Long-term, real-world data on lomitapide for HoFH

A single-center retrospective case series of 6 patients with homozygous familial hypercholesterolemia (HoFH) showed lomitapide reduced LDL-c by 69% from baseline for up to 7 years and was generally well tolerated.

This summary is based on the publication of Suppressa P, Coppola C, Cocco V, et al. - Long-term effectiveness and safety of lomitapide in patients with homozygous familial hypercholesterolemia: an observational case series. Orphanet J Rare Dis. 2024 Oct 8;19(1):370. doi: 10.1186/s13023-024-03374-9

Introduction and methods

Background

Despite combination therapy with lipid-lowering agents, most patients with homozygous familial hypercholesterolemia (HoFH) do not reach guideline-recommended LDL-c goals [1]. Lomitapide, an oral, selective inhibitor of microsomal triglyceride transfer protein, has been approved as adjunct treatment for adults with HoFH [2]. However, real-world data on the long-term effectiveness and safety in various treatment settings are lacking.

Aim of the study

The authors assessed real-world evidence on the long-term effectiveness and safety of lomitapide in HoFH patients, with regard to LDL-c reduction, LDL-c goal achievement, changes in concomitant lipid-lowering therapies, CV symptoms and events, and hepatic safety.

Methods

This was an observational retrospective case series of 6 patients (4 males, 2 females) with a genetic diagnosis of HoFH who were treated with lomitapide, in addition to a low-fat diet, at the University Hospital of Bari in Bari, Italy. Clinical information was collected up to February 2023. At baseline, all participants were on statin therapy and ezetimibe, and 4 of them were also being treated with a PCSK9 inhibitor. Median duration of lomitapide treatment was 47 months (IQR: 25–68; range: 18–85), and the mean lomitapide dose was 17.5 mg/day; range: 5–40).

Outcomes

The primary endpoint was the change in LDL-c levels from baseline to the last follow-up visit. Additional endpoints included the number of patients achieving the LDL-c targets for HoFH recommended by the European Atherosclerosis Society in 2023 (<70 mg/dL, or <55 mg/dL in case of additional ASCVD risk factors or established ASCVD) [3] at any time during follow-up, and changes from baseline to last follow-up visit in HDL-c, ALT/AST, and gamma glutamyl transferase (GGT) levels and CV events. Safety assessment included the incidence of adverse events, including any occurrence of ALT/AST >3 the upper limit of normal (ULN).

Main results

Effectiveness

• At baseline, the mean LDL-c level was 263.2 mg/dL (SD: 148.1), which decreased by 69% during lomitapide treatment to 81.3 mg/dL (SD: 30.5) at last follow-up. The mean LDL-c level at nadir was 52.8 mg/dL (SD: 19.2)—an 80% reduction from baseline.

• Four patients (66.7%) achieved LDL-c <70 mg/dL at some point during follow-up, all of whom also achieved LDL-c <55 mg/dL.

• Lomitapide did not reduce HDL-c levels between baseline (49.5 mg/dL; SD: 16.0) and the last follow-up visit (51.3 mg/dL; 12.8).

• From baseline to the last follow-up visit, mild, clinically nonsignificant increases in ALT and AST levels <3 ULN and a minimal change in GGT levels were observed.

• Hepatic steatosis was mild-to-moderately severe in 5 patients and absent in the last patient. Hepatic elasticity remained normal in all but 2 older patients (aged >70 years).

• All patients with CV symptoms at baseline experienced a reduction during lomitapide treatment. However, the authors could not establish a causal relationship between lomitapide treatment and CV outcomes.

• All patients showed stabilization or regression of carotid intima-media thickness and atheromatous plaques.

Safety

• Adverse events were generally mild to moderate in severity and mainly consisted of diarrhea (n=3).

• One patient had ALT/AST >3 ULN, which was managed by lowering the lomitapide dose.

Conclusion

This Italian, retrospective case series of 6 HoFH patients showed that lomitapide treatment—in addition to a low-fat diet, statin therapy, and ezetimibe—reduced LDL-c levels by 69% from baseline for up to 7 years. Most patients achieved their LDL-c goals at some point, and lomitapide was generally well tolerated.

Find this article online at Orphanet J Rare Dis.

References

1. Tromp TR, Hartgers ML, Hovingh GK, et al. Worldwide experience of homozygous familial hypercholesterolaemia: retrospective cohort study. Lancet Feb. 2022;19(10326):719–28. https://doi.org/10.1016/s0140-6736(21)02001-8.
2. Amryt Pharmaceuticals DAC. Lojuxta Summary of Product Characteristics. 2021. 3. Cuchel M, Raal FJ, Hegele RA, et al. 2023 Update on European Atherosclerosis Society Consensus Statement on homozygous familial hypercholesterolaemia: new treatments and clinical guidance. Eur Heart J May. 2023;2. https://doi.org/10.1093/eurheartj/ehad197.