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Praluent (alirocumab) - 4 indications
Scroll down for more information on each indication:
- for the treatment of adult patients with heterozygous familial hypercholesterolemia (HeFH) or patients with clinical atherosclerotic cardiovascular disease; Approved July 2015 and expanded March of 2024 to include patients >8 years of age with HeFH
- to reduce the risk of heart attack, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular (CV) disease; Approved April of 2019
- as add-on therapy for adult patients with homozygous familial hypercholesterolemia (HoFH); Approved April of 2021
General Information
Praluent (alirocumab) is a PCSK9 (proprotein convertase subtilisin kexin type 9) inhibitor antibody.
Praluent is specifically indicated:
- To reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease
- As an adjunct to diet, alone or in combination with other low density lipoprotein cholesterol (LDL-C)-lowering therapies, in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), to reduce LDL-C and as an adjunct to diet and other LDL-C-lowering therapies in pediatric patients aged 8 years and older with HeFH to reduce LDL-C
- As an adjunct to other LDL-C-lowering therapies in adult patients with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C
Praluent is supplied as an injection for subcutaneous administration. Assess LDL-C when clinically appropriate. The LDL-lowering effect of Praluent may be measured as early as 4 weeks after initiation. Administer Praluent subcutaneously into areas of the thigh, abdomen, or upper arm that are not tender, bruised, red, or indurated. Rotate injection sites for each administration.
Scroll down for specific dosing recommendations for each indication.
Mechanism of Action
Praluent (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. LDLR is the primary receptor that clears circulating LDL; therefore, the decrease in LDLR levels by PCSK9 results in higher blood levels of LDL-C. By inhibiting the binding of PCSK9 to LDLR, alirocumab increases the number of LDLRs available to clear LDL, thereby lowering LDL-C levels.
Side Effects
Adverse effects associated with the use of Praluent may include, but are not limited to, the following:
- Nasopharyngitis
- Injection site reactions
- Influenza
- Myalgia
Indication 1 and 2 - adults with HeFH or with clinical atherosclerotic cardiovascular disease and patients >8 years of age with HeFH
In adults with established cardiovascular disease or with primary hyperlipidemia, including HeFH :
- The recommended starting dosage of Praluent is either 75 mg once every 2 weeks or 300 mg once every 4 weeks administered subcutaneously.
- For patients receiving Praluent 300 mg every 4 weeks, measure LDL-C just prior to the next scheduled dosage, because LDL-C can vary between dosages in some patients.
- If the LDL-C response is inadequate, the dosage may be adjusted 150 mg subcutaneously every 2 weeks.
- In adults with HeFH undergoing LDL apheresis the recommended dosage of Praluent is 150 mg once every 2 weeks administered subcutaneously.
- Praluent can be administered without regard to the timing of LDL apheresis.
In pediatric patients with HeFH:
- The recommended dosage of Praluent for patients with a body weight less than 50 kg is 150 mg once every 4 weeks administered subcutaneously.
- The recommended dosage of Praluent for patients with a body weight of 50 kg or more is 300 mg once every 4 weeks administered subcutaneously.
- If the LDL-C response is inadequate, the dosage may be adjusted for patients with a body weight less than 50 kg to 75 mg subcutaneously once every 2 weeks or for patients with a body weight of 50 kg or more to 150 mg subcutaneously once every 2 weeks.
The FDA approval of Praluent was based on five double-blind placebo-controlled trials that enrolled 3,499 patients; 36 percent were patients with HeFH and 54 percent were non-FH patients who had clinical atherosclerotic cardiovascular disease. Three of the five trials were conducted exclusively in patients with HeFH. All patients were receiving a maximally tolerated dose of a statin, with or without other lipid-modifying therapies. All trials were at least 52 weeks in duration with the primary efficacy end point measured at week 24 (mean percentage change in LDL-C from baseline). Three studies used an initial dose of 75 mg every two weeks (Q2W) followed by criteria-based uptitration to 150 mg Q2W at week 12 for patients who did not achieve their predefined target LDL-C at week 8. The majority of patients (57 percent to 83 percent) who were treated for at least 12 weeks did not require up-titration. Two studies used a 150-mg Q2W dose.
Study 1 was a multicenter, double-blind, placebo-controlled trial that randomly assigned 1,553 patients to Praluent 150 mg Q2W and 788 patients to placebo. Overall, 69 percent were non-FH patients with clinical atherosclerotic cardiovascular disease and 18 percent had HeFH. The average LDL-C at baseline was 122 mg/dL. At week 24, the treatment difference between Praluent and placebo in mean LDL-C percent change was -58 percent.
Study 2 was a multicenter, double-blind, placebo-controlled trial that randomly assigned 209 patients to Praluent and 107 to placebo. Overall, 84 percent had clinical atherosclerotic cardiovascular disease. Mean baseline LDL-C was 102 mg/dL. At week 12, the mean percentage change from baseline in LDL-C was -45 percent with Praluent compared to 1 percent with placebo, and the treatment difference between Praluent 75mg Q2W and placebo in mean LDL-C percent change was -46 percent. At week 12, if additional LDL-C lowering was required based on prespecified LDL-C criteria, Praluent was up-titrated to 150 mg Q2W for the remainder of the trial. At week 24, the mean percentage change from baseline in LDL-C was -44 percent with Praluent and -2 percent with placebo, and the treatment difference between Praluent and placebo in mean LDL-C percentage change was -43 percent. The dose was up-titrated to 150 mg Q2W in 32 (17 percent) of 191 patients treated with Praluent for at least 12 weeks.
Studies 3 and 4 were multicenter, double-blind, placebo-controlled trials that, combined, randomly assigned 490 patients to Praluent and 245 to placebo. The trials were similar with regard to both design and eligibility criteria. All patients had HeFH, were taking a maximally tolerated dose of statin with or without other lipid-modifying therapy and required additional LDL-C reduction. Overall, 45 percent of these patients with HeFH also had clinical atherosclerotic cardiovascular disease. The average LDL-C at baseline was 141 mg/dL. At week 12, the treatment difference between Praluent 75 mg Q2W and placebo in mean LDL-C percent change was -48 percent. At week 12, if additional LDL-C lowering was required based on prespecified LDL-C criteria, Praluent was up-titrated to 150 mg Q2W for the remainder of the trials. At week 24, the mean treatment difference between Praluent and placebo in mean LDL-C percentage change from baseline was -54 percent. The dose was up-titrated to 150 mg Q2W in 196 (42 percent) of 469 patients treated with Praluent for at least 12 weeks. The LDL-C-lowering effect was sustained to week 52.
Study 5 was a multicenter, double-blind, placebo-controlled trial that randomly assigned 72 patients to Praluent 150 mg Q2W and 35 patients to placebo. Patients had HeFH with a baseline LDL-C ≥160 mg/dL while taking a maximally tolerated dose of statin with or without other lipid-modifying therapy. Overall, 50 percent had clinical atherosclerotic cardiovascular disease. The average LDL-C at baseline was 198 mg/dL. At week 24, the mean percentage change from baseline in LDL-C was -43 percent with Praluent and -7 percent with placebo, and the treatment difference between Praluent and placebo in mean LDL-C percentage change was -36 percent.
FDA approval for children over the age of 8 years with HeFH was based on a Phase 3, randomized multicenter trial evaluating pediatric patients aged 8 to 17 with HeFH, who had LDL-C levels of 130mg/dL or greater and were already being treated with lipid-lowering medications. Patients were randomized to receive Praluent (N=101) or placebo (N=52) every two or four weeks in two consecutive cohorts. Patients who received Praluent every four weeks had 31% lower LDL-C than placebo at 24 weeks. Improvements in additional key lipid parameters were also observed.
Indication 3 - to reduce the risk of heart attack, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular (CV) disease
Approved April of 2019
In adults with established cardiovascular disease
- The recommended starting dosage of Praluent is either 75 mg once every 2 weeks or 300 mg once every 4 weeks administered subcutaneously.
- For patients receiving Praluent 300 mg every 4 weeks, measure LDL-C just prior to the next scheduled dosage, because LDL-C can vary between dosages in some patients.
- If the LDL-C response is inadequate, the dosage may be adjusted 150 mg subcutaneously every 2 weeks.
The FDA approval of Praluent to reduce the risk of heart attack, stroke and unstable angina requiring hospitalization in adults with established cardiovascular (CV) disease was based on Odyssey Outcomes, assessing the effect of adding Praluent to maximally-tolerated statins on CV outcomes in 18,924 patients who had an acute coronary syndrome (ACS) within a year of enrolling in the trial. Patients who received Praluent in the trial experienced:
- A 15 percent reduced risk for major CV events. The primary end point included time to first heart attack, stroke, death from coronary heart disease (CHD), or unstable angina requiring hospitalization
- A 27 percent reduced risk of stroke, 14 percent reduced risk of non-fatal heart attack and 39 percent reduced risk of unstable angina requiring hospitalization.
- A 15 percent reduced risk of death from any cause (also called all-cause mortality) was also observed.
Indication 4 - as add-on therapy for adult patients with homozygous familial hypercholesterolemia (HoFH)
Approved April of 2021
In adults with HoFH the recommended dosage of Praluent is 150 mg once every 2 weeks administered subcutaneously.
FDA approval was based on a 12-week, double-blind, randomized trial among adult patients with HoFH. In the trial, 45 patients received 150 mg of Praluent every two weeks and 24 patients received a placebo. Patients were taking other therapies to lower LDL-C as well. The primary measure of effectiveness was the percent change in LDL-C from the beginning of treatment to week 12. At week 12, patients receiving Praluent had an average 27% decrease in LDL-C whereas patients on the placebo had an average 9% increase.