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

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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.

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