This observational, multicenter, retrospective and prospective study aims to evaluate the effect of lomitapide treatment on Major Adverse Cardiovascular Events (MACE) in patients with Homozygous Familial Hypercholesterolemia (HoFH).

HoFH is a rare genetic disorder characterized by extremely high levels of LDL cholesterol (LDL-C), leading to an increased risk of early cardiovascular diseases. Lomitapide is an approved medication that lowers LDL-C levels by inhibiting microsomal triglyceride transfer protein (MTP).

The study will collect data from patients who have been treated with lomitapide for at least 12 months and will compare the incidence of MACE during the first three years of treatment with the three years before treatment initiation. The study includes data collection from multiple lipid centers across Europe.

The primary objective is to assess the impact of lomitapide on MACE, while secondary objectives include evaluating changes in lipid profiles, liver function tests, and lipid-lowering treatments.

This is a multicenter, international, long-term observational study investigating the real-world impact of lomitapide on Major Adverse Cardiovascular Events (MACE) in patients with Homozygous Familial Hypercholesterolemia (HoFH).

Study Design:

Observational, open-label, retrospective and prospective study Data will be collected from 30 lipid centers across Europe Patients will serve as their own control, with comparisons between pre-treatment (3 years before lomitapide) and post-treatment (first 3 years of lomitapide therapy) periods

Study Population:

Approximately 72 adult patients (≥18 years) diagnosed with HoFH Patients must have received lomitapide for at least 12 months Availability of 3 years of pre-treatment clinical records

Objectives:

Primary Objective: Evaluate the incidence of MACE before and after lomitapide treatment

Secondary Objectives: Assess changes in LDL-C, total cholesterol, liver function tests (ALT, AST, GGT), and lipid-lowering therapy usage (e.g., discontinuation of LDL apheresis, addition of PCSK9 inhibitors)

Endpoints:

Primary Endpoint: Change in MACE incidence over the 3-year treatment period

Secondary Endpoints: Changes in lipid levels, liver safety markers, and adherence to treatment protocols

Safety Considerations:

The study follows real-world clinical practice, with monitoring of adverse events, including liver-related safety concerns associated with lomitapide

Data will be collected in an electronic Case Report Form (eCRF) and analyzed following Good Clinical Practice (GCP) guidelines

This study aims to generate real-world evidence on the cardiovascular impact of lomitapide in HoFH patients, addressing an unmet clinical need for data on long-term outcomes.

Inclusion Criteria:

• Adult patients (age ≥18 years)
• Clinical or genetic diagnosis of HoFH
• Treated with lomitapide at any dosage
• On treatment with lomitapide for at least 12 months at the time of enrollment
• Availability of 3 years of medical records prior to lomitapide treatment to confirm MACE
• Giving written informed consent

Exclusion Criteria:

• Patients who were prescribed lomitapide outside of the marketing authorization or in contraindicated patients
• Patients receiving lomitapide in clinical trials
• Patients receiving an investigational agent, defined as any drug or biologic agent other than lomitapide that has not received Market Authorization in the country of participation, at the time of enrolment

Patients with a clinical or genetic diagnosis of homozygous familial hypercholesterolemia (HoFH) who have been treated with lomitapide for at least 12 months.

The LILITH study collects observational data on patients treated with lomitapide in compliance with data protection regulations (GDPR) and Good Clinical Practice (GCP) guidelines. At this time, individual participant data (IPD) sharing is not planned to ensure confidentiality and adherence to ethical and legal requirements. However, aggregated study results will be made available through scientific publications and regulatory reports.