Ocaliva - referral

Current status

Under evaluation

Overview

EMA’s human medicines committee (CHMP) has started a review of the medicine Ocaliva (obeticholic acid), used to treat adults with primary biliary cholangitis (PBC). PBC is an autoimmune condition that causes gradual destruction of the small bile ducts in the liver, which can lead to liver failure and increase the risk of liver cancer.

The review was prompted by the final results from two studies in patients with PBC, which were requested by EMA in 2016 as part of the conditions to the initial marketing authorisation of Ocaliva. Study 747-302 was designed to confirm the benefits and safety of Ocaliva, while study 747-401 assessed the safety of Ocaliva in patients with advanced liver disease.

In particular, study 747-302 failed to show that Ocaliva was more effective than placebo (a dummy treatment) in terms of the number of patients whose disease worsened or who died. In addition, side effects, including serious ones, occurred more frequently in patients treated with Ocaliva.

EMA will now review these findings alongside all other available data and assess their impact on the overall benefit-risk balance of Ocaliva. The Agency will then make a recommendation on whether the medicine’s marketing authorisation in the EU should be amended.

More about the medicine

Ocaliva (obeticholic acid) is used to treat adults with primary biliary cholangitis, an autoimmune condition in which there is gradual destruction of the small bile ducts in the liver. As a result of the damage to the biliary ducts, bile builds up in the liver causing damage to the liver tissue. This may lead to scarring and liver failure, and may increase the risk of liver cancer. Ocaliva is used together with another medicine, ursodeoxycholic acid (UDCA), in patients who do not respond sufficiently to UDCA alone, and on its own in patients who cannot take UDCA.

Primary biliary cholangitis is rare, and Ocaliva was designated an ‘orphan medicine’ (a medicine used in rare diseases) on 27 July 2010.

Ocaliva was granted a conditional marketing authorisation in December 2016. Conditional authorisation is granted on the basis of less comprehensive data than are normally required. It is granted for medicines that fulfil an unmet medical need to treat serious diseases and when the benefits of having them available earlier outweigh any risks associated with using the medicines while waiting for further evidence.

At the time of approval, the main study showed that Ocaliva reduced the blood levels of the substances bilirubin and ALP (markers of liver damage) in patients with primary biliary cholangitis, including those who could not be treated with UDCA. Reductions in bilirubin and ALP were considered to be indicators for future improvements in the condition of the liver. However, the benefits of Ocaliva needed to be confirmed in further studies.

The medicine was therefore granted a marketing authorisation on condition that the company provided further data on its benefits and safety from two additional studies (study 747-302 and study 747-401).

More information about the medicine can be found on the EMA website.

More about the procedure

The review of Ocaliva has been initiated at the request of the European Commission, under Article 20 of Regulation (EC) No 726/2004.

The review is being carried out by the Committee for Medicinal Products for Human Use (CHMP), responsible for questions concerning medicines for human use, which will adopt the Agency’s opinion. The CHMP opinion will then be forwarded to the European Commission, which will issue a final legally binding decision applicable in all EU Member States.

Ocaliva Article 20 procedure : Review of Ocaliva started

Reference Number: EMA/458857/2023

Key facts

About this medicine

• Approved name:
  Ocaliva
• International non-proprietary name (INN) or common name:
  obeticholic acid
• Associated names:
  Ocaliva
• Class:
  Bile acids and derivatives

About this procedure

• Current status:
  Under evaluation
• Reference number:
  EMEA/H/A-20/1531/C/004093/0045
• 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.

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

All documents

Procedure started

Ocaliva Article 20 procedure : Notification

Ocaliva Article 20 procedure : CHMP list of questions

Reference Number: EMA/CHMP/449195/2023

Ocaliva Article 20 procedure : Review of Ocaliva started

Reference Number: EMA/458857/2023

Under evaluation

Ocaliva Article 20 procedure : Timetable for the procedure

Reference Number: EMA/CHMP/448947/2023 Rev.4

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.