VIDEO: Harvoni shows safety, efficacy in adolescents for hepatitis C

 

MONTREAL – One of the antiviral drug combinations that has revolutionized treatment of hepatitis C virus in adults has for the first time been shown safe and effective against genotype 1 infections in adolescents aged 12-17 years old, paving the way to new regulatory labeling followed by easier and more reliable payer coverage for definitive hepatitis C treatment in this age group.

“I think having clear data on safety and efficacy and FDA [Food and Drug Administration] approval will greatly help getting insurance coverage,” for the tested combination of ledipasvir/sofosbuvir (Harvoni) Karen F. Murray, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

Mitchel L. Zoler/Frontline Medical News

Beyond the coverage and labeling issues, the results from this 100-patient, open-label study are important because “children’s metabolisms are different and you can see toxicities that you don’t see in adults from this novel set of drugs,” said Dr. Murray, chief of gastroenterology and hepatology at Seattle Children’s Hospital and professor of medicine at the University of Washington.

The results showed that in adolescents the ledipasvir/sofosbuvir formulation tested, at the same dosage approved for adults, was “very potent for genotype 1 hepatitis C, and was not only well tolerated but very easy” when given for 12 weeks, Dr. Murray said in an interview. The nearly perfect score for sustained virologic responses was “spectacular,” she added.

Ongoing studies that should finish soon are also looking at the safety and efficacy of ledipasvir/sofosbuvir in children aged 3-11 years old and in children and adolescents infected by other hepatitis C genotypes, specifically 4, 5, and 6. Taking on genotypes 2 and 3 will require additional treatment with ribavirin, she noted. Subsequent reports will also document patient outcomes 24 weeks from the start of treatment, after they’ve been off their completed regimen for 12 weeks. Gilead staffers have told Dr. Murray that they anticipate asking the FDA before the end of 2016 for approval to relabel the ledipasvir/sofosbuvir formulation they market to include adolescents, and possibly children too, depending on the outcome of studies still underway.

The result she reported came from 100 patients enrolled at 24 centers in the United States, Canada, and Europe. They averaged 15 years old, nearly two-thirds were girls, and 90% were white. One-fifth of the patients had been previously treated, and 81% were infected by genotype 1a hepatitis C with the remaining 19% infected with genotype 1b. Patients received the conventional, marketed formulation of ledipasvir/sofosbuvir, 90/400 mg, orally once daily.

Ninety-eight of the patients had no detectable hepatitis C virus in their blood at the end of 12 weeks of treatment. The other two patients were lost to follow-up and did not undergo virologic testing at the end of treatment and conservatively were tallied as nonresponders, she reported. A pharmacokinetic study done in a subgroup of patients showed plasma drug levels comparable with those seen in adults.

Although 71% of the patients reported having some adverse effect, no patient reported a serious or grade 3 or 4 adverse effect and no patient stopped treatment because of adverse effects. Nine patients had a grade 3 or 4 laboratory abnormality on treatment. The only lab abnormality to occur in more than one patient was a transient rise in amylase levels, which happened in three patients. The regimen’s overall performance in adolescents closely tracked what’s been seen in adults, Dr. Murray said.

“These data will lead to FDA approval” of the regimen for adolescents, she said confidently, and that will ease insurance coverage. “There will still be hoops to jump through, but with approval and once written into guidelines, insurers will be under pressure to reimburse for it,” she noted. “We find that, because of the cost, insurers resist or refuse to pay for these medications. The idea of treating only patients with advanced liver disease is morally inappropriate. These children must be treated before they develop significant or irreversible liver disease.”

[email protected]

On Twitter @mitchelzoler

 

MONTREAL – One of the antiviral drug combinations that has revolutionized treatment of hepatitis C virus in adults has for the first time been shown safe and effective against genotype 1 infections in adolescents aged 12-17 years old, paving the way to new regulatory labeling followed by easier and more reliable payer coverage for definitive hepatitis C treatment in this age group.

“I think having clear data on safety and efficacy and FDA [Food and Drug Administration] approval will greatly help getting insurance coverage,” for the tested combination of ledipasvir/sofosbuvir (Harvoni) Karen F. Murray, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

Mitchel L. Zoler/Frontline Medical News

Beyond the coverage and labeling issues, the results from this 100-patient, open-label study are important because “children’s metabolisms are different and you can see toxicities that you don’t see in adults from this novel set of drugs,” said Dr. Murray, chief of gastroenterology and hepatology at Seattle Children’s Hospital and professor of medicine at the University of Washington.

The results showed that in adolescents the ledipasvir/sofosbuvir formulation tested, at the same dosage approved for adults, was “very potent for genotype 1 hepatitis C, and was not only well tolerated but very easy” when given for 12 weeks, Dr. Murray said in an interview. The nearly perfect score for sustained virologic responses was “spectacular,” she added.

Ongoing studies that should finish soon are also looking at the safety and efficacy of ledipasvir/sofosbuvir in children aged 3-11 years old and in children and adolescents infected by other hepatitis C genotypes, specifically 4, 5, and 6. Taking on genotypes 2 and 3 will require additional treatment with ribavirin, she noted. Subsequent reports will also document patient outcomes 24 weeks from the start of treatment, after they’ve been off their completed regimen for 12 weeks. Gilead staffers have told Dr. Murray that they anticipate asking the FDA before the end of 2016 for approval to relabel the ledipasvir/sofosbuvir formulation they market to include adolescents, and possibly children too, depending on the outcome of studies still underway.

The result she reported came from 100 patients enrolled at 24 centers in the United States, Canada, and Europe. They averaged 15 years old, nearly two-thirds were girls, and 90% were white. One-fifth of the patients had been previously treated, and 81% were infected by genotype 1a hepatitis C with the remaining 19% infected with genotype 1b. Patients received the conventional, marketed formulation of ledipasvir/sofosbuvir, 90/400 mg, orally once daily.

Ninety-eight of the patients had no detectable hepatitis C virus in their blood at the end of 12 weeks of treatment. The other two patients were lost to follow-up and did not undergo virologic testing at the end of treatment and conservatively were tallied as nonresponders, she reported. A pharmacokinetic study done in a subgroup of patients showed plasma drug levels comparable with those seen in adults.

Although 71% of the patients reported having some adverse effect, no patient reported a serious or grade 3 or 4 adverse effect and no patient stopped treatment because of adverse effects. Nine patients had a grade 3 or 4 laboratory abnormality on treatment. The only lab abnormality to occur in more than one patient was a transient rise in amylase levels, which happened in three patients. The regimen’s overall performance in adolescents closely tracked what’s been seen in adults, Dr. Murray said.

“These data will lead to FDA approval” of the regimen for adolescents, she said confidently, and that will ease insurance coverage. “There will still be hoops to jump through, but with approval and once written into guidelines, insurers will be under pressure to reimburse for it,” she noted. “We find that, because of the cost, insurers resist or refuse to pay for these medications. The idea of treating only patients with advanced liver disease is morally inappropriate. These children must be treated before they develop significant or irreversible liver disease.”

[email protected]

On Twitter @mitchelzoler

 

MONTREAL – One of the antiviral drug combinations that has revolutionized treatment of hepatitis C virus in adults has for the first time been shown safe and effective against genotype 1 infections in adolescents aged 12-17 years old, paving the way to new regulatory labeling followed by easier and more reliable payer coverage for definitive hepatitis C treatment in this age group.

“I think having clear data on safety and efficacy and FDA [Food and Drug Administration] approval will greatly help getting insurance coverage,” for the tested combination of ledipasvir/sofosbuvir (Harvoni) Karen F. Murray, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

Mitchel L. Zoler/Frontline Medical News

Beyond the coverage and labeling issues, the results from this 100-patient, open-label study are important because “children’s metabolisms are different and you can see toxicities that you don’t see in adults from this novel set of drugs,” said Dr. Murray, chief of gastroenterology and hepatology at Seattle Children’s Hospital and professor of medicine at the University of Washington.

The results showed that in adolescents the ledipasvir/sofosbuvir formulation tested, at the same dosage approved for adults, was “very potent for genotype 1 hepatitis C, and was not only well tolerated but very easy” when given for 12 weeks, Dr. Murray said in an interview. The nearly perfect score for sustained virologic responses was “spectacular,” she added.

Ongoing studies that should finish soon are also looking at the safety and efficacy of ledipasvir/sofosbuvir in children aged 3-11 years old and in children and adolescents infected by other hepatitis C genotypes, specifically 4, 5, and 6. Taking on genotypes 2 and 3 will require additional treatment with ribavirin, she noted. Subsequent reports will also document patient outcomes 24 weeks from the start of treatment, after they’ve been off their completed regimen for 12 weeks. Gilead staffers have told Dr. Murray that they anticipate asking the FDA before the end of 2016 for approval to relabel the ledipasvir/sofosbuvir formulation they market to include adolescents, and possibly children too, depending on the outcome of studies still underway.

The result she reported came from 100 patients enrolled at 24 centers in the United States, Canada, and Europe. They averaged 15 years old, nearly two-thirds were girls, and 90% were white. One-fifth of the patients had been previously treated, and 81% were infected by genotype 1a hepatitis C with the remaining 19% infected with genotype 1b. Patients received the conventional, marketed formulation of ledipasvir/sofosbuvir, 90/400 mg, orally once daily.

Ninety-eight of the patients had no detectable hepatitis C virus in their blood at the end of 12 weeks of treatment. The other two patients were lost to follow-up and did not undergo virologic testing at the end of treatment and conservatively were tallied as nonresponders, she reported. A pharmacokinetic study done in a subgroup of patients showed plasma drug levels comparable with those seen in adults.

Although 71% of the patients reported having some adverse effect, no patient reported a serious or grade 3 or 4 adverse effect and no patient stopped treatment because of adverse effects. Nine patients had a grade 3 or 4 laboratory abnormality on treatment. The only lab abnormality to occur in more than one patient was a transient rise in amylase levels, which happened in three patients. The regimen’s overall performance in adolescents closely tracked what’s been seen in adults, Dr. Murray said.

“These data will lead to FDA approval” of the regimen for adolescents, she said confidently, and that will ease insurance coverage. “There will still be hoops to jump through, but with approval and once written into guidelines, insurers will be under pressure to reimburse for it,” she noted. “We find that, because of the cost, insurers resist or refuse to pay for these medications. The idea of treating only patients with advanced liver disease is morally inappropriate. These children must be treated before they develop significant or irreversible liver disease.”

[email protected]

On Twitter @mitchelzoler