Background and Aims

To evaluate the long-term hepatic safety of lomitapide in patients with homozygous familial hypercholesterolaemia (HoFH).

Methods

Patient data were aggregated from the pivotal phase 3 and extension phase clinical trial with lomitapide (n=29) (median 5.1 years; serum total bilirubin, transaminases, cytokeratin-18 [CK-18] and enhanced liver fibrosis [ELF] score; 8-year data from the Lomitapide Observational Worldwide Evaluation Registry (LOWER) (n=214) and real-world evidence from a cohort of patients treated with lomitapide in Italy from the Italian Lomitapide Working Group in HoFH (n=34) (hepatic ultrasound, hepatic elastography, and FIB-4 score for hepatic fibrosis).

Results

In the phase 3 trial and LOWER registry, mild/moderate elevations in liver transaminase levels were observed without elevations in bilirubin (i.e., no Hy’s law cases). Evaluating hepatic biomarkers from the phase 3 dataset confirmed there were no clinically relevant increases in CK-18, CK-18 fragments, or ELF score.

Data from LOWER affirmed that no specific statin or other lipid-lowering combinations were more prone to cause liver function tests elevations when prescribed with lomitapide.

In the Italian patients treated with lomitapide for up to 9.5 years, 68% had no change in their hepatic fat versus baseline and 32% had an increase, with all elevations in the mild to moderate range. Hepatic elasticity remained normal for all patients (Figure 1) and the mean FIB-4 score remained below the fibrosis threshold value of 2.67.

Conclusions

Overall, the hepatic safety of lomitapide remains favourable with no clinically significant elevations in hepatic biomarkers and hepatic elasticity remained normal for up to 9.5 years in patients with HoFH.