Long-term efficacy and safety of lomitapide in patients with familial chylomicronemia syndrome: Data from an expanded access program.

BACKGROUND

Familial chylomicronemia syndrome (FCS) is a rare, severe, autosomal recessive disorder characterized by extremely high triglyceride (TG) levels and an increased risk of acute and/or recurrent pancreatitis. Lomitapide, a microsomal triglyceride transfer protein (MTP) inhibitor, is approved for the treatment of homozygous familial hypercholesterolemia. The open-label, single-arm LOCHNES study (EudraCT 2018-002911-80) investigated lomitapide in adult patients with genetically confirmed FCS and a history of pancreatitis, demonstrating its efficacy and tolerability.

METHODS

Fourteen patients previously enrolled in the LOCHNES study were admitted to the Lomitapide Expanded Access Program 2 months after study completion. They were followed every 3 months over a nearly 3-year period (median follow-up: 33 months), continuing lomitapide at the maximum tolerated dose established during the trial. Evaluations included lipid profile, liver function tests, hepatic fat content, and liver stiffness.

RESULTS

At the start of the follow-up period (after a 2-month lomitapide washout), median TG levels were 1899.5 mg/dL (range: 1013.5-2572 mg/dL). At the last observation, median fasting TGs were reduced to 376.5 mg/dL (range: 195-1328 mg/dL), representing a 80.2% decrease; 9 patients achieved TG levels ≤750 mg/dL. Adverse events were mostly mild-to-moderate, predominantly gastrointestinal (n = 11). Two patients experienced an episode of acute pancreatitis during follow-up. Liver enzymes ≥3 × the upper limit of normal were observed in 2 patients. Hepatic fat content increased in 3 patients, while median liver stiffness remained within the normal range.

CONCLUSIONS

Lomitapide effectively and safely reduced TG levels in FCS patients with a history of pancreatitis over a nearly 3-year follow-up period. These findings are consistent with those of the open-label trial, despite the use of a lower median daily dose (27 mg). No new safety signals were observed.