Description

This ERN Rare-Liver webinar, held on 08 July 2024, is discussing the decision of the European Medicines Agency to recommend withdrawal of the conditional market authorisation of Ocaliva, a second-line drug for PBC consisting of the chemical obeticholic acid. The drug was incensed in 2016 on the basis of the POISE trial, a randomised study that showed a marked lowering of alkaline phosphatase (AP), the liver enzyme that is rated in blood in almost all PBC patients. Previous studies had shown that the level of AP increase in PBC patients appears to correlate with the long-term prognosis of the disease. Furthermore, it was shown that the standard therapy for PBC, Ursodeoxycholic acid (UDCA), lowers AP in most patients, and that the more AP was lowered the better the prognosis.

It was therefore that AP became a surrogate marker for treatment effectiveness in PBC, and that obeticholic acid was presumed to improve the prognosis because of its effective lowering of AP. However, as a surrogate marker is just a surrogate, the EMA had given market authorisation to Ocaliva only on the condition that the effectiveness of the drug be demonstrated by a long-term randomised trial. The results of this long term trial, study 747-302, were now presented to the EMA and analysed in detail. Overall, neither overall survival nor the need for liver transplantation were improved in the treatment group compared with the placebo group. Therefore, EMA concluded, after careful discussion with external experts, patient groups and representatives of the pharmaceutical company, that the benefits of the drug do not outweigh its potential risks, and therefore recommended withdrawal from the market. Another aspect was the increase in itching as one of the most bothersome symptoms of PBC. In addition to the 747-302 trial, various studies based on real world data were also looked at.

In view of this recommendation, what does this mean for patients, and which recommendations should be made by physicians looking after PBC patients? Specific points to be discussed are:

  • Should patients on Ocaliva try to continue the drug by compassionate use, if provided by the company?
  • Should patients be switched to other second-line agents, in particular bezafibrate?
  • Is there a role for immunosuppressive therapy in UDCA non-responders?
  • How promising are the newly developed, but not yet licensed drugs elafibrinor and sedalpar?
  • What is the role of AP as surrogate marker? Should it be substituted by liver stiffness measurements?
  • Which therapies address the symptoms of the disease, and is symptom-oriented therapy not more important than slowing fibrosis progression?

Targeted Audience

  • General practitioners
  • Hepatologists
  • Oncologists
  • Health care professionals
  • Patients

Faculty

Participants

  • Alessio Gerussi, Azienda Sanitaria Socio Assistenziale (ASST)-Monza, Ospedale San Gerardo, Co-lead PBC working Group
  • Adriaan van der Meer, Erasmus MC: University Medical Center Rotterdam, Co-lead PBC working Group
  • Angela Leburgue, Patient lead PBC working group
  • Christophe Corpechot, Hôpital Saint-Antoine, APHP Paris
  • Michael Trauner, Medical University of Vienna

Moderator

  • Ansgar W. Lohse, Coordinator ERN RARE-LIVER

Round-table discussion: Second line therapy after the EMA recommendation to withdraw Ocaliva

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