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Further review of Iclusig started

The European Medicines Agency has started an in-depth review of the benefits and risks of the leukaemia medicine Iclusig, particularly the risk of blood clots or blockages in the arteries or veins that is associated with the medicine.

In November 2013, the European Medicines Agency reviewed updated clinical trial data with Iclusig indicating that cases of blood clots and blockages in the arteries or veins were occurring at a higher rate than was observed at the time of the medicine’s initial authorisation. The Agency therefore recommended a number of measures to help minimise this risk. These included a warning against use in patients who have had a heart attack or stroke in the past, and a recommendation that the cardiovascular risks (affecting the heart and blood vessels) of all patients be assessed and measures be taken to reduce such risks before and during treatment with Iclusig. Treatment with Iclusig should be stopped immediately in any patient with signs of a blockage in the arteries or veins.

However, a number of issues required further investigation, including a better understanding of the nature, frequency and severity of events obstructing the arteries or veins, the potential mechanism through which the medicine leads to these side effects and whether there is a need to revise the dosing recommendation of Iclusig. Therefore, the European Commission considered that a further in-depth review of relevant data was necessary.

The Agency will now carry out this review to assess the need for further changes to how the medicine is used.

More about the medicine

Iclusig is an anticancer 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);
  • acute lymphoblastic leukaemia (ALL) in patients who are ‘Philadelphia-chromosome positive’ (Ph+).

Iclusig is used in patients who cannot tolerate or do not respond to dasatinib or nilotinib (other anticancer medicines) and for whom subsequent treatment with imatinib 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.

The active substance in Iclusig, ponatinib, belongs to a group of medicines called ‘tyrosine-kinase inhibitors’. Ponatinib works by blocking a tyrosine kinase called Bcr-Abl, which 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.

Iclusig was authorised as an orphan medicine (a medicine used in rare diseases) in the EU in July 2013.

More about the procedure

The review of Iclusig was triggered on 27 November 2013 at the request of the European Commission, under Article 20 of Regulation (EC) No 726/2004.

The review will be carried out by the Pharmacovigilance Risk Assessment Committee (PRAC), the Committee responsible for the evaluation of safety issues for human medicines, which will make a set of recommendations. The PRAC recommendation will then be forwarded to the Committee for Medicinal Products for Human Use (CHMP), responsible for all questions concerning medicines for human use, which will adopt a final opinion.

The CHMP opinion will then be sent to the European Commission for a legally binding decision, valid throughout the EU.

Name Language First published Last updated
Iclusig Article-20 procedure - Review started (English only) 06/12/2013  

Key facts

About this medicine

Approved nameIclusig
International non-proprietary name (INN) or common name


Associated names

About this procedure

Current statusUnder evaluation
Reference numberEMEA/H/C/2695/A20/0003
TypeArticle 20 procedures

This type of procedure is triggered for medicines that have been authorised via the centralised procedure in case of manufacturing or safety issues.

Decision making modelPRAC-CHMP-EC
Authorisation modelCentrally authorised product(s)

Key dates and outcomes

Procedure start date05/12/2013

All documents

Procedure started

Name Language First published Last updated
Iclusig Article-20 procedure - Review started EN = English 06/12/2013  
Iclusig Article-20 procedure - Timetable for the procedure EN = English 06/12/2013 11/07/2014
Iclusig Article-20 procedure - PRAC list of questions EN = English 06/12/2013  
Iclusig Article-20 procedure - Notification EN = English 06/12/2013  

Document description:

  • Annex I - List of the medicines affected by the referral
  • Annex II - Scientific conclusions of the Committee for Medicinal Products for Human Use (CHMP) or Coordination Group for Mutual Recognition and Decentralised Procedures - Human (CMDh)
  • Annex III - Changes to the summary of product characteristics, labelling or package leaflet - available when the CHMP or CMDh recommends changes to the product information. Also includes conditions for lifting of suspensions, if applicable
  • Annex IV - Conditions of the marketing authorisation - available when the CHMP or CMDh recommends other measures to be taken for the marketing authorisation such as safety measures or additional studies
  • Notification - A letter from a Member State, the European Commission or a marketing-authorisation holder requesting the initiation of a referral procedure
  • Rationale for triggering - Background provided by the party triggering the referral explaining the issues leading to the initiation of the procedure
  • PRAC list of questions - Questions agreed by the PRAC requesting further information to evaluate the issues identified
  • PRAC timetable - Timeframe agreed by the PRAC to receive information, assess the issues and adopt a recommendation
  • PRAC / CHMP / CMDh assessment report - The assessment and conclusions of the PRAC and CHMP or CMDh on the issues investigated

Current status:
Under evaluation

More information on Iclusig