Alvesco - referral

Current status

European Commission final decision

Overview

Alvesco and associated names, 40 ug, 80 ug and 160 ug pressurised inhalation, solution is a glucocorticoid used to treat obstructive airway disease. The product contains ciclesonide which is delivered by a pressurized metered dose inhaler containing ethanolic hydrofluoroalkane-134A as a propellant.

Altana Pharma AG submitted applications for mutual recognition of Alvesco and associated names, 40ug, 80 ug and 160 ug pressurised inhalation, solution on the basis of the marketing authorisation granted by United Kingdom on 14 April 2004. The Mutual Recognition Procedure started on 2 May 2007. The Reference Member State was United Kingdom and the Concerned Member States were:
First wave: Belgium, Czech Republic, Denmark, Estonia, Finland, Germany, Greece, Hungary, Iceland, Ireland, Latvia, Lithuania, Luxembourg, The Netherlands, Norway, Poland, Slovak Republic, Slovenia and Sweden
Repeat use: Austria, Bulgaria, Cyprus, Spain, France, Italy, Malta and Portugal

These Member States and the applicant / MAH were not able to reach an agreement in respect of the Mutual Recognition of the Marketing Authorisation granted by the Reference Member State. The United Kingdom referred the reasons of disagreement to the EMEA on 25 October 2007.

Significant difference have been identified with regard to the currently approved posology for the control of exacerbations in severe asthma, and the need for a study comparing 160 ug, 320 ug and 640 ug/daily to demonstrate a reduction in the frequency of exacerbations in patients with severe asthma at the higher doses.

The data supporting this application, as interpreted according with the CHMP guidance, did not support authorization of regular daily doses in excess of 160 μg in the treatment populations, and this was considered to be of serious public health concern.

The arbitration procedure started on 15 November 2007 with the adoption of a list of questions. The Rapporteur was Dr Ian Hudson and Co-Rapporteur was Dr Pierre Demolis. The Marketing Authorisation Holder provided written explanations on 16 January 2008.

During their March 2008 meeting, the CHMP, in the light of the overall data submitted and the scientific discussion within the Committee, was of the opinion that the benefit/risk ratio is favourable for Alvesco and associated names, that the objections raised by France should not prevent the granting of a Marketing Authorisation and that the Summary of Product Characteristics, labelling and package leaflet of the Reference Member State should be amended. A positive opinion was adopted by consensus on 19 March 2008.

In particular, the proposed wording for Section 4.2 at the end of CMDh procedure was amended to reflect
that in severe asthmatics, a 12 week study provided by the applicant/MAH has shown that a dose of 640μg/d
(given 320μg/d twice daily) demonstrated a reduction in the frequency of exacerbations but without an
improvement in lung function. The applicant/MAH also accepted an updated wording for Section 5.1, which
includes more detail on Study M1-140, at the end of the CMDh procedure, and a fully updated Package
Leaflet.

Additionally, the applicant/MAH was requested to commit to obtaining scientific advice in relation to exploring a suitable study design, and executing such study(ies) to provide further information on the use of the higher dose of Alvesco in the control of severe asthma. In light of this, the applicant/MAH proposed a study which would resolve the outstanding question on the long term use of 320 μg and 640 μg daily.

The list of the product names concerned is given in Annex I. The scientific conclusions are provided in Annex II, together with the Summary of Product Characteristics in Annex III.

The final opinion was converted into a Decision by the European Commission on 11 July 2008.

Opinion following an Article 29(4) referral for Alvesco and associated names International Non-Proprietary Name (INN): ciclesonide: Background information

Adopted Reference Number: EMEA/CHMP/151554/2008

Key facts

About this medicine

• Approved name:
  Alvesco
• International non-proprietary name (INN) or common name:
  ciclesonide

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  CHMP/151554/08
• Type:
  Article 29(4) referrals

  This type of referral is triggered when there is a disagreement between Member States regarding a marketing authorisation application being evaluated in a mutual-recognition or decentralised procedure, on the grounds of a potential serious risk to public health.

Key dates and outcomes

• CHMP opinion date:
  20/03/2008
• EC decision date:
  11/07/2008

All documents

Alvesco - Article 29 referral - Annex I, II, III

Adopted

Opinion following an Article 29(4) referral for Alvesco and associated names International Non-Proprietary Name (INN): ciclesonide: Background information

Adopted Reference Number: EMEA/CHMP/151554/2008

Description of documents published

Please note that some of the listed documents apply only to certain procedures.

• Overview - lay-language summary of the stage of the procedure
• Notification – a letter from a Member State, the European Commission or the marketing authorisation holder requesting the initiation of the procedure
• Scientific background – further background information from the triggering Member State on the issues leading to the initiation of the procedure (if applicable)
• List of questions – questions agreed by the Committee requesting further information from the marketing authorisation holder(s) / applicant(s) to evaluate the issues identified
• Timetable for the procedure – agreed timeframe to respond to the list of questions, to assess the issues and to adopt a conclusion
• List of medicines concerned by the procedure – medicine(s) / active substance(s) concerned, and marketing authorisation holder(s) / applicant(s)
• List of questions to be addressed by the stakeholders – call for data to be submitted by stakeholders (e.g. healthcare professionals, patient organisations, individual patients) (if applicable)
• Stakeholder submission form – form to be used by stakeholders to submit data (if applicable)
• Scientific conclusions – scientific conclusions of the PRAC and/or CHMP and/or CMDh
• Assessment report – PRAC or CHMP assessment and conclusions on the issues investigated, including divergent positions (if applicable)
• Divergent positions – divergent positions of the CHMP or CMDh members for pharmacovigilance procedures (if applicable)
• Changes to the summary of product characteristics, labelling and package leaflet (amended sections or fully revised version) (if applicable)
• Condition(s) to the marketing authorisation(s) – condition(s) for the safe and effective use of the medicine(s) (if applicable)
• Condition for lifting the suspension – condition to be fulfilled for the suspension of the marketing authorisation(s) to be lifted (if applicable)
• Timetable for implementation of CMDh position – agreed timeframe to submit and finalise the variation(s) implementing the outcome of the procedure (if applicable)

Note that older documents may have different titles.