1. Shigle, Amanda Jo
  2. Sheridan, Dan RPh, MS

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One of my patients has been prescribed alirocumab, which is in a new class of antihyperlipidemic drugs known as PCSK9 inhibitors. What do I need to know about these drugs?-V.O., MINN.


Amanda Jo Shigle and Dan Sheridan, RPh, MS, reply: For decades, HMG-CoA reductase inhibitors (statins) have been the mainstay in the fight against low-density lipoprotein cholesterol (LDL-C). Lower LDL-C levels have been associated with a significant reduction of adverse cardiovascular (CV) events and marked reductions in risk for coronary heart disease (CHD).1 Although statins as an adjunct therapy to diet are considered the main treatment option, additional pharmacotherapy is sometimes warranted for patients at high risk for CHD and those with statin intolerance, statin-related adverse reactions, or inherited disorders of LDL-cholesterol metabolism. A new class of medications can help lower LDL-C in these cases.2-42-4


Alirocumab is a monoclonal antibody that targets proprotein convertase subtilisin kexin type 9 (PCSK9). PCSK9 inhibitors have emerged as powerful new cholesterol-lowering agents. These drugs increase the removal of LDL-C from circulation by stabilizing the receptors needed to eliminate LDL-C from the body.5 Research has shown that they consistently lower LDL-C by up to 60%, regardless of baseline levels.2 In July 2015, the FDA approved alirocumab as the first drug in this new class. A second drug, evolocumab, was approved in August 2015.6-86-8


Administered by subcutaneous injection, alirocumab and evolocumab were approved for use in addition to diet and maximally tolerated statin therapy in adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic CV disease, who require additional lowering of LDL-C cholesterol.6,76,7


Both PCSK9 inhibitors need to be refrigerated at 2[degrees] C to 8[degrees] C (36[degrees] F to 46[degrees] F) in the original carton to protect them from light. The medications are administered once every 2 weeks and are available in a device similar to an insulin pen, so administration takes 5 minutes or less.1,61,6 Patients or caregivers must be properly trained before they can administer these medications.


The projected cost of these medications-$7,000 to $12,000 annually-is a major barrier to their use.7 Generic statins, by contrast, cost around $50 a year. This large price difference could deter patients from using the more costly drugs.


During clinical trials, both alirocumab and evolocumab were well tolerated by patients. The most common adverse reactions included nasopharyngitis, upper respiratory tract infections, back pain, arthralgia, influenza, nausea, injection site reactions, and rash.6,9,106,9,106,9,10 These drugs were associated with a low incidence of skeletal muscle effects such as myopathy and rhabdomyolysis, raising hopes that the PCSK9 inhibitors can be substituted in patients who experience this statin-related adverse reaction. Presently, no safety concerns have been identified with the PCSK9 inhibitors, but postmarketing studies will be conducted to analyze potential harm.




1. NationalCholesterol Education Program (U.S.). Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (adult treatment panel III) Final Report. Circulation. 2002;106(25):3143-3421. [Context Link]


2. Hassan M, Yacoub M. GAUSS-2, RUTHERFORD-2, LAPLACE-2, DESCARTES, and TESLA Part B: PCSK9 inhibitors gain momentum. Glob Cardiol Sci Pract. 2014;2014(4):360-366. [Context Link]


3. Steinberg D, Witztum JL. Inhibition of PCSK9: a powerful weapon for achieving ideal LDL cholesterol levels. Proc Natl Acad Sci U S A. 2009;106(24):9546-9547.


4. Wierzbicki AS, Perera D, Ewang-Emukowhate M. Dyslipidaemia: What's around the corner. Clin Med. 2014;14(suppl 6):s41-s44. [Context Link]


5. Ling H, Burns TL, Hilleman DE. An update on the clinical development of proprotein convertase subtilisin kexin 9 inhibitors, novel therapeutic agents for lowering low-density lipoprotein cholesterol. Cardiovasc Ther. 2014;32(2):82-88. [Context Link]


6. FDA approves Praluent to treat certain patients with high cholesterol. FDA News Release. 2015. [Context Link]


7. FDA approves new cholesterol drug. American Heart Association News. 2015. [Context Link]


8. FDA approves Repatha to treat certain patients with high cholesterol. FDA News Release. 2015. [Context Link]


9. FDA Briefing Document. Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC). 2015. [Context Link]


10. Regeneron. Praluent (alirocumab) Injection: Highlights of Prescribing Information. 2015. [Context Link]