Daruph and Anafezyn - referral

Current status

European Commission final decision

Overview

On 19 May 2022, the European Medicines Agency completed a review of Daruph/Anafezyn¹ following a disagreement among EU Member States regarding its authorisation. The Agency concluded that the benefits of Daruph/Anafezyn outweigh its risks, and that the marketing authorisation should be granted in Sweden and in the Member States of the EU where the company applied for a marketing authorisation (France, Germany, Hungary, Ireland, Italy, Poland, Portugal, Romania and Slovakia).

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¹These medicines are identical and were submitted as part of a so called ‘duplicate application’. They are referred to as Daruph/Anafezyn in this document. Daruph/Anafezyn was also to be available in the EU under the trade name Dasatinib Zentiva.

What is Daruph / Anafezyn?

Daruph/Anafezyn is a cancer medicine to be used in adults and children to treat chronic myeloid leukaemia (CML) and acute lymphoblastic leukaemia (ALL). Leukaemia is a cancer of the white blood cells (called granulocytes in the case of CML and lymphocytes in ALL) where the cells grow out of control. In some cases, Daruph/Anafezyn is for use in patients whose cancer cells are ‘Philadelphia chromosome positive’ (when the patient’s genes have rearranged themselves to form a special chromosome called the Philadelphia chromosome).

Daruph/Anafezyn is to be available as tablets to be taken by mouth and contains the active substance dasatinib, which belongs to the class of protein kinase inhibitors.

Daruph/Anafezyn was developed as a hybrid medicine. This means that it is similar to a reference medicine called Sprycel which is already authorised in the EU and contains the same active substance. However, the form of the active substance in Daruph/Anafezyn (dasatinib anhydrous) is different to that in Sprycel (dasatinib monohydrate) and is intended to allow the use of a lower dose of dasatinib to achieve the same effect. It is also intended to allow the use of proton pump inhibitors (PPIs) or histamine 2 (H2) antagonists (medicines used to reduce stomach acid) while taking Daruph/Anafezyn.

Why was Daruph / Anafezyn reviewed?

The company intending to market Daruph/Anafezyn, Zentiva k.s., submitted a marketing authorisation application to the Swedish medicines regulatory agency for a decentralised procedure. This is a procedure where one Member State (the ‘reference Member State’, in this instance Sweden) 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 where the company has applied for a marketing authorisation (the ‘concerned Member States’, in this instance France, Germany, Hungary, Ireland, Italy, Poland, Portugal, Romania and Slovakia).

However, the Member States were not able to reach an agreement and the Swedish medicines regulatory agency referred the matter to EMA for arbitration on 23 December 2021.

The grounds for the referral were three concerns raised by Germany, Italy and Slovakia. The first concern was that, according to current guidance for dasatinib medicines, the data submitted were not sufficient to show that Daruph/Anafezyn has the same effect and safety profile as the reference medicine Sprycel. There were also concerns about a risk of medication error if switching from another dasatinib medicine to Daruph/Anafezyn. Although not recommended, this could lead to lower effectiveness or to side effects due to the difference in the strengths of Daruph/Anafezyn compared with the available strengths of authorised dasatinib medicines. The final concern related to the company’s proposal to change the warning in the product information to allow the use of PPIs and H2 antagonists when taking Daruph/Anafezyn, while such use is not recommended for Sprycel as it may reduce Sprycel’s effectiveness due to a lower level of the medicine available in the body.

What is the outcome of the review?

Based on evaluation of the currently available data, EMA concluded that Daruph/Anafezyn has a similar effect as the reference medicine Sprycel. The Agency also considered that the risk minimisation measures proposed by the company were sufficient to address the potential risk of medication error. Finally, EMA considered that there was sufficient evidence to allow the use of PPIs and H2 antagonists while taking Daruph/Anafezyn, since the form of the active substance in this medicine means its activity is less sensitive to changes in stomach acidity than that of Sprycel.

The Agency therefore concluded that the benefits of Daruph/Anafezyn outweigh its risks and recommended that the marketing authorisation for Daruph/Anafezyn should be granted in the concerned Member States.

More about the procedure

The review of Daruph/Anafezyn was initiated on 27 January 2022 at the request of the Sweden medicines regulatory authority under Article 29(4) of Directive 2001/83/EC.

The review was carried out by EMA’s Committee for Medicinal Products for Human Use (CHMP), responsible for questions concerning medicines for human use.

A European Commission decision valid throughout the EU will be issued in due course.

Daruph and Anafezyn Article 29(4) referral - EMA recommends authorisation of Daruph / Anafezyn (dasatinib anhydrous) in the EU

Reference Number: EMA/662970/2022

Key facts

About this medicine

• Approved name:
  Daruph and Anafezyn
• International non-proprietary name (INN) or common name:
  dasatinib (anhydrous)

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/H/A-29(4)/1516
• 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.

• Authorisation model:
  Nationally authorised product(s)
• Decision making model:
  CHMP-EC

Key dates and outcomes

• CHMP opinion date:
  19/05/2022
• EC decision date:
  18/07/2022

All documents

European Commission final decision

Daruph and Anafezyn Article 29(4) referral - Annex I

Daruph and Anafezyn Article 29(4) referral - Annex II

Daruph and Anafezyn Article 29(4) referral - Annex III

Daruph and Anafezyn Article 29(4) referral - EMA recommends authorisation of Daruph / Anafezyn (dasatinib anhydrous) in the EU

Reference Number: EMA/662970/2022

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.