Long-term real-world data on MTP inhibitor in adult HoFH


EAS 2024 - Real-world data from the global prospective LOWER registry over 9 years showed ~75% of the 223 adults with homozygous familial hypercholesterolemia (HoFH) achieved LDL-c <100 mg/dL with lomitapide and almost half reached LDL-c <70 mg/dL. No new safety concerns were identified.

This summary is based on the presentation of Dirk Blom, PhD (Cape Town, South Africa) at the EAS Congress 2024 - The long-term, real-world effectiveness and safety of lomitapide in homozygous familial hypercholesterolaemia (HoFH): Nine-year data from the Lomitapide Observational Worldwide Evaluation Registry (LOWER).

Introduction and methods

Lomitapide is an oral microsomal triglyceride transfer protein (MTP) inhibitor that reduce LDL-c levels independently of the LDL receptor pathway. The FDA and EMA approved lomitapide for the treatment of adult patients with homozygous familial hypercholesterolemia (HoFH), although the FDA mandated a postapproval, long-term, observational registry study on its effectiveness and safety.

The LOWER (Lomitapide Observational Worldwide Evaluation Registry) registry 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. Patient enrollment commenced in March 2014, and data collection will continue for 10 years from enrolment of the 300th patient.

Up to February 28, 2023, 223 HoFH patients aged ≥18 years with postlomitapide data available were enrolled in the study, 78.9% of whom received lomitapide for ≥12 months and 25.6% for 5–9 years. Mean duration of exposure was 38.5 months (range: 0.3–118.1). Global mean dose was 13.0 mg/day (Europe: 17.4 mg/day), which was considerably lower than the doses used in the original trial (maximum dose: 40 or 60 mg).

Main results

  • At any time during follow-up, 68.6% of the patients had an LDL-c reduction ≥50% from baseline.
  • Of the 223 patients, 163 (73.1%) achieved LDL-c <100 mg/dL and 105 (47.1%) reached <70 mg/dL at any time after initiation of the lomitapide treatment.
  • In safety analysis, the most common events of special interest were hepatic events (18.8%), followed by MACE (17.0%) and gastrointestinal events (14.3%).
  • Abnormal liver function tests (ALT/AST ratio ≥3x the upper limit of normal (ULN) or bilirubin ≥2 ULN) were observed in 46 patients (20.6%), and 13 patients (5.8%) discontinued treatment due to liver enzyme increases.
  • Hepatic steatosis was observed in 6 patients at baseline, and a total of 10 patients were reported to have this liver condition at any time during follow-up.
  • Overall, 50 patients (22.4%) experienced adverse events leading to discontinuation of the study treatment, most of which were gastrointestinal events.


Real-world data from the global prospective LOWER registry over 9 years demonstrated the effectiveness of lomitapide treatment in 223 adult patients with HoFH, with ~75% of them achieving LDL-c <100 mg/dL and almost half reaching LDL-c <70 mg/dL. Safety analysis results were consistent with the known safety profile of lomitapide, and no new safety concerns were identified. Dr. Blom remarked that “what we really need at the moment is long-term follow-up especially with regard to hepatic safety and hepatic fibrosis in these patients.”

- Our reporting is based on the information provided at the EAS Congress 2024 -

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