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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 30, No 5, September/October 2019
AFRICA
279
Long-term safety and efficacy of alirocumab in
South African patients with heterozygous familial
hypercholesterolaemia: the ODYSSEY Open-Label
Extension study
Dirk J Blom, Johannes Breedt, Lesley J Burgess, Iftikhar O Ebrahim, Graham Ellis, Prashilla Soma,
Eugene van der Walt, Poobalan Naidoo, Alet van Tonder, Frederick J Raal
Abstract
Background:
Alirocumab reduces low-density lipoprotein
cholesterol (LDL-C) levels by up to 61%. The ODYSSEY
Open-Label Extension study investigated the effect of
alirocumab in patients with heterozygous familial hypercho-
lesterolaemia (HeFH) over 144 weeks.
Methods:
Eligible patients with HeFH had completed an
earlier double-blind, randomised, placebo-controlled parent
study. Patients were initiated on 75 mg alirocumab Q2W
subcutaneous (SC) unless baseline LDL-C was
>
8.9 mmol/l,
in which case they received 150 mg alirocumab Q2W. Dose
titration to 150 mg Q2W was at the investigator’s discretion.
Results:
The study enrolled 167 patients and the parent study
mean (
±
SD) baseline LDL-C level was 3.65
±
1.9 mmol/l.
Mean LDL-C level was reduced by 48.7% at week 144; mean
on-treatment LDL-C was 2.30
±
1.24 mmol/l. Eight patients
reported injection-site reactions, with one treatment discon-
tinuation. Treatment emergent anti-drug antibodies were
identified in five patients but these did not affect the efficacy.
Conclusion:
Alirocumab effectively and safely reduced LDL-C
in these patients.
Keywords:
alirocumab, PCSK9 inhibitors, familial hypercholes-
terolaemia, LDL-C goal, lipid-lowering therapy, cardiovascular
risk, statin
Submitted 11/3/19, accepted 21/6/19
Published online 11/9/19
Cardiovasc J Afr
2019;
30
: 279–284
www.cvja.co.zaDOI: 10.5830/CVJA-2019-039
Familial hypercholesterolaemia is a genetic disorder of lipid
metabolism characterised by low-density lipoprotein cholesterol
(LDL-C) hypercholesterolaemia, tendon xanthomata in some
but not all patients, and premature severe cardiovascular
disease.
1
Founder effects are seen in multiple ethnicities in
South Africa, including Afrikaners (one in 72),
2
the Ashkenazy
Jewish population of Lithuanian origin (one in 67),
3
and the
Indian population of Gujarati origin (more than one in 100).
4
Because heterozygous familial hypercholesterolaemia (HeFH) is
characterised by severe baseline LDL-C hypercholesterolaemia,
most patients are not able to reach LDL-C targets with current
lipid-modifying therapies.
5
Proprotein convertase/subtilisin kexin type 9 (PCSK9)
is an important regulator of LDL-C homeostasis. It is an
enzymatically inactive serine protease that is predominantly
secreted by the liver. Circulating PCSK9 binds to LDL receptors
on the hepatocyte surface. LDL receptors with bound PCSK9
are still internalised normally but cannot recycle to the cell
surface and are degraded in the hepatocyte. Reducing the
concentration of free PCSK9 reduces degradation of LDL
receptors and ultimately enhances LDL-C clearance due to the
increased number of LDL receptors available on the hepatocyte
cell surface.
6
Alirocumab is a subcutaneously administered (SC)
Department of Medicine, Division of Lipidology and Hatter
Institute for Cardiovascular Research in Africa, University
of Cape Town, Cape Town, South Africa
Dirk J Blom, MB ChB, MMed (Int Med), FCP (SA), PhD,
dirk.blom@uct.ac.zaEmmed Research, Pretoria West, South Africa
Johannes Breedt, MB ChB, DOH
Tread Research, Department of Cardiology, Faculty of
Medicine and Health Science, University of Stellenbosch,
Stellenbosch, South Africa
Lesley J Burgess, MB ChB, MMed, MSc, PGD (Int Res Ethics), PhD
Netcare Unitas Hospital, Centurion, South Africa
Iftikhar O Ebrahim, MB BCh, MMed (Int Med), Cert Cardiology (SA)
Synexus Helderberg Clinical Trial Centre, Somerset West,
South Africa
Graham Ellis, BSc Hons, MB ChB, MMed (Int Med)
Clinical Research Unit, Department of Clinical Research,
University of Pretoria, Pretoria, South Africa
Prashilla Soma, MB ChB, MSc (Clin Epi), PhD
Roodepoort Medicross Clinical Research Centre, Synexus
Affiliated Site, Roodepoort, South Africa
Eugene van der Walt, MB ChB, MBL
Sanofi, Johannesburg, South Africa
Poobalan Naidoo, BPharm (Hons), MB BCh, MMedSc
(Pharmacology)
Alet van Tonder, PhD
Carbohydrate and Lipid Metabolism Research Unit,
Faculty of Health Sciences, University of Witwatersrand,
Johannesburg, South Africa
Frederick J Raal, FRCP, FCP (SA), Cert Endo, MMed (Int Med),
PhD