Didanosine - referral

Current status

European Commission final decision

Overview

On 19 September 2013, the European Medicines Agency completed an arbitration procedure following a disagreement among Member States of the European Union (EU) regarding the authorisation of the medicine Didanosine. The Agency's Committee for Medicinal Products for Human Use (CHMP) concluded that the benefits of Didanosine outweigh its risks, and the marketing authorisation can be granted in the United Kingdom and in the following Member States of the EU: France, Germany, Italy, the Netherlands, Portugal, Romania and Spain.

What is Didanosine?

Didanosine is an antiviral medicine used in combination with other medicines to treat patients infected with human immunodeficiency virus type 1 (HIV-1), a virus that causes acquired immune deficiency syndrome (AIDS).

Didanosine belongs to a class of medicines called nucleoside analogues or nucleoside reverse-transcriptase inhibitors (NRTIs). It blocks the activity of reverse transcriptase, an enzyme produced by HIV-1 that allows it to make more viruses in the cells it has infected. By blocking this enzyme, didanosine, taken in combination with other antiviral medicines, reduces the amount of HIV in the blood and keeps it at a low level. Didanosine does not cure HIV infection or AIDS, but it may delay the damage to the immune system and the development of infections and diseases associated with AIDS.

Didanosine is a hybrid medicine which means that it is similar to a 'reference medicine' already authorised in the EU called Videx EC. It is available as gastroresistant tablets. 'Gastroresistant' means that the tablet's contents pass through the stomach without being broken down until they reach the intestine. This prevents the active substance from being destroyed by the acid in the stomach.

Why was Didanosine reviewed?

Aurobindo Pharma (Malta) Limited submitted Didanosine to the UK medicines regulatory agency for a decentralised procedure. This is a procedure where one Member State (the 'reference Member State', in this instance the UK) assesses a medicine with a view to granting a marketing authorisation that will be valid in this country as well as in other Member States (the 'concerned Member States', in this instance France, Germany, Italy, Netherlands, Portugal, Romania and Spain).

However, the Member States were not able to reach an agreement and the UK medicines regulatory agency referred the matter to the CHMP for arbitration on 4 March 2013.

The grounds for the referral were objections raised by France and the Netherlands that the bioequivalence study carried out under fed conditions did not show that Didanosine was bioequivalent to its reference medicine, Videx EC. Although the presence of food in the stomach lowers the amount of active substance that can be absorbed and these medicines should therefore be taken on an empty stomach, as Didanosine is a gastroresistant preparation, bioequivalence in fed conditions must be shown to grant the marketing authorisation. Two medicines are bioequivalent if they produce the same levels of the active substance in the body.

What are the conclusions of the CHMP?

Based on evaluation of the currently available data and the scientific discussion within the Committee, the CHMP concluded that bioequivalence to the reference medicine has been shown when taken on an empty stomach, and under fed conditions when considering the overall exposure to the active substance (a measure known as area under the curve, AUC). Although the Committee noted that the maximum concentrations of active substance in the blood when taken with food were somewhat higher after Didanosine than after the reference medicine, it considered that the difference was not clinically relevant since the medicine should be taken on an empty stomach, which produces much higher concentrations, and these small variations in the concentration of the active substance in the blood would therefore not increase the risks. The CHMP therefore concluded that the benefits of Didanosine outweigh its risks and recommended that the marketing authorisation be granted in the concerned Member States.

The European Commission issued a decision on 20 November 2013.

Questions and answers on Didanosine and associated names (didanosine, gastro-resistant capsules, 200, 250 and 400 mg)

Reference Number: EMA/562334/2013 Rev.1

Key facts

About this medicine

• Approved name:
  Didanosine
• International non-proprietary name (INN) or common name:
  didanosine
• Class:
  -

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/H/A-29/1367
• 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:
  19/09/2013
• EC decision date:
  20/11/2013

All documents

Opinion provided by Committee for Medicinal Products for human Use

Questions and answers on Didanosine and associated names (didanosine, gastro-resistant capsules, 200, 250 and 400 mg)

Reference Number: EMA/562334/2013 Rev.1

European Commission final decision

Didanosine Article-29 referral - Annex I

Didanosine Article-29 referral - Annex II

Didanosine Article-29 referral - Annex III

Didanosine Article-29 referral - Assessment report

Adopted Reference Number: EMA/686289/2013

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.