Jakavi

ruxolitinib

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

What is Jakavi?

Jakavi is a medicine that contains the active substance ruxolitinib. It is available as tablets (5, 15 and 20 mg).

What is Jakavi used for?

Jakavi is used to treat adults with myelofibrosis who have splenomegaly (enlarged spleen) or symptoms related to the disease such as fever, night sweats, bone pain and weight loss.

Myelofibrosis is a disease in which the bone marrow becomes very dense and rigid and produces abnormal, immature blood cells. Jakavi can be used in three types of the disease: primary myelofibrosis (also known as chronic idiopathic myelofibrosis, where the cause is unknown), post-polycythaemia-vera myelofibrosis (where the disease is linked to an overproduction of red blood cells) and post-essential-thrombocythaemia myelofibrosis (where the disease is linked to an overproduction of platelets, components that help the blood to clot).

Because the number of patients with these diseases is low, they are considered ‘rare’, and Jakavi was designated an ‘orphan medicine’ (a medicine used in rare diseases) for chronic idiopathic myelofibrosis on 7 November 2008 and for myelofibrosis secondary to polycythaemia vera or essential thrombocythaemia on 3 April 2009.

The medicine can only be obtained with a prescription.

How is Jakavi used?

Treatment with Jakavi should only be started by a doctor who is experienced in treating patients with anticancer medicines. The patient’s complete blood cell count must be taken before starting treatment and monitored during treatment. The recommended starting dose is 5 mg, 15 mg or 20 mg twice a day depending on the platelet count, which can be increased by 5 mg if the treatment is not considered effective enough. A lower dose should be used in patients with reduced platelet counts, reduced liver function or severely reduced kidney function, and in patients taking certain other medicines. Treatment should be stopped if the patient’s blood levels of platelets or neutrophils (a type of white blood cell) fall below certain thresholds, or if no improvement in spleen size or symptoms is seen after six months.

How does Jakavi work?

The active substance in Jakavi, ruxolitinib, works by blocking a group of enzymes known as Janus kinases (JAKs), which are involved in the production and growth of blood cells. In myelofibrosis, they are overactivated, leading to the production of many abnormal, immature blood cells. These immature blood cells migrate to organs including the spleen, causing them to become enlarged. By blocking the enzymes, Jakavi reduces the production of abnormal blood cells, thereby reducing the enlargement of the spleen and symptoms of the disease.

How has Jakavi been studied?

The effects of Jakavi were first tested in experimental models before being studied in humans.

Jakavi was investigated in two main studies involving 528 patients with myelofibrosis. The first study compared Jakavi with placebo (a dummy treatment). The second study compared Jakavi with the best available treatment, which included different types of medicines such as anticancer agents, hormones and immunosuppressants. The main measure of effectiveness was the proportion of patients whose spleen had reduced in size by at least 35%, measured after six months in the first study and after one year in the second study.

What benefit has Jakavi shown during the studies?

Jakavi was more effective than placebo and the best available treatment at reducing the size of the spleen. In the first study, the target reduction in spleen size was achieved in 42% of patients treated with Jakavi (65 out of 155) compared with less than 1% of patients given placebo (1 out of 153). In the second study, the target reduction in spleen size was achieved in 29% of patients treated with Jakavi (41 out of 144) compared with 0% of patients receiving the best available treatment (0 out of 72).

What is the risk associated with Jakavi?

The most common side effects with Jakavi (seen in more than 1 patient in 10) are thrombocytopenia (low blood platelet counts), anaemia (low red-blood-cell counts), neutropenia (low levels of neutrophils), urinary-tract infections (infection of the structures that carry urine), bleeding, bruising, weight gain, hypercholesterolaemia (high blood cholesterol levels), dizziness, headache and raised liver enzyme levels. For the full list of all side effects reported with Jakavi, see the package leaflet.

Jakavi must not be used in people who are hypersensitive (allergic) to ruxolitinib or any of the other ingredients. It must not be used in women who are pregnant or breast-feeding.

Why has Jakavi been approved?

The CHMP considered that the reduction in spleen size and symptoms related to myelofibrosis seen in patients taking Jakavi is clinically important. The Committee noted that the quality of life of patients treated with Jakavi was improved but that the medicine’s effects had still to be evaluated in terms of extending the life of patients or delaying the progress of the disease or the onset of leukaemia. With regard to safety, the Committee considered that the risk of infections is acceptable but should be monitored further, while other known risks, such as bleeding or a reduction in blood cell counts, can be appropriately managed. The CHMP therefore decided that Jakavi’s benefits are greater than its risks and recommended that it be given marketing authorisation.

What information is still awaited for Jakavi?

Each year, the company that makes Jakavi will provide further study data on the effects of Jakavi in terms of how long patients live and how long they live without their disease getting worse or developing leukaemia.

Other information about Jakavi

The European Commission granted a marketing authorisation valid throughout the European Union for Jakavi on 23 August 2012.

For more information about treatment with Jakavi, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This EPAR was last updated on 10/04/2013 .

More detail is available in the summary of product characteristics

Product details

Publication details

Product information

20/02/2013  Jakavi -EMEA/H/C/002464 -IB/002G

Contents

• Annex I - Summary of product characteristics
• Annex IIA - Manufacturing-authorisation holder responsible for batch release
• Annex IIB - Conditions of the marketing authorisation
• Annex IIIA - Labelling
• Annex IIIB - Package leaflet

Please note that the size of the above document can exceed 50 pages.

You are therefore advised to be selective about which sections or pages you wish to print.

Pharmacotherapeutic group

Antineplastic agents

Therapeutic indication

Treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis (also known as chronic idiopathic myelofibrosis), post-polycythaemia-vera myelofibrosis or post-essential-thrombocythaemia myelofibrosis.

Changes since initial authorisation of medicine

Initial marketing-authorisation documents