Format

Send to

Choose Destination
J Clin Lipidol. 2018 Mar - Apr;12(2):390-396.e8. doi: 10.1016/j.jacl.2017.12.008. Epub 2017 Dec 28.

Alirocumab efficacy in patients with double heterozygous, compound heterozygous, or homozygous familial hypercholesterolemia.

Author information

1
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
2
Department of Clinical Genetics, Academic Medical Centre, Amsterdam, The Netherlands.
3
Lipid Clinic, Oslo University Hospital, Oslo, Norway.
4
School of Medicine, University of Utah, Salt Lake City, UT, USA.
5
Cardiovascular R&D, Sanofi, Montpellier, France.
6
Translational Medicine and Early Development, Sanofi, Frankfurt, Germany.
7
Translational Medicine, Regeneron Pharmaceuticals, Inc., New York, NY, USA.
8
Department of Molecular Medicine, 'Sapienza' University of Rome, Umberto I Hospital, Rome, Italy. Electronic address: claudia.stefanutti@uniroma1.it.

Abstract

BACKGROUND:

Mutations in the genes for the low-density lipoprotein receptor (LDLR), apolipoprotein B, and proprotein convertase subtilisin/kexin type 9 have been reported to cause heterozygous and homozygous familial hypercholesterolemia (FH).

OBJECTIVE:

The objective is to examine the influence of double heterozygous, compound heterozygous, or homozygous mutations underlying FH on the efficacy of alirocumab.

METHODS:

Patients from 6 alirocumab trials with elevated low-density lipoprotein cholesterol (LDL-C) and FH diagnosis were sequenced for mutations in the LDLR, apolipoprotein B, proprotein convertase subtilisin/kexin type 9, LDLR adaptor protein 1 (LDLRAP1), and signal-transducing adaptor protein 1 genes. The efficacy of alirocumab was examined in patients who had double heterozygous, compound heterozygous, or homozygous mutations.

RESULTS:

Of 1191 patients sequenced, 20 patients were double heterozygotes (n = 7), compound heterozygotes (n = 10), or homozygotes (n = 3). Mean baseline LDL-C levels were similar between patients treated with alirocumab (n = 11; 198 mg/dL) vs placebo (n = 9; 189 mg/dL). All patients treated with alirocumab 75/150 or 150 mg every 2 weeks had an LDL-C reduction of ≥15% at either week 12 or 24. At week 12, 1 patient had an increase of 7.1% in LDL-C, whereas in others, LDL-C was reduced by 21.7% to 63.9% (corresponding to 39-114 mg/dL absolute reduction from baseline). At week 24, LDL-C was reduced in all patients by 8.8% to 65.1% (10-165 mg/dL absolute reduction from baseline). Alirocumab was generally well tolerated in the 6 trials.

CONCLUSION:

Clinically meaningful LDL-C-lowering activity was observed in patients receiving alirocumab who were double heterozygous, compound heterozygous, or homozygous for genes that are causative for FH.

KEYWORDS:

APOB; Alirocumab; Hypercholesterolemia; LDLR; LDLRAP1

PMID:
29396260
DOI:
10.1016/j.jacl.2017.12.008
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center