Iclusig

ponatinib

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

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

What is Iclusig and what is it used for?

Iclusig is a cancer medicine that contains the active substance ponatinib. It is used to treat adults with the following types of leukaemia (cancer of the white blood cells):

  • chronic myeloid leukaemia (CML) in its different stages known as chronic, accelerated and blast phases;
  • acute lymphoblastic leukaemia (ALL) in patients who are ‘Philadelphia-chromosome positive’ (Ph+). Ph+ means that some of the patient’s genes have rearranged themselves to form a special chromosome called the Philadelphia chromosome that leads to the development of leukaemia. The Philadelphia-chromosome is found in some ALL patients and is present in most patients with CML.

Iclusig is used in patients who cannot tolerate or do not respond to dasatinib or (for patients with CML) nilotinib, which are other cancer medicines of the same class, and in whom subsequent treatment with imatinib (a third such medicine) is not considered appropriate. It is also used in patients who have a genetic mutation called ‘T315I mutation’ which makes them resistant to treatment with imatinib, dasatinib or nilotinib.

Because the numbers of patients with CML and ALL are low, the diseases are considered ‘rare’, and Iclusig was designated an ‘orphan medicine’ (a medicine used in rare diseases) on 2 February 2010.

How is Iclusig used?

Iclusig can only be obtained with a prescription and treatment should be started by a doctor who is experienced in the diagnosis and treatment of leukaemia. Iclusig is available as tablets (15 mg and 45 mg). The recommended dose is 45 mg once per day. Treatment is continued until either the disease gets worse or until the patient cannot tolerate the medicine any longer. Iclusig can lead to clots or blockages in arteries and veins and patients should have the condition of their heart and circulation considered before starting and during treatment, and be treated appropriately for any problems. The dose may need to be reduced or interrupted if the patient experiences certain side effects; it should be interrupted immediately if a blockage develops in an artery or vein. For further information, see the package leaflet.

How does Iclusig work?

The active substance in Iclusig, ponatinib, belongs to a group of medicines called ‘tyrosine-kinase inhibitors’. These compounds act by blocking enzymes known as tyrosine kinases. Ponatinib acts by blocking a tyrosine kinase called Bcr-Abl. This enzyme is found in some receptors on the surface of leukaemia cells where it is involved in stimulating the cells to divide uncontrollably. By blocking Bcr-Abl, Iclusig helps to control the growth and spread of leukaemia cells.

What benefits of Iclusig have been shown in studies?

Iclusig has been investigated in one main study involving 449 patients with CML or Ph+ ALL and who were intolerant or resistant to treatment with dasatinib or nilotinib, or had the T315I mutation. In the study, Iclusig was not compared with another treatment. The response to treatment was assessed by measuring the proportion of patients who had a ‘major haematological response’ (when the number of white blood cells returns to normal or there is no evidence of leukaemia) or a ‘major cytogenetic response’ (when the proportion of white blood cells containing the Philadelphia chromosome falls to below 35%).

The results of the study showed that treatment with Iclusig led to clinically relevant responses in all groups of patients:

  • among the patients with CML in the chronic phase, around 54% (144 out of 267) had a major cytogenetic response;
  • among the patients with CML in the accelerated phase, around 58% (48 out of 83) had a major haematological response;
  • among the patients with CML in the blast phase, around 31% (19 out of 62) had a major haematological response;
  • among the patients with with Ph+ ALL, around 41% (13 out of 32) had a major haematological response.
What are the risks associated with Iclusig?

The most common serious side effects with Iclusig (which may affect more than 1 in 100 people) are pancreatitis (inflammation of the pancreas), abdominal pain (stomach ache), pyrexia (fever), anaemia (low red blood cell counts), febrile neutropenia (low white blood cell counts with fever), decreased blood levels of platelets (components that help the blood to clot) and neutrophils (a type of white blood cell), myocardial infarction (heart attack), diarrhoea, increased levels of lipase (an enzyme) and pancytopenia (low blood cell counts). Overall, the most common side effects (which may affect more than 2 in 10 people) are decreased levels of platelets, rash, dry skin and abdominal pain.

For the full list of all side effects reported with Iclusig, see the package leaflet.

Why is Iclusig approved?

The Agency’s Committee for Medicinal Products for Human Use (CHMP) decided that Iclusig’s benefits are greater than its risks and recommended that it be approved for use in the EU. The CHMP noted that Iclusig was shown to be an effective treatment for those patients with CML or Ph+ ALL who have limited treatment options. Regarding its safety, the side effects with Iclusig were largely similar to other tyrosine kinase inhibitors and mostly manageable with dose reduction or dose delay. The risk of problems (including heart attacks and strokes) resulting from blood clots or blockages in arteries or veins could be reduced by checking for and treating contributory conditions such as high blood pressure and raised cholesterol both before and during treatment.

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

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

Other information about Iclusig

The European Commission granted a marketing authorisation valid throughout the European Union for Iclusig on 1 July 2013.

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

Name Language First published Last updated
Iclusig : EPAR - Summary for the public BG = bălgarski 11/07/2013 15/01/2014
Iclusig : EPAR - Summary for the public ES = español 11/07/2013 15/01/2014
Iclusig : EPAR - Summary for the public CS = čeština 11/07/2013 15/01/2014
Iclusig : EPAR - Summary for the public DA = dansk 11/07/2013 15/01/2014
Iclusig : EPAR - Summary for the public DE = Deutsch 11/07/2013 15/01/2014
Iclusig : EPAR - Summary for the public ET = eesti keel 11/07/2013 15/01/2014
Iclusig : EPAR - Summary for the public EL = elliniká 11/07/2013 15/01/2014
Iclusig : EPAR - Summary for the public EN = English 11/07/2013 15/01/2014
Iclusig : EPAR - Summary for the public FR = français 11/07/2013 15/01/2014
Iclusig : EPAR - Summary for the public IT = italiano 11/07/2013 15/01/2014
Iclusig : EPAR - Summary for the public LV = latviešu valoda 11/07/2013 15/01/2014
Iclusig : EPAR - Summary for the public LT = lietuvių kalba 11/07/2013 15/01/2014
Iclusig : EPAR - Summary for the public HU = magyar 11/07/2013 15/01/2014
Iclusig : EPAR - Summary for the public MT = Malti 11/07/2013 15/01/2014
Iclusig : EPAR - Summary for the public NL = Nederlands 11/07/2013 15/01/2014
Iclusig : EPAR - Summary for the public PL = polski 11/07/2013 15/01/2014
Iclusig : EPAR - Summary for the public PT = português 11/07/2013 15/01/2014
Iclusig : EPAR - Summary for the public RO = română 11/07/2013 15/01/2014
Iclusig : EPAR - Summary for the public SK = slovenčina 11/07/2013 15/01/2014
Iclusig : EPAR - Summary for the public SL = slovenščina 11/07/2013 15/01/2014
Iclusig : EPAR - Summary for the public FI = suomi 11/07/2013 15/01/2014
Iclusig : EPAR - Summary for the public SV = svenska 11/07/2013 15/01/2014
Iclusig : EPAR - Summary for the public HR = Hrvatski 11/07/2013 15/01/2014

This EPAR was last updated on 26/08/2014 .

Authorisation details

Product details

Product details for Iclusig
NameIclusig
Agency product numberEMEA/H/C/002695
Active substance

ponatinib

International non-proprietary name (INN) or common name

ponatinib

Therapeutic area Leukemia, LymphoidLeukemia, Myeloid
Anatomical therapeutic chemical (ATC) code L01XE24
Additional monitoring

This medicine is under additional monitoring. This means that it is being monitored even more intensively than other medicines. For more information, see medicines under additional monitoring.

Treatment of rare diseases

This medicine has an "orphan designation" which means that it is used to treat life-threatening or chronically debilitating conditions that affect no more than five in 10,000 people in the European Union, or are medicines which, for economic reasons, would be unlikely to be developed without incentives.

Publication details

Publication details for Iclusig
Marketing-authorisation holder

Ariad Pharma Ltd

Revision4
Date of issue of marketing authorisation valid throughout the European Union01/07/2013

Contact address:

Ariad Pharma Ltd
Brooklands Business Park
Wellington Way
Weybridge
KT13 0TT
United Kingdom

Product information

Product information

22/05/2014  Iclusig -EMEA/H/C/002695 -II/0005/G

Name Language First published Last updated
Iclusig : EPAR - Product Information HR = Hrvatski 11/07/2013 26/08/2014
Iclusig : EPAR - Product Information HR = Hrvatski 11/07/2013 26/08/2014
Iclusig : EPAR - Product Information HR = Hrvatski 11/07/2013 26/08/2014
Iclusig : EPAR - Product Information HR = Hrvatski 11/07/2013 26/08/2014
Iclusig : EPAR - Product Information HR = Hrvatski 11/07/2013 26/08/2014
Iclusig : EPAR - Product Information HR = Hrvatski 11/07/2013 26/08/2014
Iclusig : EPAR - Product Information HR = Hrvatski 11/07/2013 26/08/2014
Iclusig : EPAR - Product Information HR = Hrvatski 11/07/2013 26/08/2014
Iclusig : EPAR - Product Information HR = Hrvatski 11/07/2013 26/08/2014
Iclusig : EPAR - Product Information HR = Hrvatski 11/07/2013 26/08/2014
Iclusig : EPAR - Product Information HR = Hrvatski 11/07/2013 26/08/2014
Iclusig : EPAR - Product Information HR = Hrvatski 11/07/2013 26/08/2014
Iclusig : EPAR - Product Information HR = Hrvatski 11/07/2013 26/08/2014
Iclusig : EPAR - Product Information HR = Hrvatski 11/07/2013 26/08/2014
Iclusig : EPAR - Product Information HR = Hrvatski 11/07/2013 26/08/2014
Iclusig : EPAR - Product Information HR = Hrvatski 11/07/2013 26/08/2014
Iclusig : EPAR - Product Information HR = Hrvatski 11/07/2013 26/08/2014
Iclusig : EPAR - Product Information HR = Hrvatski 11/07/2013 26/08/2014
Iclusig : EPAR - Product Information HR = Hrvatski 11/07/2013 26/08/2014
Iclusig : EPAR - Product Information HR = Hrvatski 11/07/2013 26/08/2014
Iclusig : EPAR - Product Information HR = Hrvatski 11/07/2013 26/08/2014
Iclusig : EPAR - Product Information HR = Hrvatski 11/07/2013 26/08/2014
Iclusig : EPAR - Product Information HR = Hrvatski 11/07/2013 26/08/2014
Iclusig : EPAR - Product Information HR = Hrvatski 11/07/2013 26/08/2014
Iclusig : EPAR - Product Information HR = Hrvatski 11/07/2013 26/08/2014

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.


Name Language First published Last updated
Iclusig : EPAR - All Authorised presentations HR = Hrvatski 11/07/2013  
Iclusig : EPAR - All Authorised presentations HR = Hrvatski 11/07/2013  
Iclusig : EPAR - All Authorised presentations HR = Hrvatski 11/07/2013  
Iclusig : EPAR - All Authorised presentations HR = Hrvatski 11/07/2013  
Iclusig : EPAR - All Authorised presentations HR = Hrvatski 11/07/2013  
Iclusig : EPAR - All Authorised presentations HR = Hrvatski 11/07/2013  
Iclusig : EPAR - All Authorised presentations HR = Hrvatski 11/07/2013  
Iclusig : EPAR - All Authorised presentations HR = Hrvatski 11/07/2013  
Iclusig : EPAR - All Authorised presentations HR = Hrvatski 11/07/2013  
Iclusig : EPAR - All Authorised presentations HR = Hrvatski 11/07/2013  
Iclusig : EPAR - All Authorised presentations HR = Hrvatski 11/07/2013  
Iclusig : EPAR - All Authorised presentations HR = Hrvatski 11/07/2013  
Iclusig : EPAR - All Authorised presentations HR = Hrvatski 11/07/2013  
Iclusig : EPAR - All Authorised presentations HR = Hrvatski 11/07/2013  
Iclusig : EPAR - All Authorised presentations HR = Hrvatski 11/07/2013  
Iclusig : EPAR - All Authorised presentations HR = Hrvatski 11/07/2013  
Iclusig : EPAR - All Authorised presentations HR = Hrvatski 11/07/2013  
Iclusig : EPAR - All Authorised presentations HR = Hrvatski 11/07/2013  
Iclusig : EPAR - All Authorised presentations HR = Hrvatski 11/07/2013  
Iclusig : EPAR - All Authorised presentations HR = Hrvatski 11/07/2013  
Iclusig : EPAR - All Authorised presentations HR = Hrvatski 11/07/2013  
Iclusig : EPAR - All Authorised presentations HR = Hrvatski 11/07/2013  
Iclusig : EPAR - All Authorised presentations HR = Hrvatski 11/07/2013  
Iclusig : EPAR - All Authorised presentations HR = Hrvatski 11/07/2013  

Pharmacotherapeutic group

Antineoplastic agent, protein

Therapeutic indication

Iclusig is indicated in adult patients with:

  • chronic-phase, accelerated-phase or blast-phase chronic myeloid leukaemia (CML) who are resistant to dasatinib or nilotinib, who are intolerant to dasatinib or nilotinib and for whom subsequent treatment with imatinib is not clinically appropriate, or who have the T315I mutation;
  • Philadelphia-chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) who are resistant to dasatinib, who are intolerant to dasatinib and for whom subsequent treatment with imatinib is not clinically appropriate, or who have the T315I mutation.

Assessment History

Changes since initial authorisation of medicine

Name Language First published Last updated
Iclusig : EPAR - Procedural steps taken and scientific information after authorisation HR = Hrvatski 22/08/2013 26/08/2014

Initial marketing-authorisation documents

Name Language First published Last updated
Iclusig : EPAR - Public assessment report HR = Hrvatski 11/07/2013  
CHMP summary of positive opinion for Iclusig HR = Hrvatski 22/03/2013