This news release from the European Association for the Study of the Liver (EASL) heralding the safety and efficacy of a combination drug therapy for children with hepatitis C does a good job in several areas. It explains the scope of benefits and harms, how the study was conducted, and how the therapy could improve treatment options for kids with this contagious disease. On the other hand, the news release overlooks discussion of the enormous cost of this therapy and of potential adverse effects that may emerge when the therapy is used in a large population. We also disagree with its use of the sensational words “cure” and “breakthrough.”
Editor’s note: This review contains an update under the benefits criteria that adds a caution about not equating reduced viral load with a cure.
One estimate puts the incidence of chronic hepatitis C infection in U.S. children at between 23,000 and 46,000. Pediatric hepatitis C is usually contracted at birth from mothers with a history of IV drug abuse. More than one-third of infected kids eventually develop a life threatening long-term liver disease. Approving more effective and safer treatment options for these kids — options that are already available to adults — would be an important benefit.
There’s no mention of costs. The manufacturer, Gilead Sciences, has been charging $94,500 for a 12-week regimen of this combination therapy, marketed to adults as Harvoni. While government and private payers have balked at the cost, the company says the price tag is justified by its effectiveness in eradicating the virus, which will save the cost of treating serious liver disease down the road.
The news release states that 99 percent, or 89 out of 90, children treated with the ledipasvir/sofosbuvir combination had undetectable levels of hepatitis C virus 12 weeks after treatment.
We do caution that sustained virological response (SVR) and the reduction in viral load, which is what this study measured, may or may not reflect outcomes that people care about. As discussed in another review on a different hepatitis C drug announcement, “Patients care most about conditions that affect them and not how many virus particles are in their blood.”
The news release does an adequate job, stating that the combination therapy “was well-tolerated, and no patients experienced a serious adverse event considered related to the study drug.” It adds: “The most common side effects reported in 10% or more of patients were headache, fever, abdominal pain, diarrhea, vomiting, cough, fatigue, sore throat and nausea.”
But one important caveat wasn’t mentioned: Often negative effects aren’t apparent until after a drug goes on the market and is used by a large and diverse population of patients. For example, if the drug resulted in a fatal complication in 2 out of 100 children, this small study could easily have missed that. It’s risky to call a drug “safe” until it’s been used in a very large number of patients.
This is particularly true when drugs are fast-tracked for approval by the FDA, as Harvoni’s use in children is expected to be. As HealthNewsReview.org reported in January, Harvoni is among the new generation of hepatitis C drugs that are generating serious adverse effects that warrant further scrutiny. Hence, there could be unknown risks in extending this therapy to kids.
The news release gives information about the length of the study, the number of participants, and the study population. It states that most were male, white, and had no prior treatment, and had been infected by their mothers at birth. And it states that this is an open-label study, so no standard treatment or placebo was used as a comparison.
The release doesn’t engage in disease mongering. It notes the prevalence of hepatitis C among children, which “varies from 0.05%-0.36% in the United States and Europe and up to 1.8%-5.8% in some developing countries.” It would have been even better with specific numbers.
The news release says research funding came from the manufacturer, Gilead Sciences, and the National Institutes of Health, and the study authors own stock in Merck. Kudos for transparency.
The news release offers a comparison with the current standard of care: “While direct-acting antivirals have been used to treat and cure adult patients with HCV,4-7 until now children have been mainly treated for 24 to 48 weeks with pegylated interferon plus ribavirin (RBV), an older treatment which causes severe side effects.”
The news release doesn’t explain what hurdles, such as FDA approval, are required to make this therapy available to children.
The news release explains the significance of this study via quotes from two researchers:
“Direct-acting antivirals have transformed the treatment of adults with chronic HCV (hepatitis C), however, studies of these new therapies in children are required,” said Dr. Karen Murray, University of Washington School of Medicine and Seattle Children’s, Seattle, United States, and lead author of the study. “These data establish the use of the oral direct-acting antivirals as an important treatment option in HCV-infected children aged six to 11 years old.”
“This study is a breakthrough for the management of children aged six to 11 years old with Hepatitis C, demonstrating that the new DAA regimen is highly efficacious and, more importantly, safe in this group of HCV-infected children”, said Prof. Frank Tacke, University Hospital Aachen, Germany, and EASL Governing Board Member.
The news release uses two words — “cure” and “breakthrough” — that we advise journalists to avoid because they are imprecise and tend to sensationalize.