OCALIVA

What it is

OCALIVA contains the active ingredient obeticholic acid in strengths of 5 mg or 10 mg per tablet. The 5 mg tablets are yellow round tablets, and the 10 mg tablets are yellow triangular tablets. Obeticholic acid is a selective and potent agonist for the farnesoid X receptor (FXR), a nuclear receptor expressed at high levels in the liver and intestine.

Approved indications

— Primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA. — Primary biliary cholangitis (PBC) as monotherapy in adults unable to tolerate UDCA.

Dosing overview

The starting dosage of obeticholic acid is 5 mg once daily for the first 6 months. After the first 6 months, for patients who have not achieved an adequate reduction in alkaline phosphatase (ALP) and/or total bilirubin and who are tolerating obeticholic acid, increase to a maximum dosage of 10 mg once daily. The tablet should be taken orally with or without food.

Key safety warnings

Hepatic failure, sometimes fatal or resulting in liver transplant, has been reported with OCALIVA treatment in primary biliary cholangitis (PBC) patients with either compensated or decompensated cirrhosis. Liver tests should be obtained before initiating treatment with OCALIVA, within the first 6 months after initiation of treatment, and as clinically indicated thereafter. After initiation of therapy, all patients should be routinely monitored for progression of PBC, including hepatic adverse reactions, with laboratory and clinical assessment to determine whether obeticholic acid treatment discontinuation is needed. Severe pruritus was reported in 23% of patients treated with OCALIVA 10 mg arm, 19% of patients in the OCALIVA titration arm, and 7% of patients in the placebo arms. Management strategies include the addition of bile acid binding resins or antihistamines, dose reduction, reduced dosing frequency, and/or temporary dose interruption. Patients with PBC generally exhibit hyperlipidemia characterised by a significant elevation in total cholesterol primarily due to increased levels of high-density lipoprotein-cholesterol (HDL-C). In the phase III clinical study, dose-dependent reductions from baseline in mean HDL-C levels were observed at 2 weeks in OCALIVA-treated patients, 20% and 9% in the 10 mg and titration arms, respectively, compared to 2% in the placebo arm. At month 12, the reduction from baseline in mean HDL-C level was 19% in the OCALIVA 10 mg arm, 12% in the OCALIVA titration arm, and 2% in the placebo arm.

Contraindications

OCALIVA is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients, patients with decompensated cirrhosis (such as Child-Pugh Class B or C) or a prior decompensation event, patients with compensated cirrhosis who have evidence of portal hypertension (such as ascites, gastroesophageal varices, persistent thrombocytopenia), and patients with complete biliary obstruction.

PBS listing

OCALIVA 5 mg tablets are listed on the PBS with 2 items under authority required and streamlined restrictions at an ex-manufacturer price of A$3631.00. OCALIVA 10 mg tablets are listed on the PBS with 1 item under streamlined restriction at an ex-manufacturer price of A$3631.00.

Regulatory history

OCALIVA was first registered on the ARTG on 21 September 2018, with both the 5 mg and 10 mg strengths listed as licence category RE. The PBAC recommended OCALIVA for primary biliary cholangitis in March 2021. This medicinal product is subject to additional monitoring in Australia.