Tysabri

  • Procedure started
  • Under evaluation
  • PRAC recommendation
  • CHMP opinion
  • European Commission final decision
Current status:
European Commission final decision

Overview

EMA confirms recommendations to minimise risk of brain infection PML with Tysabri

More frequent MRI scans should be considered for patients at higher risk

On 25 February 2016, EMA completed its review of the known risk of progressive multifocal leukoencephalopathy (PML) with the multiple sclerosis medicine Tysabri (natalizumab), and confirmed initial recommendations1 aimed at minimising this risk.

PML is a rare brain infection caused by John Cunningham (JC) virus. This virus is very common in the general population and is normally harmless; however, it can lead to PML in persons whose immune system is weakened. The most common symptoms of PML are progressive weakness, speech and communication difficulties, vision changes, and sometimes changes in mood or behaviour. PML is a very serious condition that may result in severe disability or death.

Recent studies suggest that early detection and treatment of PML when the disease is asymptomatic (is still in the initial stages and shows no symptoms) may improve patients' outcomes. Asymptomatic cases of PML can be detected on MRI scans, and experts in the field of MRI and multiple sclerosis agree that simplified MRI protocols (which allow for shorter procedures, and also limit the burden for patients undergoing the scans) permit the identification of PML lesions. All patients taking Tysabri should undergo full MRI scans at least once a year, but on the basis of the new data EMA recommended that for patients at higher risk of PML more frequent MRI scans (e.g. every 3 to 6 months) performed using simplified protocols should be considered. If lesions suggestive of PML are discovered, the MRI protocol should be extended to include 'contrast-enhanced T1-weighted MRI', and testing the spinal fluid for the presence of JC virus should be considered.

New data from large clinical studies also suggest that, in patients who have not been treated with immunosuppressants (medicines that reduce the activity of the immune system) before starting Tysabri, the blood level of antibodies against JC virus ('antibody index') relates to the level of risk for PML. In light of the new evidence, patients are considered at higher risk of developing PML if they:

  • have tested positive for JC virus, and
  • have been treated with Tysabri for more than 2 years, and
  • either have used an immunosuppressant before starting Tysabri, or have not used immunosuppressants and have a high JC virus antibody index.

In these patients, treatment with Tysabri should only be continued if benefits outweigh the risks.

If PML is suspected at any time, treatment with Tysabri must be stopped until PML has been excluded.

EMA's recommendations are based on an initial review by its Pharmacovigilance Risk Assessment Committee (PRAC). The PRAC recommendations were sent to the Committee for Medicinal Products for Human Use (CHMP), which confirmed them and adopted its final opinion. The CHMP's opinion was then sent to the European Commission, which issued a legally-binding decision valid throughout the EU.


1PRAC recommendations issued on 11 February 2016.

Key facts

About this medicine
Approved name
Tysabri
International non-proprietary name (INN) or common name
natalizumab
Associated names
Tysabri
Class
-
About this procedure
Current status
European Commission final decision
Reference number
EMEA/H/A-20/1416/C/000603/0083
Type
Article 20 procedures

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

Decision making model
PRAC-CHMP-EC
Authorisation model
Centrally authorised product(s)
Key dates and outcomes
Procedure start date
07/05/2015
PRAC recommendation date
11/02/2016
CHMP opinion/CMDh position date
25/02/2016
EC decision date
25/04/2016
Outcome
Risk minimisation measures

All documents

Procedure started

Recommendation provided by Pharmacovigilance Risk Assessment Committee

Opinion provided by Committee for Medicinal Products for Human Use

European Commission final decision

  • List item

    Tysabri Article-20 procedure - EMA confirms recommendations to minimise risk of brain infection PML with Tysabri (PDF/112.01 KB)


    First published: 26/02/2016
    Last updated: 12/05/2016
    EMA/137488/2016

  • List item

    Tysabri Article-20 procedure - Annex IV (PDF/72.27 KB)


    First published: 12/05/2016
    Last updated: 12/05/2016

  • List item

    Tysabri Article-20 procedure - Annex I-III (PDF/328.48 KB)


    First published: 26/02/2016
    Last updated: 12/05/2016

  • List item

    Tysabri Article-20 procedure - EMA confirms recommendations to minimise risk of brain infection PML with Tysabri (PDF/112.01 KB)


    First published: 26/02/2016
    Last updated: 12/05/2016
    EMA/137488/2016

  • Document description

    • Annex I - List of the medicines affected by the referral
    • Annex II - Scientific conclusions of the CHMP or 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 or CMDh assessment report - The assessment and conclusions of the PRAC and CHMP or CMDh on the issues investigated

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