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283
received ezetimibe treatment.
13
In the South African cohort,
statin treatment was reported by 143 (85.6%) and ezetimibe
treatment by 46 (27.5%) patients. It is not clear how many
patients were on combination LMT.
Higher reductions in LDL-C would have been expected if
more participants were up-titrated to the maximum dose of
alirocumab. A total of 76 patients (54% of the SA cohort)
remained on treatment with 75 mg of alirocumab Q2W for the
duration of the study, even though up-titration of the dose was
allowed at the investigator’s discretion.
A greater LDL-C reduction of 61% was reported in the
ODYSSEY Long-Term study at week 24.
9
However, all the
participants in the active arm of the ODYSSEY Long-Term
study received the maximum dose of alirocumab (150 mg every
two weeks), as opposed to only 46% of participants receiving the
maximum dose of alirocumab in ODYSSEY OLE.
In South Africa the diagnosis of HeFH is based mainly on
clinical criteria as per the Simon Broome criteria.
11
or the Dutch
Lipid Network criteria with a score
>
8.
12
Genetic testing is rarely
performed due to cost.
According to the 2017 European Society of Cardiology/
European Atherosclerosis Society guidelines for the use of
PCKS9i, HeFH patients should be considered for treatment
with PCSK9i in two scenarios: patients on treatment with
maximum tolerated doses of statins and/or ezetimibe where
LDL-C remains
>
4.5 mmol/l, or where additional risk factors
are present and LDL-C remains
>
3.6 mmol/l.
14
In the present study, treatment-emergent anti-drug antibodies
were identified in five patients during the study but were reported
to be non-neutralising. Indeed, sustained LDL-C reduction was
observed in all patients over the 144-week study period.
Drug-neutralising anti-drug antibodies were induced by
treatment with bococizumab, a humanised antibody containing
approximately 3% murine sequence, resulting in attenuated
LDL-C reduction.
15
Alirocumab is, however, a fully humanised
PCSK9 inhibitor. A review of 10 alirocumab studies has shown
that while anti-drug antibodies were observed in approximately
5.1% of patients receiving the active treatment, LDL-C reduction
was not attenuated.
16
Additionaladverseeffectsobservedinthestudywerecomparable
to those reported in previous studies with alirocumab,
8-10,13
and
included injection-site reactions and athralgia. The safety results
must be interpreted with caution as the sample size was relatively
small, and rare adverse events may not have been detected.
Nevertheless, the safety profile of alirocumab, especially related to
muscle symptoms, was favourable. This is especially relevant give
that statin-associated muscle symptoms and statin intolerance
may limit adherence to statins.
17
An advantage of the ODYSSEY OLE study is that the data
collected partially represent real-world evidence of the safety
and efficacy of alirocumab: during the study alirocumab was
self-administered by patients, LMT and alirocumab doses were
adjusted at the investigator’s discretion, and study visits were
fewer than in previous studies in the ODYSSEY programme.
Conclusion
Results from the South African cohort enrolled in the ODYSSEY
OLE study confirm that alirocumab was safe, efficacious and
well tolerated in the South African HeFH patients.
All authors were investigators in the study. Sanofi was the sponsor of the
study. AvT and PN are employees of Sanofi. Neither AvT nor PN owns stocks
in Sanofi. DB has received clinical trial fees, and honoraria for advisory board
participation and for speaking from Sanofi. FR has received research grants,
honoraria or consulting fees for professional input and/or delivered lectures
from Sanofi, Regeneron, Amgen and The Medicines Company.
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