Pharmacological Class:
Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor.

Active Ingredient(s):
Alirocumab 75mg/mL, 150mg/mL; per prefilled pen or syringe; soln for SC inj; preservative-free.

Company
Sanofi and Regeneron
Indication(s):
Adjunct to diet and maximally tolerated statin therapy, in adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic ­cardiovascular disease requiring additional lowering of LDL-C. Limitations of use: effect on cardiovascular morbidity and mortality has not been determined.

Pharmacology:
Alirocumab is a human monoclonal antibody that binds to PCSK9. PCSK9 binds to the low-density lipoprotein receptors (LDLR) on the surface of hepatocytes to promote LDLR degradation within the liver. By inhibiting the binding of PCSK9 to LDLR, alirocumab increases the number of LDLRs available to clear LDL, thereby lowering LDL-C levels.

Clinical Trials:
The efficacy of Praluent was studied in 5 double-blind, placebo-controlled trials that enrolled 3,499 patients; 3 of the 5 trials were exclusively studied in patients with heterozygous familial hypercholesterolemia. All patients were receiving a maximally tolerated dose of a statin, with or without other lipid-modifying therapies.

Three studies used an initial dose of 75mg every 2 weeks followed by criteria-based up-titration to 150mg every 2 weeks at Week 12 for those who did not meet their pre-defined target LDL-C at Week 8; two studies only used a dose of 150mg every 2 weeks.

Study 1 randomized 1,553 patients to Praluent 150mg every 2 weeks and 788 patients to placebo. At Week 24, the treatment difference between Praluent and placebo in mean LDL-C percent change was −58% (95% CI: −61%, −56%; P<0.0001).

Study 2 randomized 209 patients to Praluent and 107 to placebo. At Week 24, the mean percent change from baseline in LDL-C was −44% with Praluent and −2% with placebo. The treatment difference between Praluent and placebo in mean LDL-C percent change was −43% (95% CI: −50%, −35%; P<0.0001). The dose was up-titrated to 150mg every 2 weeks in 32 patients treated with Praluent for at least 12 weeks.

Studies 3 and 4 randomized a total of 490 patients to Praluent and 245 to placebo. At Week 12, the treatment difference between Praluent 75mg every 2 weeks and placebo in mean LDL-C percent change was −48% (95% CI: −52%, −44%). At Week 24, the mean treatment difference between Praluent and placebo in mean LDL-C percent change from baseline was −54% (95% CI: −59%, −50%; P<0.0001). The dose was up-titrated to 150mg every 2 weeks in 196 patients treated with Praluent for at least 12 weeks. The LDL-C lowering effect was sustained to Week 52.

Study 5 randomized 72 patients to Praluent 150mg every 2 weeks and 35 patients to placebo. At Week 24, the mean percent change from baseline in LDL-C was −43% with Praluent and −7% with placebo. The treatment difference between Praluent and placebo in mean LDL-C percent change was −36% (95% CI: −49%, −24%; P<0.0001).

For more clinical trial data, see full labeling.

Legal Classification:
Rx

Adults:
Give by SC injection into thigh, abdomen, or upper arm; rotate injection sites. Initially 75mg once every 2 weeks; if inadequate LDL-C response, may increase to max 150mg given every 2 weeks. Measure LDL-C levels within 4–8 weeks of initiation or titration; adjust dose if needed.

Children:
Not established.

Warnings/Precautions:
Do not inject into areas of active skin disease or injury (eg, sunburns, rashes, inflammation, skin infections). Discontinue if serious allergic reactions occur. Pregnancy (2nd & 3rd trimesters). Nursing mothers.

Interaction(s)
Avoid co-administration with other injectable drugs at same injection site.

Adverse Reaction(s)
Nasopharyngitis, injection site reactions (eg, erythema/redness, itching, swelling, pain/tenderness), influenza.

How Supplied:
Single-dose prefilled pen or syringe (1mL)—1, 2

LAST UPDATED:
8/18/2015