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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/225378/2016

EMEA/H/C/001131

EPAR summary for the public

Arzerra

ofatumumab

This document is a summary of the European Public Assessment Report (EPAR) for Arzerra. 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 Arzerra.

What is Arzerra?

Arzerra is a cancer medicine that contains the active substance ofatumumab. It is available as a concentrate that is made up into a solution for infusion (drip) into a vein.

What is Arzerra used for?

Arzerra is used to treat chronic lymphocytic leukaemia (CLL), a cancer of a type of white blood cells called lymphocytes. It is used together with chlorambucil or bendamustine (other cancer medicines) in previously untreated patients who cannot be treated with therapy based on another cancer medicine, fludarabine. It can also be used in patients whose disease has not responded to previous treatment with fludarabine and a medicine called alemtuzumab.

Because the number of patients with CLL is low, the disease is considered 'rare', and Arzerra was designated an 'orphan medicine' (a medicine used in rare diseases) on 7 November 2008.

The medicine can only be obtained with a prescription.

How is Arzerra used?

Arzerra should be given under the supervision of a doctor who has experience in treating cancer and in a place where facilities for resuscitating patients are readily available.

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© European Medicines Agency, 2016. Reproduction is authorised provided the source is acknowledged.

Arzerra is given using an infusion pump. In previously untreated patients, the first Arzerra infusion should contain 300 mg on day 1, followed 7 days later by 1,000 mg. All subsequent infusions (which should be between 2 and 11 more infusions) should contain 1,000 mg given once a month.

In patients who did not respond to previous treatment, the first Arzerra infusion should contain 300 mg, and the following 7 infusions should contain 2,000 mg given once a week. This is followed by a gap of four to five weeks, after which the patient is given an infusion of 2,000 mg once a month for four months.

Before each infusion, the patient is treated with medicines, such as corticosteroids, antihistamines and paracetamol, to help to prevent infusion reactions (such as rash, fever, allergic reactions and difficulty breathing). To reduce the risk of these reactions, infusions are started slowly (particularly when first starting treatment) and then speeded up every 30 minutes if no reactions occur. If reactions do occur, treatment should be interrupted and restarted at a slower rate when the patient has recovered. For more information on how to use Arzerra, see the summary of product characteristics (also part of the EPAR).

How does Arzerra work?

The active substance in Arzerra, ofatumumab, is a monoclonal antibody. A monoclonal antibody is an antibody (a type of protein) that has been designed to recognise and attach to a specific structure (called an antigen) that is found in certain cells in the body. Ofatumumab has been designed to attach to a protein called CD20 that is found on the surface of lymphocytes, including the cancerous lymphocytes seen in CLL. By attaching to CD20, ofatumumab stimulates the body's immune system to attack the cancerous cells, helping to control the disease.

How has Arzerra been studied?

Arzerra has been investigated in one main study involving 223 patients with CLL whose disease had not responded to previous treatment. In 95 of these patients, the disease had not responded to both fludarabine and alemtuzumab, and in 112, treatment with fludarabine had failed but they had not been treated with alemtuzumab because this medicine was not suitable for them. The remaining 16 patients did not fall into either group. Arzerra was not compared with any other treatments in this study. The main measure of effectiveness was the number of patients who 'responded' to treatment. The response to treatment was assessed by looking at the patients' symptoms, the number of lymphocytes in their blood, results of blood and bone marrow tests and the size of their lymph nodes, liver and spleen.

Arzerra has also been studied in one main study involving 447 previously untreated patients who could not be treated with fludarabine-based therapy. Arzerra given together with chlorambucil was compared with chlorambucil alone. The main measure of effectiveness was progression-free survival (how long the patients lived without their disease getting worse).

What benefit has Arzerra shown during the studies?

In the study in patients whose disease had not responded to previous treatment, 49% of the patients whose previous treatment with both fludarabine and alemtuzumab had failed (47 out of 95) responded to treatment with Arzerra. The response rate was slightly lower in patients whose treatment with fludarabine had failed but who were not suitable for treatment with alemtuzumab (43%).

In previously untreated patients, Arzerra plus chlorambucil was effective at increasing progression-free survival, with patients living on average for 22.4 months without their disease getting worse, compared with 13.1 in patients given chlorambucil alone.

Arzerra

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What is the risk associated with Arzerra?

The most common side effects with Arzerra (seen in more than 1 patient in 10) are lower respiratory tract infection (infection of the lungs such as pneumonia), upper respiratory tract infection (colds), neutropenia (low levels of neutrophils, a type of white blood cell), anaemia (low red blood cell counts), nausea (feeling sick), pyrexia (fever) and rash. Arzerra treatment can also lead to infusion reactions, especially during the first infusion, which is why facilities for resuscitating patients should be readily available.

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

Why has Arzerra been approved?

The Committee decided that the medicine's benefits are greater than its risks and recommended that it be given marketing authorisation. The CHMP noted that Arzerra was shown to be effective at treating patients with CLL (both previously untreated patients and patients who had not responded to previous treatment with fludarabine and alemtuzumab). The Committee also noted that patients with CLL who had not responded to previous treatment have limited treatment options.

Arzerra was originally given 'conditional approval', because there was more evidence to come about the medicine. As the company has supplied the additional information necessary, the authorisation has been switched from conditional to full approval.

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

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

Other information about Arzerra:

The European Commission granted a conditional marketing authorisation valid throughout the European Union for Arzerra on 19 April 2010. This was switched to a full marketing authorisation on 24 April 2015.

The full EPAR for Arzerra 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 Arzerra, read the Package Leaflet (also part of the EPAR).

The summary of the opinion of the Committee for Orphan Medicinal Products for Arzerra can also be found on the Agency's website: ema.europa.eu/Find medicine/Human medicines/Rare disease designations.

This summary was last updated in 04-2016.

Arzerra

EMA/225378/2016