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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/277000/2016

EMEA/H/C/003850

EPAR summary for the public

Harvoni

ledipasvir / sofosbuvir

This is a summary of the European public assessment report (EPAR) for Harvoni. It explains how the Agency assessed the medicine to recommend its authorisation in the EU and its conditions of use. It is not intended to provide practical advice on how to use Harvoni.

For practical information about using Harvoni, patients should read the package leaflet or contact their doctor or pharmacist.

What is Harvoni and what is it used for?

Harvoni is an antiviral medicine used to treat adults with chronic (long-term) hepatitis C (an infectious disease that affects the liver, caused by the hepatitis C virus).

Harvoni contains the active substances ledipasvir and sofosbuvir.

How is Harvoni used?

Harvoni can only be obtained with a prescription and treatment should be started and monitored by a doctor experienced in the management of patients with chronic hepatitis C.

Harvoni is available as tablets which contain 90 mg ledipasvir and 400 mg sofosbuvir. The recommended dose is one tablet taken once a day. There are several varieties (called genotypes) of hepatitis C virus and Harvoni is recommended for use in patients with virus of genotypes 1, 4, 5 and 6 and for some patients with genotype 3. The duration of treatment with Harvoni and whether it is used alone or in combination with another medicine called ribavirin depends on the genotype of the virus and the nature of the liver problems patients have, for example if they have liver cirrhosis (scarring) or their liver is not working properly. For further information, see the summary of product characteristics (also part of the EPAR).

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How does Harvoni work?

The active substances in Harvoni, ledipasvir and sofosbuvir, block two proteins essential for the hepatitis C virus to multiply. Sofosbuvir blocks the action of an enzyme called 'NS5B RNA-dependent RNA polymerase', while ledipasvir targets a protein called 'NS5A'. By blocking these proteins, Harvoni stops the hepatitis C virus from multiplying and infecting new cells.

Sofosbuvir has been authorised as Sovaldi since January 2014.

What benefits of Harvoni have been shown in studies?

Harvoni was investigated in three main studies involving a total of around 2,000 patients infected with hepatitis C of genotype 1 who did not have failure of liver function. In all three studies, the main measure of effectiveness was the number of patients whose blood tests did not show any sign of hepatitis C virus 12 weeks after the end of treatment.

In these studies, patients were given Harvoni, with or without ribavirin, for 8, 12 or 24 weeks, depending on the characteristics of the patients. Around 94% to up to 99% of patients given Harvoni alone tested negative for the virus 12 weeks after the end of treatment. The addition of ribavirin was not needed for most patients.

Results of the studies also showed that patients who have compensated cirrhosis (scarring of the liver but who maintained liver function) had a higher likelihood of clearing the virus when treatment was extended to 24 weeks. Patients whose infection was resistant to other antiviral medicines could also benefit from extending treatment to 24 weeks.

Supportive data showed that Harvoni in combination with ribavirin would be of benefit for some patients with genotype 3 virus. Benefit was also shown for patients with genotype 1, 4, 5 and 6 with or without cirrhosis and/or for those who had received a liver transplant.

What are the risks associated with Harvoni?

The most common side effects with Harvoni (which may affect more than 1 in 10 people) are tiredness and headache. Harvoni must not be used together with the cholesterol medicine rosuvastatin. It must also not be used together with the following medicines known as potent P-gp inducers as these can reduce the effects of Harvoni :

•    rifampicin;

•    rifabutin;

•    carbamazepine;

•    phenobarbital;

•    phenytoin and

St John's wort (a herbal preparation used to treat depression).

For the full list of all side effects and restrictions with Harvoni, see the package leaflet.

Why is Harvoni approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Harvoni's benefits are greater than its risks and recommended that it be approved for use in the EU. The CHMP considered that treatment with Harvoni, with or without ribavirin, is of high benefit to many patients

Harvoni

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with hepatitis C virus, including those who have had a liver transplant and/or who have compensated cirrhosis. Although studies are limited in patients with decompensated cirrhosis, these patients may benefit from extended treatment with Harvoni and ribavirin. Regarding safety, the treatment is well tolerated.

What measures are being taken to ensure the safe and effective use of Harvoni?

A risk management plan has been developed to ensure that Harvoni is used as safely as possible.

Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Harvoni, including the appropriate precautions to be followed by healthcare professionals and patients.

Further information can be found in the summary of the risk management plan.

Other information about Harvoni

The European Commission granted a marketing authorisation valid throughout the European Union for Harvoni on 17 November 2014.

The full EPAR and risk management plan summary for Harvoni can be found on the Agency's website: ema.europa.eu/Find medicine/Human medicines/European public assessment reports. For more information about treatment with Harvoni, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 05-2016.

Harvoni

EMA/277000/2016