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Orphanet Journal of Rare Diseases

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Open Access 01-12-2018 | Research

Target achievement and cardiovascular event rates with Lomitapide in homozygous Familial Hypercholesterolaemia

Authors: Dirk J. Blom, Marina Cuchel, Miranda Ager, Helen Phillips

Published in: Orphanet Journal of Rare Diseases | Issue 1/2018

Abstract

Background

Homozygous familial hypercholesterolaemia (HoFH) is characterized by a markedly increased risk of premature cardiovascular (CV) events and cardiac death. Lomitapide reduces low-density lipoprotein cholesterol (LDL-C) levels; however, the probable impact on LDL-C goals and CV events is unknown.

Methods

We used data collected in the first 26 weeks of the lomitapide pivotal phase 3 study (NCT00730236) to evaluate achievement of European Atherosclerosis Society (EAS) LDL-C targets. We used publicly available data reporting major adverse CV events (MACE) rates from other cohorts of HoFH patients to compare event rates for an equivalent number of patient years of exposure (98) in the lomitapide extension trial (NCT00943306).

Results

Twenty-nine patients were included in the phase 3 study. During the first 26 weeks, 15 (51%) and eight (28%) reached LDL-C targets of 100 mg/dL and 70 mg/dL, respectively, at least once. Fourteen (74%) and 11 (58%) of the 19 patients who remained in the extension study after week 126 reached LDL-C targets of 100 mg/dL and 70 mg/dL at least once during the entire study period. Only two MACE were reported in the lomitapide trials (one cardiac death and one coronary artery bypass graft (CABG)) – equivalent to 1.7 events per 1000 patient months of treatment. MACE rates were 21.7, 9.5 and 1.8 per 1000 patient-months respectively in cohorts of HoFH patients pre- and post-mipomersen, and receiving evolocumab. On treatment LDL-C levels were 166, 331 and 286 mg/dL for lomitapide, mipomersen and evolocumab, respectively.

Conclusions

Approximately three quarters and half of patients who took lomitapide for at least 2 years reached LDL-C goals of 100 mg/dL and 70 mg/dL, respectively. There were fewer major CV events per 1000 patient months of treatment in patients taking lomitapide, mipomersen or evolocumab than reported in the mipomersen cohort prior to starting mipomersen. These results support the hypothesis that novel lipid-lowering therapies may reduce CV events in HoFH patients by lowering LDL-C further.

Trial registration

NCT00730236 (registered 8 Aug 2008) and NCT00943306 (registered 22 July 2009).

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Title: Target achievement and cardiovascular event rates with Lomitapide in homozygous Familial Hypercholesterolaemia
Authors: Dirk J. Blom
Marina Cuchel
Miranda Ager
Helen Phillips
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Orphanet Journal of Rare Diseases / Issue 1/2018
Electronic ISSN: 1750-1172
DOI: https://doi.org/10.1186/s13023-018-0841-3

At a glance: The STEP trials

Springer Medicine

Target achievement and cardiovascular event rates with Lomitapide in homozygous Familial Hypercholesterolaemia

Abstract

Background

Methods

Results

Conclusions

Trial registration

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Trial registration

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