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Clinical data: Homozygous Familial

The following summarises the key clinical data supporting Lojuxta in HoFH. Links are also available to the scientific publications on PubMed of these data below under Publications. If you would like further information, please contact Medical Information on medinfo@amrytpharma.com.

The approval for Lojuxta® (lomitapide) is based on a multi-national, single arm, open label Phase III study which evaluated the safety and efficacy of lomitapide to reduce LDL-C levels in 29 adult patients with HoFH and was published in the Lancet in 2013.

When added to the existing lipid-lowering therapy of statins, ezetimibe and apheresis (in 63% patients) lomitapide significantly reduced LDL-C by mean 40% (ITT population) and by mean 50% in the 23 patients who completed the study through Week 26. After Week 26, the patients entered a safety phase lasting 52 weeks, and average reductions in LDL-C were sustained.

During this safety phase of the study, patients were able to stop apheresis, at the clinician’s discretion and six of the 13 patients on apheresis either stopped apheresis completely (n=3) or reduced the frequency of apheresis (n=3). In addition, 16 subjects (55%) achieved the critical LDL-C target levels as defined by the European Atherosclerosis Society of < 2.5 mmol/L (< 100mg/dl) for adult patients with HoFH and of these 9 patients (31%) achieved levels < 1.8 mmol/L (< 70mg/dl) for adult patients with HoFH and atherosclerotic cardiovascular disease (ACVD) at any time throughout the study. At entry to the study, none of the 29 patients were able to achieve these levels on maximal tolerated lipid lowering therapies, with or without apheresis.

Consistent with its mechanism of action of preventing the absorption of fats from the diet, the most common adverse reactions in the study were gastrointestinal, reported by 27 (93%) of 29 patients. Also consistent with its mechanism of action of preventing the production of VLDL and LDL-C in the liver, elevations in liver enzymes and hepatic fat were observed in the Phase III study. 10 of the 29 patients in the study had at least one elevation in liver enzymes ≥ three times the upper limit of normal (3x ULN), including four patients who experienced liver enzymes ≥ 5x ULN. Liver enzyme elevations were managed through dose reduction or temporary discontinuation of dose. Hepatic fat increased from a baseline of 1% to a median absolute increase of 6% at 26 and 78 weeks.

See the Summary of Product Characteristics for further information.

Long-term extension study

Following the 78-week pivotal Phase III study, 19 eligible patients entered the long-term extension study and continued on lomitapide at the individualised doses established in the Phase III pivotal study (published in Circulation, Blom et al 2017). Overall, 17 of the 19 patients (89%) who enrolled in the long-term extension study completed at least 126 weeks of treatment and the median lomitapide treatment duration was 5.1 years (range, 2.1–5.7 years). The mean LDL-C reduction was 45.5%, consistent with that observed in the pivotal Phase III study. LDL-C of ≤100mg/dL and ≤70mg/dL was achieved at any time from baseline by 13 (68%) and nine (47%) patients, respectively. The adverse event profile in patients who continued on the long-term extension study was similar to that observed in the pivotal Phase III study and no new safety signals were identified.

Real-world evidence

There are several publications that report data in case reports and / or cohort analyses following treatment with lomitapide in the ‘real world’. The largest patient cohort study published by Erasmo et al (Advances in Therapeutics 2017) is a retrospective analysis of 15 adult patients with a genetically confirmed diagnosis of HoFH receiving treatment with lomitapide for up to three years. Prior to receiving lomitapide, their median LDL-C level was 426.0 mg/dL or 11 mmol/L – despite receiving treatment with statins, ezetimibe and apheresis (in 10 of the 15 patients). The addition of lomitapide (average daily dosage of 19 mg/day) lowered LDL-C levels a mean 68.2 ± 24.8% versus baseline and by 76.5 ± 16.7% at lowest value prior to changes in apheresis schedules. At their last visit, 60% of patients showed LDL-C <100 mg/dL and 46.6% <70 mg/dL. During treatment with lomitapide, eight of the 10 patients receiving LA (80%) stopped this treatment due to the pronounced cholesterol reduction. In addition, two remaining patients on apheresis reduced their apheresis requirements by 40%. During follow-up, 53.3% of patients reported at least one episode of diarrhoea, but none was severe; none had persistent liver transaminase >5 X ULN or had to stop treatment due to side effects.

Registry data

In addition to the real-world evidence, there is data from the global Lomitapide Observational Worldwide Evaluation Registry (LOWER), a post-marketing requirement to study the long-term safety, effectiveness and patterns of use in patients treated with lomitapide globally. The occurrence and outcomes of pregnancies is evaluated through a separate pregnancy-exposure registry [PER].

The registry is non-interventional, with no provided study medications and no required procedures. The Registry will enrol at least 300 adult HoFH patients who will be followed for a minimum of 10 years, in the EU patients will be followed indefinitely. The inclusion criteria include patients at least 18 years old and who commenced therapy with lomitapide 0–15 months prior to enrolment. The exclusion criteria include those receiving lomitapide in a clinical trial or receiving an investigational agent. The Registry is currently enrolling in US, Europe and Canada.


This is a list of the key publications in Homozygous Familial Hypercholesterolaemia (HoFH) and Lojuxta (lomitapide) capsules in the management of HoFH. Included are links to the papers on PubMed. If you would like further information, please contact Medical Information on medinfo@amrytpharma.com.

Author Title
Cuchel et al. (2014) Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society
Bruckert E. Kalmykova O, Bittar R et al. (2017) Long-term outcome in 53 patients with homozygous familial hypercholesterolaemia in a single centre in France
Thompson G, Seed M, Naoumova R et al. Improved cardiovascular outcomes following temporal advances in lipid-lowering therapy in a genetically-characterised cohort of familial hypercholesterolaemia homozygotes

Papers on efficacy and safety of lomitapide

Author Title
José Real et al. (2018) Rare disease - Management of homozygous familial hypercholesterolaemia in two brothers
Cuchel M, Meagher EA, du Toit Theron H, et al. Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, Phase III study
Blom D, Averna M, Meagher E et al. (2017) Long-Term Efficacy and Safety of the Microsomal Triglyceride Transfer Protein Inhibitor Lomitapide in Patients With Homozygous Familial Hypercholesterolemia
Roeters Van Lennep J. Averna M, Alonso R. Treating homozygous familial hypercholesterolemia in a real-world setting: Experiences with lomitapide
Stefanutti C, Morozzi C, Di Giacomo S. Management of homozygous familial hypercholesterolaemia in real-world clinical practice: a report of seven Italian patients treated in Rome with lomitapide and lipoprotein apheresis
DeGoma E. Lomitapide for the Management of Homozygous Familial Hypercholesterolemia
D’Erasmo, A.B. Cefalu, D. Noto et al. Efficacy of lomitapide in the treatment of familial homozygous hypercholesterolemia: results of a real world clinical experience in Italy
Blom DJ., Fahad ZA., Kastelein JP et al. LOWER, a registry of lomitapide-treated patients with homozygous familial hypercholesterolemia: Rationale and design
Leipold R, Raal FJ, Ishak J, et al. Potential efficacy of lomitapide, a MTP (microsomal triglyceride transfer protein) inhibitor, on survival in homozygous familial hypercholesterolaemia (HoFH) – results of an event modelling analysis

Papers on treatment algorithms in HoFH

Author Title
France M, Rees A, Data D et al. HEART UK statement on the management of homozygous familial hypercholesterolaemia in the United Kingdom
Stefanutti et al. Towards an international consensus – integrating lipoprotein apheresis and new lipid-lowering drugs