The most common adverse events were injection-site reactions and headaches.
A specific dosing regimen of alirocumab could help patients with hypercholesterolemia reduce their low-density lipoprotein (LDL-C).
A team, led by Eli M. Roth, MD, FACCSterling Research Group, assessed the link between alirocumab, proprotein convertase subtilsin-kexin type 9 (PCSK9), and LDL-C concentrations with the CHOICE I alirocumab dosing regimen.
The trial, dubbed the ODYSSEY CHOICE I study, evaluated alirocumab 300 mg every 4 weeks in patients with hypercholesterolemia who received maximally tolerated statin or no statin.
Of the 803 patients included in the study, 547 were statin-treated and 256 were treated without a statin. Each patient was randomized to either alirocumab 300 mg every 4 weeks (Q4W), alirocumab 75 mg every 2 weeks, or placebo.
Both alirocumab dosing groups were adjusted to 150 mg every 2 weeks at week 12 if the week 8 LDL-C was >70 or >100 mg/dL, depending on cardiovascular risk, or if LDL-C reduction was <30% from baseline.
However, the majority of patients in the alirocumab 300 mg group remaining on the dosing schedule with adjustment as they achieved study-defined LDL-C goals at week 8 (statin-treated: 80.7%; no statin: 85.3%).
Overall, LDL-C was reduced by 60.5-71.9% over weeks 20-24 in the alirocumab 300 mg every 4 weeks group and 57.2-63.0% in patients with dose adjustments in this arm.
The investigators also found statin-treated patients had higher cardiovascular risks and higher free PCSK, as well as lower alirocumab concentrations when compared to the no statin group.
This suggests an increased target-mediated clearance in this patient group.
The most common adverse events regardless of statin status in the study-drug treated patients was injection-site reactions and headaches.
Overall, the researchers believe alirocumab 300 mg every 4 weeks is an optimal treatment for patients with hypercholesteremia.
“Data provide further insight on alirocumab’s mode of action in terms of relationship between alirocumab, PCSK9 and LDL-C, and disease severity, and support the use of alirocumab 300 mg Q4W as an efficacious dosing regimen for clinically meaningful LDL-C reductions,” the authors said.
In 2019, the US Food and Drug Administration (FDA) has accepted the supplemental Biologics License Application (sBLA) for alirocumab as a preventive therapy in overall major adverse cardiovascular event (MACE) risk.
The PCSK9 inhibitor from Sanofi and Regeneron Pharmaceuticals was the first of its drug class to be approved for the treatment of high LDL-cholesterol (LDL-C) in adjunction with diet and statin therapy, in June 2015.
The 2019 indication cleared it to help reduce patient risk of heart attack, ischemic stroke, fatal coronary heart disease, and hospitalization from unstable angina.
Alirocumab’s sBLA was supported by data to come from the phase 3 ODYSSEY OUTCOMES trial, an approximate 19,000-patient study assessing the therapy in patients with acute coronary syndrome (ACS) within 1-12 months prior to enrollment.
The results showed patients administered alirocumab had a 15% reduced risk (HR .85; 95% CI: .78-.93; P= .0003) in MACE over 4 years. Overall, MACE occurred in 9.5% (n= 903) of treated patients, versus 11.1% (1052) of those administered placebo.
The study, “Pharmacodynamic relationship between PCSK9, alirocumab, and LDL-C lowering in the ODYSSEY CHOICE I trial,” was published online by the Journal of Clinical Lipidology.