Hiral Patel, PharmD. Candidate 2015, Mercer University College of Pharmacy
According to the US National Library of Medicine, the gene proprotein convertase subtilisin/kexin type 9 (PCSK9) appears to control the number of low-density lipoprotein (LDL) receptors which determines how quickly cholesterol is removed from the bloodstream.1
Alirocumab, a monoclonal antibody that inhibits PCSK9, has been shown to reduce LDL cholesterol levels in patients who are receiving statin therapy. In a phase two study, alirocumab in combination with atorvastatin for 12 weeks reduced LDL levels by 40 – 72%.2 However, longer term data on safety and efficacy of alirocumab are needed.
|Title: Efficacy and Safety of Alirocumab in Reducing Lipids and Cardiovascular Events 3|
|Design||Phase 3, randomized, double-blind, placebo-controlled, parallel-group, multinational study; 2,341 patients|
|Objective||To obtain longer-term data on reduction in LDL cholesterol levels|
|Study groups||Alirocumab vs. placebo|
|Methods||Patients were randomly assigned in a 2:1 ratio to receive alirocumab (150 mg) or placebo as a 1-ml subcutaneous injection every 2 weeks|
|Duration||78 weeks||Primary Outcome Measure||The mean percentage change in calculated LDL cholesterol level from baseline to week 24.|
|Baseline Characteristics||The mean age was 60 years and 37.8% were women. A total of 68.9% of patients had a history of coronary heart disease, and 17.7% had heterozygous familial hypercholesterolemia. The mean calculated LDL cholesterol level at baseline was 122 mg/dL.|
|Results||The mean percentage change in calculated LDL cholesterol level from baseline to week 24 was −61% with alirocumab (P<0.001).|
|Adverse Events||Common Adverse Events: Injection-site reactions (5.9%), myalgia (5.4%), amnesia (0.3%), memory impairment (0.3%), confused state (0.3%), ophthalmologic events (2.9%)|
|Serious Adverse Events: Death (0.3%), ischemic stroke (0.6%), ischemia driven coronary revascularization procedure (3.1%), congestive heart failure requiring hospitalization (0.6%)|
|Percentage that Discontinued due to Adverse Evens: 7.2%|
|Study Author Conclusions||Over a period of 78 weeks, alirocumab, when added to statin therapy at the maximum tolerated dose, significantly reduced LDL cholesterol levels.|
The results of this study suggest the addition of alirocumab to statin therapy significantly reduces LDL levels. However, there were a large number of patients that discontinued due to adverse events. Overall, this study shows the benefits of adding alirocumab to statin therapy in reducing LDL levels in high-risk patients.
1. Genetics Home Reference. PCSK9. Available at: http://ghr.nlm.nih.gov/gene/PCSK9. Accessed March 17, 2015.
2. Mckenney JM, Koren MJ, Kereiakes DJ, Hanotin C, Ferrand AC, Stein EA. Safety and efficacy of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease, SAR236553/REGN727, in patients with primary hypercholesterolemia receiving ongoing stable atorvastatin therapy. J Am Coll Cardiol. 2012;59(25):2344-53.
3. Robinson JG, Farnier M, Krempf M, et al. Efficacy and Safety of Alirocumab in Reducing Lipids and Cardiovascular Events. N Engl J Med. 2015.