[PIO] European Medicines Agency recommends withdrawal of conditional marketing authorisation for Ocaliva

The Committee for Medicinal Products for Human Use (CHMP) has completed its review of Ocaliva (obeticholic acid) and recommends the withdrawal of the marketing authorisation for the medicine as it is no longer considered that the benefits outweigh the risks associated with this treatment. The medicine Ocaliva is used to treat adult patients with primary biliary biliary cholangitis (PBC), an autoimmune condition that causes gradual destruction of the bile ducts in the liver and which can lead to liver failure and increase the risk of liver cancer.

At the time of its conditional marketing authorisation in 2016, Ocaliva was shown to reduce blood levels of alkaline phosphatase (ALP) and bilirubin (markers of liver damage) in patients with PBC, and this was considered indicative of an improvement in the liver condition. However, the clinical benefits of Ocaliva needed to be documented in further studies, which were requested by the EMA as part of the conditions for the marketing authorisation for the drug. In particular, the study 747-302 was a randomized clinical trial aimed at confirming the clinical benefits and safety of Ocaliva in patients for whom ursodeoxycholic acid (UDCA, another drug for PBC) does not work well enough or who cannot take UDCA.

The CHMP has now evaluated the findings of this study, along with other available data, including real world data and data from supporting studies submitted by the company marketing Ocaliva, as well as information submitted by healthcare professional and patient associations. In addition, the CHMP took into account feedback from a panel of liver disease experts who provided their views on specific questions raised by the CHMP, as well as views from people with experience of PBC.

After reviewing the available evidence, the Committee concluded that the clinical benefits of Ocaliva have not been confirmed. Specifically, Study 747-302 failed to show that Ocaliva was more effective than placebo (placebo) in terms of the number of patients whose disease worsened or who died, both in the overall population and in a cohort of patients with early-stage PBC.

The Committee also found that data from supporting studies and real-world data were insufficient to confirm the benefits of Ocaliva and could not offset the negative results of the 747-302 study. Therefore, the CHMP concluded that the benefits of Ocaliva did not outweigh its risks and recommended the withdrawal of the marketing authorisation of the medicine in the European Union (EU).

The EMA will now send the CHMP opinion to the European Commission, which will in due course issue a final, legally binding, decision applicable in all EU Member States.

Patient information

1. A recent study failed to confirm that the drug Ocaliva (obeticholic acid/obeticholic acid) is effective in treating primary biliary cholangitis (PBC, an autoimmune condition that causes gradual destruction of small bile ducts in the liver).
2. The 747-302 study failed to show that Ocaliva was more effective than placebo (placebo) in terms of the number of patients whose disease worsened or who died, both in the overall population and in a group of patients with early-stage PBC.
3. The EMA Committee for Medicinal Products for Human Use (CHMP) has therefore recommended the withdrawal of Ocaliva from the European Union market as the benefits are no longer considered to outweigh the risks of the medicine.
4. Once this recommendation is confirmed by the European Commission, Ocaliva will no longer be authorised in the EU. The company may, however, continue to provide the medicine through palliative or name-based programmes to patients already taking Ocaliva.
5. If you are taking Ocaliva, you should talk to your doctor about this decision and what it means for you and your treatment.

Information for healthcare professionals

1. A review of available data concluded that the clinical benefits of Ocaliva (obeticholic acid/obeticholic acid), used to treat primary biliary cholangitis (PBC), have not been confirmed.
2. In particular, the 747-302 study failed to show differences between Ocaliva and placebo for the primary composite endpoint of death, liver transplantation or hepatic antitransplantation in the overall population of patients with PBC who are either unresponsive or intolerant to ursodeoxycholic acid (HR 1).01 [95%CI: 0.68, 1.51], p-value: 0.954).
3. Therefore, the EMA recommended the withdrawal of the marketing authorisation of Ocaliva in the European Union because it is no longer considered that the benefits outweigh the risks of the drug.
4. Once this recommendation is confirmed by the European Commission, Ocaliva will no longer be authorised in the EU. The company may, however, continue to provide the medicine through palliative care or name-based programmes to existing patients.
5. Healthcare professionals should not initiate treatment with Ocaliva in new patients outside of a clinical trial setting. For patients currently being treated with Ocaliva, consideration should be given to available treatment options.

A direct to healthcare professional communication (DHPC) will be sent in a timely manner to healthcare professionals who prescribe, dispense, or administer the drug. The DHPC will also be published on a dedicated page on the EMA website.

More about the drug

Ocaliva (obeticholic acid/obeticholic acid) is used to treat adults with primary biliary cholangitis (PBC), an autoimmune condition in which there is gradual destruction of the bile ducts in the liver. As a result of damage to the bile ducts, bile builds up in the liver causing damage to liver tissue. This can lead to scarring and liver failure and may increase the risk of liver cancer. Ocaliva is used along with another drug, ursodeoxycholic acid (UDCA) in patients who do not respond adequately to UDCA monotherapy, and as monotherapy in patients who cannot receive UDCA.

PBC is a rare disease and Ocaliva was designated as an "orphan drug" (a drug used in rare diseases) on 27 July 2010.

Ocaliva received conditional marketing authorization in December 2016. A conditional marketing authorisation allows a drug to be licensed on the basis of less comprehensive data than is normally required. It is granted to medicines that meet an unmet medical need for the treatment of serious diseases and when the benefits of making them available earlier outweigh the risks associated with their use pending further data.

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

The drug was therefore granted 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 drug can be found on the EMA website.

More about the process

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

The review was conducted by the Committee for Medicinal Products for Human Use (CHMP), responsible for matters relating to medicinal products for human use, which issued the Agency's opinion. The CHMP opinion will now be forwarded to the European Commission, which will adopt a final legally binding decision applicable in all EU Member States.

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