Taking into consideration the inability to establish the safety and efficacy of Obeticholic acid ( Ocaliva ) through clinical trials in patients with primary biliary cholangitis ( PBC ) with decompensated liver cirrhosis, or with a prior history of hepatic decompensation, as well as new safety information from post-marketing reports, the use of Obeticholic acid is now contraindicated in patients with primary biliary cholangitis and with decompensated cirrhosis ( including Child-Pugh Class B or C ) or a prior decompensation event.
• Treatment should be discontinued in patients with primary biliary cholangitis and with decompensated cirrhosis currently receiving Obeticholic acid.
• Patients should be routinely monitored for progression of primary biliary cholangitis and treatment with Obeticholic acid should be permanently discontinued in patients with laboratory or clinical evidence of hepatic decompensation including progression to Child-Pugh class B or C.
• Treatment with Obeticholic acid should not be started if the patient has decompensated cirrhosis or a history of a decompensation event prior to treatment initiation.
Obeticholic acid is a farnesoid X receptor ( FXR ) agonist and a modified bile acid. It received conditional marketing authorization in December 2016 for the treatment of primary biliary cholangitis, in combination with Ursodeoxycholic acid ( UDCA ), in adults with an inadequate response to UDCA, or as monotherapy in adults unable to tolerate UDCA.
Interim analysis results from the studies intended to confirm efficacy and safety in patients with primary biliary cholangitis and with decompensated cirrhosis ( moderate to severe hepatic impairment ), i.e. study 747-401, and in a broader PBC population, i.e. study 747-302, were deemed highly likely to be futile by the trials’ independent data monitoring Committee.
Given the difficulties completing the studies, the limited information available to further inform benefit / risk, and the medically more fragile nature of patients with primary biliary cholangitis and decompensated cirrhosis, the SmPC ( summary of product characteristics ) is being updated to contraindicate the use of Obeticholic acid in these patients.
In addition, available safety data from post-marketing reports in patients with primary biliary cholangitis and with cirrhosis have also been considered, i.e. cases of hepatobiliary disorders, including hepatic failure and hepatic cirrhosis, for which there is a possibility of a causal association with Obeticholic acid treatment.
As a consequence, section 4.3 ( Contraindications ) of the SmPC is being updated to reflect the contraindication of Obeticholic acid in patients with decompensated cirrhosis ( e.g. Child-Pugh class B or C ) or a prior decompensation event, and section 4.4 ( Special warnings and precautions ) will include new information about hepatic decompensation and failure, sometimes fatal or resulting in liver transplant, occurring with Obeticholic acid treatment in patients with PBC with cirrhosis, either compensated or decompensated.
Section 4.8 ( Undesirable effects ) is also being updated to include hepatobiliary disorders in the tabulated list of adverse reactions.
Additional changes in relation to the use of Obeticholic acid in patients with concomitant hepatic disease and severe intercurrent illness will also be made throughout the SmPC. ( Xagena )
Source: EMA, 2022