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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/199169/2014

EMEA/H/C/000395

EPAR summary for the public

Pegasys

peginterferon alfa-2a

This is a summary of the European public assessment report (EPAR) for Pegasys. It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of use for Pegasys.

What is Pegasys?

Pegasys is a medicine that contains the active substance peginterferon alfa-2a. It is available as a solution for injection in vials (135 and 180 micrograms), pre-filled syringes (90, 135 and 180 micrograms) and pre-filled pens (135 and 180 micrograms).

What is Pegasys used for?

Pegasys is used to treat the following diseases:

•    chronic (long-term) hepatitis B (a disease of the liver due to infection with the hepatitis B virus). It is used in adults who have compensated liver disease (when the liver is damaged but works normally), who also show signs that the virus is still multiplying;

•    chronic hepatitis C (a disease of the liver due to infection with the hepatitis C virus). It is used in combination with other medicines in adults with compensated liver disease. Pegasys may also be used with ribavirin in children 5 years of age or older who have not been treated before, and in whom the benefits of therapy outweigh the risks of reduced growth from treatment.

The medicine can only be obtained with a prescription.

How is Pegasys used?

Treatment with Pegasys should be started by a doctor who has experience in the treatment of hepatitis B or C. Pegasys is given by injection under the skin in the abdomen (tummy) or thigh. In adults it is usually given as 180 micrograms once a week for 48 weeks, although some hepatitis C

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patients may need 16, 24 or 72 weeks of treatment. Children with hepatitis C are generally given 65 to 180 micrograms once a week, according to their height and weight, for 24 or 48 weeks depending on the type of hepatitis C virus.

The dose may need to be adjusted for patients who experience side effects. For further information see the summary of product characteristics (also part of the EPAR).

How does Pegasys work?

The active substance in Pegasys, peginterferon alfa-2a, belongs to the group 'interferons'. Interferons are natural substances produced by the body that help it fight infections caused by viruses. The exact way alfa interferons work in viral diseases in not fully understood, but it is thought that they act as immunomodulators (substances that modify how the immune system, the body's defence system, works). Alfa interferons may also block the multiplication of viruses.

Peginterferon alfa-2a is very similar to interferon alfa-2a, which is widely available in the European Union (EU) as Roferon-A. In Pegasys, the interferon alfa-2a has been 'pegylated' (attached to a chemical called polyethylene glycol). This decreases the rate at which the substance is removed from the body and allows the medicine to be given less often. The interferon alfa-2a in Pegasys is produced by a method known as 'recombinant DNA technology': it is made by bacteria into which a gene (DNA) has been introduced, which makes them able to produce interferon alfa-2a. The replacement acts in same way as naturally produced interferon alfa.

How has Pegasys been studied?

In chronic hepatitis C in adults, Pegasys has been studied on its own in three studies involving a total of 1,441 patients, and in combination with ribavirin in one study involving 1,149 patients. All of these studies lasted 48 weeks, and compared the effectiveness of Pegasys with that of interferon alfa-2a.

Additional studies looked at the combination of Pegasys and the hepatitis C medicine ribavirin in adults with chronic hepatitis C and included: one study comparing two doses and two durations of treatment (24 or 48 weeks) in 1,285 patients; one study comparing 16 and 24 weeks of treatment in 1,469 patients; one study in 514 patients with normal liver enzyme levels; one study in 860 patients who were also infected with HIV; and a final study in 950 patients who did not respond to previous treatment with peginterferon alfa-2b and ribavirin.

Peginterferon alfa-2a has also been studied in combination with telaprevir (a hepatitis C medicine) and ribavirin in 3 main studies involving over 2,000 adult patients, and in combination with boceprevir (another hepatitis C medicine) and ribavirin in 1 main study involving 202 adult patients.

In children with chronic hepatitis C, the effectiveness of 48 weeks of treatment with Pegasys and ribavirin was examined in 55 children in one main study.

In chronic hepatitis B in adults, two studies have been carried out comparing Pegasys with lamivudine (another antiviral medicine) in 820 'HBeAg-positive' patients (infected with the common type of the hepatitis B virus) and in 552 'HBeAg-negative' patients (infected with a virus that has mutated [changed], leading to a form of chronic hepatitis B that is more difficult to treat).

In all cases, the main measure of effectiveness was the disappearance of the markers of hepatitis virus infection from the blood after treatment and/or at 'follow-up' six months later.

What benefit has Pegasys shown during the studies?

In chronic hepatitis C in adults, Pegasys on its own was more effective than interferon alfa-2a. More patients responded to treatment, with 28 to 39% of patients in the Pegasys group having no markers of hepatitis virus infection in their blood at follow-up, compared with 8 to 19% in the interferon alfa-2a group. When it was used in combination with ribavirin in adults, Pegasys was more effective than when it was used on its own (45% responders at follow-up compared with 24%), and was as effective as the combination of interferon alfa-2a and ribavirin (39% responders). The additional adult studies of Pegasys in combination with ribavirin confirmed the effectiveness of Pegasys, including in patients with HIV and those who did not respond to previous treatment.

The adult studies of peginterferon alfa-2a in combination with telaprevir and ribavirin or with boceprevir and ribavirin showed that these combinations significantly increased the proportion of patients who responded to treatment compared with peginterferon alfa-2a plus ribavirin.

The study in children showed similar effectiveness with the combination of Pegasys and ribavirin to that seen in adults treated with Pegasys and ribavirin.

In chronic hepatitis B, Pegasys was more effective than lamivudine in both HBeAg-positive and negative patients. The proportions of patients with no signs of viral activity in their blood at follow-up were 32% with Pegasys and 22% with lamivudine in the HBeAg-positive patients, and 43% with Pegasys and 29% with lamivudine in the HBeAg-negative patients.

What is the risk associated with Pegasys?

The most common side effects with Pegasys (seen in more than 1 patient in 10) are loss of appetite, headache, insomnia (difficulty sleeping), irritability, depression, anxiety, dizziness, impaired concentration, dyspnoea (difficulty breathing), cough, nausea (feeling sick), diarrhoea, abdominal pain (stomach ache), alopecia (hair loss), dermatitis (inflammation of the skin), pruritus (itching), dry skin, myalgia (muscle pain), arthralgia (joint pain), fatigue (tiredness), asthenia (weakness), pyrexia (fever), rigors (shaking chills), reactions at the site of the injection and pain. Children treated with Pegasys and ribavirin also showed reduced growth for their age, which may not be reversible. For the full list of all side effects reported with Pegasys, see the package leaflet.

Pegasys must not be used in people who are hypersensitive (allergic) to alpha interferons or any of the other ingredients. Pegasys must also not be used in:

•    patients with auto-immune hepatitis (when the body's natural defences attack the liver);

•    patients with other severe liver problems;

•    patients with a history of severe heart disease;

•    HIV-infected patients with signs of moderate liver disease;

•    patients taking another antiviral medicine called telbivudine;

•    newborns and children under the age of 3;

•    children with a history of severe psychiatric disorders, especially severe depression or suicidal thinking.

For the full list of restrictions with Pegasys, see the package leaflet.

Why has Pegasys been approved?

The CHMP decided that Pegasys's benefits are greater than its risks and recommended that it be given marketing authorisation.

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

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

Other information about Pegasys

The European Commission granted a marketing authorisation valid throughout the EU for Pegasys on 20 June 2002.

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

This summary was last updated in 05-2014.

Pegasys

EMA/199169/2014

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