ELAFIBRANOR TAB

Clinical Criteria Summary

Treatment of primary biliary cholangitis (PBC) in combination with ursodiol (UDCA) in adults with an inadequate response to UDCA
Monotherapy in patients unable to tolerate UDCA
Accelerated approval based on reduction of alkaline phosphatase (ALP); improvement in survival or prevention of liver decompensation events has not been demonstrated

Use not recommended in patients who have or develop decompensated cirrhosis (e.g., ascites, variceal bleeding, hepatic encephalopathy)
Avoid use in decompensated liver disease

Renal impairment (mild, moderate, or severe): No dosage modification recommended
Mild hepatic impairment: No dosage modification required
Moderate or severe hepatic impairment (Child-Pugh B or C) or progression to the same: Consider discontinuing therapy
Worsening liver tests after restarting elafibranor in patients with drug-induced liver injury (DILI): Consider discontinuing therapy

New onset or worsening of muscle injury, muscle pain, myopathy, or rhabdomyolysis
Worsening liver tests or evidence of clinical hepatitis in patients with DILI
Hypersensitivity reactions
Suspected biliary obstruction

Recommended as add-on therapy to UDCA in patients with PBC without decompensated cirrhosis who have an inadequate response to UDCA
Monotherapy reserved for patients with intolerance to UDCA
An adequate trial of UDCA is defined as at least 1 year at a dosage of 13–15 mg/kg/d, with ≥ 3 months at a stable dosage
No dosage adjustment necessary for patients ≥65 years; closer monitoring of adverse effects recommended for patients >75 years
Efficacy not significantly impacted by body weight (43–120 kg) or BMI (14.5–54 kg/m²)

Documented diagnosis of primary biliary cholangitis (PBC) without cirrhosis or PBC with compensated cirrhosis and no evidence of portal hypertension

Decompensated cirrhosis (e.g., Child-Pugh Class B or C) or a prior decompensation event, including hepatorenal syndrome, MELD ≥ 12, hepatocellular carcinoma, hepatic encephalopathy, international normalized ratio (INR) > 1.3, platelet count < 150
Compensated cirrhosis with evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia)
Complete biliary obstruction
Severely advanced primary biliary cholangitis (PBC) defined as total bilirubin greater than upper limit of normal (ULN) and albumin less than the lower limit of normal
Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 5 times the ULN
Creatine phosphokinase (CPK) > 2 times the ULN
Other chronic liver conditions, such as primary sclerosing cholangitis, autoimmune hepatitis, metabolic dysfunction-associated steatohepatitis (MASH), and alpha-1 antitrypsin deficiency
Myopathy or rhabdomyolysis
Pregnancy
Lactating

Tried ursodiol monotherapy (unless medically inadvisable) and had intolerance or inadequate response after 12 months (stable dose for at least 3 months at 13 to 15 mg/kg/day)

Prescribed and monitored by a VA or VA Community Care hepatologist or locally designated expert in primary biliary cholangitis (PBC)

Pregnancy has been excluded prior to receiving elafibranor
For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment; counseling provided on the use of effective non-hormonal contraception or addition of a barrier method to hormonal contraceptives during therapy and for 3 weeks after the last dose