- Procedure started
- Under evaluation
- CHMP opinion
- European Commission final decision
Sortis and associated names contain atorvastatin, a HMG-CoA-reductase inhibitor (known as statin), which inhibits the synthesis of cholesterol. It is registered in the EU since 1996 through Mutual Recognition Procedure and national procedures. Atorvastatin is currently indicated as an adjunct to diet for reduction of elevated total cholesterol, LDL-cholesterol, apolipoprotein B, and triglycerides in patients with primary hypercholesterolaemia including familial hypercholesterolaemia (heterozygous variant) or combined (mixed) hyperlipidaemia (Corresponding to Types IIa and IIb of the Fredrickson classification) when response to diet and other nonpharmacological measures is inadequate.
Atorvastatin is also indicated to reduce total-C and LDL-C in patients with homozygous familial hypercholesterolaemia as an adjunct to other lipid-lowering treatments (e.g. LDL apheresis) or if such treatments are unavailable.
This Referral procedure relates to a request for Arbritation concerning a type II variation for a new indication in the "Prevention of cardiovascular events in patients estimated to have a high risk for a first cardiovascular event, as an adjunct to correction of other risk factors". At the end of the MRP procedure there was a discrepancy between different Member States regarding the wording of the indication that adequately reflects the clinical data submitted by the company, and an official referral for arbitration according to Article 6(12) of Commission Regulation EC No 1084/2003, as amended, was notified by Spain to the CHMP on 1.12.2005.
The arbitration procedure was discussed and initiated by the CHMP at its plenary meeting in December 2005, and a Rapporteur (Dr Eric Abadie) and Co-Rapporteur (Dr Bengt Ljungberg) were appointed. The questions identified pertained to:
- the lack of a significant effect in favour of atorvastatin for the composite primary endpoint and several secondary endpoints in the female subgroup,
- the exclusion of non-diabetic patients at high cardiovascular risk from the proposed indication,
- the higher cardioprotective effect of atorvastatin when used in combination with particular antihipertensive therapies
- the extent to which the claimed therapeutic indication could be applied to atorvastatin doses other than those tested in the pivotal trials
The company responded to these points on 19 January 2006.
Based on the evaluation of the currently available data and the (Co-)Rapporteurs' assessment reports, the CHMP adopted an opinion on 23 March 2006 recommending the variation of the Marketing Authorisations for the addition of the following new indication:
"Prevention of cardiovascular events in patients estimated to have a high risk for a first cardiovascular event (see section 5.1), as an adjunct to correction of other risk factors."
The list of product names concerned is given in the Annex I. The scientific conclusions are provided in the Annex II, together with the amended Summary of Product Characteristics in the Annex III.
The final opinion was converted into a Decision by the European Commission on 22 May 2006.
|International non-proprietary name (INN) or common name||
Article 6(12) referrals (prior to January 2010)
This type of referral was triggered for a medicine that had been authorised by mutual recognition or via the decentralised procedure when there was disagreement between Member States on a variation (type II). This referral has been replaced by Article 13 referrals.
European Commission final decision
|EC decision date||
Opinion following an Article 6(12) referral for Sortis International Non-Proprietary Name (INN): atorvastatin: Background information (PDF/28.79 KB)Adopted
First published: 22/05/2006
Last updated: 22/05/2006
Sortis - Article 6 (12) referral - Annex I, II, III (PDF/598.36 KB)Adopted
First published: 09/12/2006
Last updated: 09/12/2006
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.