A new class of lipid-lowering drugs hits the market
In late July, the first PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, alirocumab (Praluent—Sanofi-Aventis, Regeneron), received FDA approval as an adjunct to diet and maximally tolerated statin therapy for adult patients with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who require additional cholesterol lowering (i.e., LDL lowering). Alirocumab is a monoclonal antibody that is self-administered by patients via subcutaneous injection once every 2 weeks.
This novel drug works by inhibiting PCSK9, which is responsible for reducing the number of receptors on the liver that remove LDL from the bloodstream. Therefore, blocking of PCSK9 by alirocumab results in a higher number of LDL receptors that are available to clear LDL. Data from clinical trials have demonstrated significant LDL lowering when alirocumab is used in combination with statins, but the effects on cardiovascular morbidity and mortality remain to be determined.
The approval of alirocumab was based on a large global clinical trial program known as ODYSSEY. This program included numerous clinical trials and its approval was based on results from five key studies which included approximately 3,500 patients. Across the five trials, significant reductions in LDL levels were observed with use of alirocumab in addition to standard of care (i.e., statins) compared with placebo plus standard of care. The mean LDL percent change at week 24 between alirocumab and placebo ranged from −36% to −58% across the five studies. The most commonly reported adverse reactions were nasopharyngitis, injection site reactions, and influenza.
Currently, a trial evaluating the effects of alirocumab on cardiovascular risk reduction is ongoing (ODYSSEY OUTCOMES), but a post-hoc analysis of the ODYSSEY LONG TERM trial did show that the rate of major cardiovascular events was lower with alirocumab compared with placebo. Specifically, the rate of the composite of death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization was 1.7% with alirocumab compared with 3.3% with placebo (hazard ratio 0.52 [95% CI 0.31–0.90, P = 0.02).
Since alirocumab is a self-administered subcutaneous injection, patients and/or caregivers should be educated on proper use. The medication must be taken out of the refrigerator and allowed to warm to room temperature for 30 to 40 minutes before use, but should be used as soon as possible after it has warmed up and within 24 hours.
Educate patients on proper aseptic technique and how to use the prefilled pen or prefilled syringe correctly. Inform them that the drug can be injected into the thigh, abdomen, or upper arm, and that it may take up to 20 seconds to inject the full dose. Injection sites should be rotated and patients should be told to avoid injecting the drug into areas of active skin disease, such as sunburns, skin rashes, or skin infections. In addition, alirocumab should not be coadministered into areas where other injections have been given.
Patients also should be aware of the potential for allergic reactions to occur. Instruct them to stop therapy and seek prompt medical attention if any signs or symptoms of a serious allergic reaction occur. Educate patients on the most common type of adverse reactions that have been reported such as injection-site reactions that include redness, itching, swelling, or pain/tenderness at the injection site.
Patients should be educated on proper storage, administration, and potential adverse reactions. Patients should be aware of the potential for allergic reactions to occur and be aware of the need to seek medical treatment immediately for severe reactions.
Manufacturer: Sanofi-Aventis, Regeneron
Drug class: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor
Indication: For use as an adjunct to diet and maximally tolerated statin therapy for adult patients with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who require additional lowering of their LDL levels.
Dosage: 75 mg administered subcutaneously once every 2 weeks, with an increase to 150 mg given once every 2 weeks if patients fail to reach LDL goals at the lower starting dose.
- LDL levels should be assessed within 4 to 8 weeks of initiating or titrating the dose of alirocumab to determine response.
- For missed injections, patients may administer the dose if within 7 days of the missed dose; if greater than 7 days has passed, patients should wait until the next scheduled dose.
Of note: Alirocumab is contraindicated in patients with a history of a serious hypersensitivity reaction to the drug.
- The potential for allergic reactions (e.g., pruritus, rash, urticaria) to occur is listed under the warnings and precautions section of the label.