Real-world long-term data on lomitapide in HoFH

ESC 2026 – Real-world data from the global prospective LOWER registry over 11 years support the long-term effectiveness and safety of lomitapide in patients with HoFH.

This summary is based on the poster presentation of Dirk Blom, PhD (Cape Town, South Africa) at the EAS 2026 - Long-term safety and effectiveness of lomitapide in treating homozygous familial hypercholesterolemia: 11 years of real-world evidence from the Lomitapide Observational Worldwide Evaluation Registry (LOWER).

Introduction and methods

Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by extremely elevated LDL-c levels, often leading to premature cardiovascular disease and mortality. Lomitapide is an oral microsomal triglyceride transfer protein (MTP) inhibitor that reduces LDL-c levels independently of the LDL receptor pathway. Lomitapide is approved for the treatment of HoFH.

The LOWER (Lomitapide Observational Worldwide Evaluation Registry) registry, which was initiated in 2014, is a global, prospective, observational cohort study of the long-term effectiveness and safety of lomitapide in clinical practice across sites in the US, Europe, Canada, Argentina, and Taiwan.

The aim of this analysis was to report on 11-year follow-up data from patients enrolled in LOWER. A total of 246 patients (mean age 50.3 years, 56.5% females) has enrolled in LOWER, witch treatment data available for 245 patients. Mean ± SD LDL-c level at baseline was 241.1 ± 109.1 mg/dL.

Main results

Efficacy data

• Patients treated with lomitapide achieved substantial LDL-c reductions for up to 11 years.
• At any time during follow-up, 72% of the patients had an LDL-c reduction ≥50% from baseline.
• 74% of the patients achieved LDL-c <100 mg/dL, 51% of the patients achieved <70 mg/dL and 38% reached <55mg/dL at any time during follow-up.
• The incidence of MACE during lomitapide treatment was 2.8 events per 100 person-years. After lomitapide discontinuation, the incidence of MACE was 4.3 events per 100 person-years.

Safety data

• The most common events of special interest were hepatic events (21.6%), followed by MACE (15.9%) and gastrointestinal events (13.9%).
• Any adverse event occurred in 75.1% of the patients. Gastrointestinal disorders occurred in 45.3% of the patients.

Conclusion

Data from the global prospective LOWER registry over 11 years demonstrated that treatment with lomitapide leads to substantial and sustained LDL-c reductions in patients with HoFH in real-world clinical practice, with 74% of the patients achieving LDL-c <100 mg/dL. The safety profile of lomitapide appeared manageable.

- Our reporting is based on the information provided at the EAS 2026 -