General Information

Ocaliva (obeticholic acid) is a farnesoid X receptor (FXR) agonist.

Ocaliva is specifically indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA, or as monotherapy in adults unable to tolerate UDCA.

Mechanism of Action

Ocaliva (obeticholic acid) is a farnesoid X receptor (FXR) agonist. FXR is a nuclear receptor expressed in the liver and intestine. FXR is a key regulator of bile acid, inflammatory, fibrotic, and metabolic pathways. FXR activation decreases the intracellular hepatocyte concentrations of bile acids by suppressing de novo synthesis from cholesterol as well as by increased transport of bile acids out of the hepatocytes. These mechanisms limit the overall size of the circulating bile acid pool while promoting choleresis, thus reducing hepatic exposure to bile acids.

Side Effects

Adverse effects associated with the use of Ocaliva may include, but are not limited to, the following:

• Pruritus
• Fatigue
• Abdominal pain and discomfort
• Rash
• Oropharyngeal pain
• Dizziness
• Constipation
• Arthralgia
• Thyroid function abnormality
• Eczema

Dosing/Administration

Ocaliva is supplied as tablets for oral administration. The recommended starting dosage of Ocaliva is 5 mg orally once daily in adult patients who have not achieved an adequate biochemical response to an appropriate dosage of UDCA for at least one year or are intolerant to UDCA. Dosage Titration: If an adequate reduction in ALP and/or total bilirubin has not been achieved after three months of Ocaliva 5 mg once daily, and the patient is tolerating Ocaliva, increase the dosage of Ocaliva to 10 mg once daily. The maximum recommended dosage of Ocaliva is 10 mg once daily. Please see drug label for specific dose adjustments.

Clinical Trial Results

FDA Approval

The FDA approval of Ocaliva was based on the phase 3 POISE trial, which studied the safety and efficacy of once-daily treatment with Ocaliva in PBC patients with an inadequate therapeutic response to, or who are unable to tolerate, UDCA. The POISE data showed that Ocaliva, at both a 10-mg dose and a 5-mg dose titrated to 10 mg, met the trial's primary end point of achieving a reduction in serum ALP to below a threshold of 1.67 times the upper limit of normal, with a minimum of 15 percent reduction in ALP level from baseline and a normal bilirubin level after 12 months of therapy. Pruritus was the most frequently reported adverse event associated with Ocaliva treatment. In a group of patients who initiated Ocaliva at a 5-mg once-daily dose and titrated up to 10 mg once daily, one patient (1 percent) discontinued from the study due to pruritus as compared to seven patients (10 percent) in the 10-mg dose group and after 12 months of treatment, efficacy was essentially equivalent to those patients who started the study at the 10-mg dose.