response of 98% for genotype 2 and 93% for genotypes 4, 5, and 6.

My take: These studies indicate that glecaprevir-pibrentasvir is an effective 8-week therapy for patients with HCV infection.  Despite this terrific advance, unless we find a way to address the opioid crisis which is triggering an HCV epidemic, I am not optimistic that there will be an improvement in the number of individuals with HCV infection.

Related blog posts:

Eight Week Pangenomic HCV Treatment Approved

Posted on by

FDA Announcement Aug 3, 2017: FDA approves Mavyret for Hepatitis C

An excerpt:

The U.S. Food and Drug Administration today approved Mavyret (glecaprevir and pibrentasvir) to treat adults with chronic hepatitis C virus (HCV) genotypes 1-6 without cirrhosis (liver disease) or with mild cirrhosis, including patients with moderate to severe kidney disease and those who are on dialysis. Mavyret is also approved for adult patients with HCV genotype 1 infection who have been previously treated with a regimen either containing an NS5A inhibitor or an NS3/4A protease inhibitor but not both. 

Mavyret is the first treatment of eight weeks duration approved for all HCV genotypes 1-6 in adult patients without cirrhosis who have not been previously treated. Standard treatment length was previously 12 weeks or more.

Related blog posts:

Gravelly Point, Arlington, VA