Introduction

The fixed combination ledipasvir / sofosbuvir (trade name: Harvoni) has been approved in Germany since July 2017 for the treatment of hepatitis C in teenagers aged 12 and over. This treatment aims to stop the virus from multiplying and prevent hepatitis C complications.

Hepatitis C viruses (HCVs) attack the liver, where they can cause acute inflammation. There are seven known forms of hepatitis C viruses, referred to as genotypes 1 to 7. In up to 80 out of 100 people with hepatitis C, the immune system is unable to successfully fight the virus on its own. These people develop a permanent (chronic) inflammation of the liver which can cause cirrhosis. The liver then gradually loses its ability to work well.

As long as the effect on liver performance isn't noticeable, it's known as “compensated cirrhosis." Signs of advanced ("decompensated") cirrhosis include fluid retention in the abdominal cavity, blood clotting problems, and neurological and psychiatric problems, sometimes even as severe as a coma. The risk of liver cancer increases too. It is currently believed that a treatment can reduce the risk of such complications if patients consistently have no detectable virus in their blood following that treatment.

The fixed combination ledipasvir / sofosbuvir has only been approved for the treatment of chronic hepatitis C genotypes 1, 3, 4, 5 and 6.

Application

Ledipasvir / sofosbuvir is taken once a day in the form of a tablet, independently of meals. One tablet contains 90 mg of ledipasvir and 400 mg of sofosbuvir. The length of treatment is determined by the type and severity of problems, and can last between 8 and 24 weeks. Depending on the course of disease, the drug may be combined with ribavirin.

Other treatments

For teenagers with hepatitis C who haven't had treatment before, the standard treatment is a combination of peginterferon alfa and ribavirin.

Teenagers with hepatitis C who have had unsuccessful treatment before receive best supportive care (BSC). This should be tailored to the patient's individual needs with the aim of relieving symptoms such as pain, and improving quality of life.

Assessment

In late 2017, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) looked into the advantages and disadvantages of the fixed combination ledipasvir / sofosbuvir compared with the standard treatments for hepatitis C in teenagers.

The manufacturer gave IQWiG one study that provided at least preliminary answers to some questions. The study looked into treatment with ledipasvir / sofosbuvir, but didn't compare it directly with another treatment. The results of this kind of study generally aren't very conclusive when used to compare different treatments. But the researchers at IQWiG still used the study for the assessment because there's currently no evidence that any other treatments are as effective.

People with chronic hepatitis C can be divided into different groups based on the genotype of their virus, the stage of the disease, and their previous treatments. The study provided data on two groups of teenagers with genotype 1 chronic hepatitis C:

  • Teenagers with chronic hepatitis C (genotype 1) without liver cirrhosis or with compensated liver cirrhosis who have had unsuccessful treatment.
  • Teenagers with chronic hepatitis C (genotype 1) without liver cirrhosis or with compensated liver cirrhosis who have not had any other treatment.

The researchers at IQWiG analyzed the data of 100 teenagers: 80 of them hadn't had treatment before, while 20 had had unsuccessful treatment. All of the teenagers took one tablet of ledipasvir / sofosbuvir per day for 12 weeks.

What advantages does ledipasvir / sofosbuvir have?

Complications: The study didn't last long enough to be able to assess the effect of ledipasvir / sofosbuvir on potential complications such as liver cancer. But early estimates suggest that ledipasvir / sofosbuvir offers an advantage here:

  • In about 98 out of 100 teenagers who hadn't had treatment before, no viruses were detectable in their blood 24 weeks after the treatment ended.
  • This was the case in all of the teenage who had had unsuccessful treatment before.

Such positive results aren't to be expected from the standard treatments. But it's not possible to tell exactly how big this advantage of ledipasvir / sofosbuvir actually is.

No difference

Serious side effects: According to preliminary analyses, treatment with ledipasvir / sofosbuvir has no significant disadvantages here compared with the standard treatment. The people in the study didn't have any severe side effects.

What remains unanswered?

Quality of life: The study didn't look into quality of life.

More information

This information summarizes the main results of a review produced by the Institute for Quality and Efficiency in Health Care (IQWiG, Germany). The review was commissioned by the German Federal Joint Committee (G-BA) as part of the “early benefit assessment of medications.” On the basis of this review and the hearings received, G-BA passed a resolution on the added benefit of ledipasvir / sofosbuvir (Harvoni).