Efficacy and Safety of Alirocumab in Reducing Lipids and Cardiovascular Events

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.

References:
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.

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s