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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/33323/2016

EMEA/H/C/002798

EPAR summary for the public

Sovaldi

sofosbuvir

This is a summary of the European public assessment report (EPAR) for Sovaldi. 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 Sovaldi.

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

What is Sovaldi and what is it used for?

Sovaldi is an antiviral medicine that contains the active substance sofosbuvir. It is used to treat chronic (long-term) hepatitis C (an infectious disease that affects the liver, caused by the hepatitis C virus) in adults. Sovaldi is used in combination with other medicines.

How is Sovaldi used?

Sovaldi 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.

Sovaldi is available as 400 mg tablets. The recommended dose is one tablet taken once a day with food. Sovaldi must be used in combination with other medicines used to treat chronic hepatitis C, such as ribavirin or peginterferon alfa and ribavirin. Several varieties (genotypes) of hepatitis C virus exist, and the duration of treatment with Sovaldi will depend on the genotype of the virus and on which medicines are used together with Sovaldi. For further information, see the package leaflet.

How does Sovaldi work?

The active substance in Sovaldi, sofosbuvir, blocks the action of an enzyme called 'NS5B RNA-dependent RNA polymerase' in the hepatitis C virus, which is essential for the virus to multiply. This stops the hepatitis C virus from multiplying and infecting new cells. Sovaldi works against all genotypes of the hepatitis C virus.

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What benefits of Sovaldi have been shown in studies?

Sovaldi was investigated in four main studies involving a total of 1305 patients infected with hepatitis C. In all four 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.

•    The first study involved 327 previously untreated patients who were infected with hepatitis C virus of genotypes 1, 4, 5 or 6, and who were given Sovaldi together with two other antiviral medicines, peginterferon alfa and ribavirin, for 12 weeks. In this study, 91% (296 out of 327) of patients tested negative for hepatitis C 12 weeks after the end of treatment.

•    The second study involved 499 previously untreated patients who had hepatitis C of genotypes 2 or 3. In this study, patients given Sovaldi together with ribavirin for 12 weeks were compared with patients given peginterferon alfa and ribavirin for 16 weeks. Treatment with Sovaldi was as effective (67% patients - 171 out of 256 - tested negative) as peginterferon-based treatment (67% of patients - 162 out of 243).

•    The third study was done in 278 patients with genotypes 2 or 3 hepatitis C virus who could not take or did not want to have treatment with interferon. This study compared 12 weeks of treatment with Sovaldi and ribavirin with placebo (a dummy treatment) and found that 78% (161 out of 207) of patients taking Sovaldi and ribavirin tested negative for hepatitis C 12 weeks after the end of treatment, whereas none of 71 patients taking placebo were free of the virus.

•    The fourth study was done in 201 patients with hepatitis C virus (genotypes 2 or 3) who did not respond to previous treatment with interferon or whose infections came back. This study compared Sovaldi and ribavirin taken for 12 weeks with Sovaldi and ribavirin taken for 16 weeks. In this study, 50% (51 out of 103) of patients taking Sovaldi and ribavirin for 12 weeks tested negative for hepatitis C, whereas 71 % (70 out of 98) of patients treated for 16 weeks tested negative.

Additional studies showed that Sovaldi in combination with ribavirin decreased the risk of infection of the new liver with hepatitis C virus in patients undergoing transplantation, that Sovaldi is also effective in patients infected with both hepatitis C and HIV, and that the outcome of patients with genotype 3 infection could be improved by extending treatment to 24 weeks.

What are the risks associated with Sovaldi?

The most common side effects with Sovaldi in combination with ribavirin and peginterferon alfa were similar to those commonly reported with ribavirin or peginterferon alfa and included fatigue (tiredness), headache, nausea (feeling sick) and insomnia. Sovaldi did not increase the frequency or severity of these side effects. For the full list of side effects, see the package leaflet.

Sovaldi must not be used together with certain medicines that work as 'potent P-glycoprotein inducers' (the antibiotics rifampicin and rifabutin, the herbal remedy St. John's wort, or the epilepsy medicines carbamazepine, phenobarbital and phenytoin). For the full list of restrictions, see the package leaflet.

Why is Sovaldi approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Sovaldi's benefits are greater than its risks and recommended that it be approved for use in the EU. The CHMP considered that adding Sovaldi to standard treatment is of benefit to patients. Sovaldi allows the infection to be cleared without the patient having to take peginterferon alfa or with only short courses of this medicine (which may cause serious side effects and is not well tolerated by many patients).

The Committee also considered that, if given before a liver transplant, Sovaldi in combination with ribavirin can prevent re-infection of the liver, which in the absence of treatment occurs nearly always and results in a poor prognosis. In addition, virus resistance to Sovaldi is very uncommon and Sovaldi works against all types of hepatitis C virus.

Regarding safety, the Committee noted that, although there is limited information in some patient populations such as those with decompensated liver disease (where the liver is damaged and no longer works properly), no side effects specific to Sovaldi have been identified, and those observed are mainly due to combined treatment with ribavirin or interferons.

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

A risk management plan has been developed to ensure that Sovaldi 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 Sovaldi, including the appropriate precautions to be followed by healthcare professionals and patients.

Other information about Sovaldi

The European Commission granted a marketing authorisation valid throughout the European Union for Sovaldi on 16 January 2014.

The full EPAR for Sovaldi 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 Sovaldi, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 02-2016.

Sovaldi

EMA/33323/2016

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