The lipid-lowering effects of lomitapide are unaffected by adjunctive apheresis in patients with homozygous familial hypercholesterolaemia - a post-hoc analysis of a Phase 3, single-arm, open-label trial

C Stefanutti; D J Blom; M R Averna; E A Meagher; H dT Theron; A D Marais; R A Hegele; C R Sirtori; P K Shah; D Gaudet; G B Vigna; B S Sachais; S Di Giacomo; A M E du Plessis; L T Bloedon; J Balser; D J Rader; M Cuchel; Phase 3 HoFH Lomitapide Study Investigators

doi:10.1016/j.atherosclerosis.2015.03.014

The lipid-lowering effects of lomitapide are unaffected by adjunctive apheresis in patients with homozygous familial hypercholesterolaemia - a post-hoc analysis of a Phase 3, single-arm, open-label trial

Atherosclerosis. 2015 Jun;240(2):408-14. doi: 10.1016/j.atherosclerosis.2015.03.014. Epub 2015 Mar 14.

Authors

C Stefanutti¹, D J Blom², M R Averna³, E A Meagher⁴, H dT Theron⁵, A D Marais², R A Hegele⁶, C R Sirtori⁷, P K Shah⁸, D Gaudet⁹, G B Vigna¹⁰, B S Sachais⁴, S Di Giacomo¹, A M E du Plessis¹¹, L T Bloedon¹², J Balser¹³, D J Rader⁴, M Cuchel¹⁴; Phase 3 HoFH Lomitapide Study Investigators

Affiliations

¹ 'Sapienza' University of Rome, Rome, Italy.
² University of Cape Town, Cape Town, South Africa.
³ Università di Palermo, Palermo, Italy.
⁴ University of Pennsylvania, Philadelphia, PA, USA.
⁵ Netcare Private Hospital, Bloemfontein, South Africa.
⁶ Robarts Research Institute and University of Western Ontario, London, ON, Canada.
⁷ Ospedale Niguarda, Milano, Italy.
⁸ Cedars-Sinai Heart Institute, Los Angeles, CA, USA.
⁹ Université de Montreal, Chicoutimi, Canada.
¹⁰ Università di Ferrara, Ferrara, Italy.
¹¹ University of Pretoria, South Africa.
¹² Aegerion Pharmaceuticals, Cambridge, MA, USA.
¹³ Veristat, Holliston, MA, USA.
¹⁴ University of Pennsylvania, Philadelphia, PA, USA. Electronic address: mcuchel@mail.med.upenn.edu.

PMID: 25897792
PMCID: PMC4573555
DOI: 10.1016/j.atherosclerosis.2015.03.014

Abstract

Objective: Lomitapide (a microsomal triglyceride transfer protein inhibitor) is an adjunctive treatment for homozygous familial hypercholesterolaemia (HoFH), a rare genetic condition characterised by elevated low-density lipoprotein-cholesterol (LDL-C), and premature, severe, accelerated atherosclerosis. Standard of care for HoFH includes lipid-lowering drugs and lipoprotein apheresis. We conducted a post-hoc analysis using data from a Phase 3 study to assess whether concomitant apheresis affected the lipid-lowering efficacy of lomitapide.

Methods: Existing lipid-lowering therapy, including apheresis, was to remain stable from Week -6 to Week 26. Lomitapide dose was escalated on the basis of individual safety/tolerability from 5 mg to 60 mg a day (maximum). The primary endpoint was mean percent change in LDL-C from baseline to Week 26 (efficacy phase), after which patients remained on lomitapide through Week 78 for safety assessment and further evaluation of efficacy. During this latter period, apheresis could be adjusted. We analysed the impact of apheresis on LDL-C reductions in patients receiving lomitapide.

Results: Of the 29 patients that entered the efficacy phase, 18 (62%) were receiving apheresis at baseline. Twenty-three patients (13 receiving apheresis) completed the Week 26 evaluation. Of the six patients who discontinued in the first 26 weeks, five were receiving apheresis. There were no significant differences in percent change from baseline of LDL-C at Week 26 in patients treated (-48%) and not treated (-55%) with apheresis (p = 0.545). Changes in Lp(a) levels were modest and not different between groups (p = 0.436).

Conclusion: The LDL-C lowering efficacy of lomitapide is unaffected by lipoprotein apheresis.

Trial registration: ClinicalTrials.gov NCT00730236.

Keywords: Homozygous familial hypercholesterolaemia; Lipoprotein apheresis; Lomitapide.

Publication types

Clinical Trial, Phase III
Multicenter Study
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adult
Anticholesteremic Agents / administration & dosage*
Anticholesteremic Agents / adverse effects
Benzimidazoles / administration & dosage*
Benzimidazoles / adverse effects
Biomarkers / blood
Blood Component Removal / adverse effects
Blood Component Removal / methods*
Cholesterol, LDL / blood*
Combined Modality Therapy
Female
Genetic Predisposition to Disease
Homozygote*
Humans
Hyperlipoproteinemia Type II / blood
Hyperlipoproteinemia Type II / diagnosis
Hyperlipoproteinemia Type II / genetics
Hyperlipoproteinemia Type II / therapy*
Lipoprotein(a) / blood
Male
Phenotype
Time Factors
Treatment Outcome
Young Adult

Substances

Anticholesteremic Agents
BMS201038
Benzimidazoles
Biomarkers
Cholesterol, LDL
Lipoprotein(a)

Associated data

ClinicalTrials.gov/NCT00730236

Grants and funding

UL1 RR024134/RR/NCRR NIH HHS/United States