These Highlights Do Not Include All The Information Needed To Use Praluent Safely And Effectively. See Full Prescribing Information For Praluent.

Adverse Reactions in Adults with Hypercholesterolemia

The data in Table 1 are derived from 9 primary hypercholesterolemia placebo-controlled trials that included 2,476 adult patients treated with PRALUENT 75 mg and/or 150 mg every 2 weeks, including 2,135 exposed for 6 months and 1,999 exposed for more than 1 year (median treatment duration of 65 weeks). The mean age of the population was 59 years, 40% of the population were female, 90% were White, 4% were Black or African American, 3% were Asian, and 3% other races; 6% identified as Hispanic or Latino ethnicity.

Adverse reactions reported in at least 2% of PRALUENT-treated patients, and more frequently than in placebo-treated patients, are shown in Table 1.

Adverse reactions led to discontinuation of treatment in 5.3% of patients treated with PRALUENT and 5.1% of patients treated with placebo. The most common adverse reactions leading to treatment discontinuation in patients treated with PRALUENT were allergic reactions (0.6% versus 0.2% for PRALUENT and placebo, respectively) and elevated liver enzymes (0.3% versus <0.1%).

In an analysis of ezetimibe-controlled trials in which 864 patients were exposed to PRALUENT for a median of 27 weeks and 618 patients were exposed to ezetimibe for a median of 24 weeks, the types and frequencies of common adverse reactions were similar to those listed above.

Store in a refrigerator at 36°F to 46°F (2°C to 8°C) in the original carton to protect from light.

Do not freeze. Do not shake.

PRALUENT may be kept at room temperature up to 77°F (25°C) in the original carton for 30 days. If not used within the 30 days, discard PRALUENT.

Alirocumab is a human monoclonal antibody (IgG1 isotype) that targets proprotein convertase subtilisin kexin type 9 (PCSK9). Alirocumab is a PCSK9 inhibitor produced by recombinant DNA technology in Chinese Hamster Ovary cell suspension culture. Alirocumab consists of two disulfide-linked human heavy chains, each covalently linked through a disulfide bond to a human kappa light chain. A single N-linked glycosylation site is located in each heavy chain within the CH2 domain of the Fc constant region of the molecule. The variable domains of the heavy and light chains combine to form the PCSK9 binding site within the antibody. Alirocumab has an approximate molecular weight of 146 kDa.

PRALUENT is a sterile, preservative-free, clear, colorless to pale yellow solution for subcutaneous use. PRALUENT 75 mg/mL or 150 mg/mL solution for subcutaneous injection in a single-dose pre-filled pen is supplied in a siliconized 1 mL Type-1 clear glass syringe.

Each 75 mg/mL pre-filled pen contains 75 mg alirocumab, histidine (8 mM), polysorbate 20 (0.1 mg), sucrose (100 mg), and Water for Injection USP, to pH 6.0.

Each 150 mg/mL pre-filled pen contains 150 mg alirocumab, histidine (6 mM), polysorbate 20 (0.1 mg), sucrose (100 mg), and Water for Injection USP, to pH 6.0.

If a dose is missed:

• Within 7 days from the missed dose, instruct the patient to administer PRALUENT and resume the patient's original schedule.
• More than 7 days after the missed dose:
  • For every 2-week dosage, instruct the patient to wait until the next dose on the original schedule.
  • For every 4-week dosage, instruct the patient to administer the dose and start a new schedule based on this date.

The safety and effectiveness of PRALUENT as an adjunct to diet and other LDL-C-lowering therapies for the treatment of HeFH have been established in pediatric patients aged 8 years and older. Use of PRALUENT for this indication is based on data from a 24-week, randomized, placebo-controlled, double-blind trial in pediatric patients with HeFH. In the trial, 101 patients received PRALUENT and 52 patients received placebo; 26 patients (17%) were 8 to 9 years of age. This indication is supported by evidence from controlled trials in adults [see Adverse Reactions (6.1) and Clinical Studies (14.3)].

The safety and effectiveness of PRALUENT have not been established in pediatric patients with HeFH who are younger than 8 years of age or in pediatric patients with other types of hypercholesterolemia.

In controlled trials, 3663 patients treated with PRALUENT were ≥65 years of age and 734 patients treated with PRALUENT were ≥75 years of age. No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the trials described below with the incidence of anti-drug antibodies in other trials, including those of PRALUENT or of other alirocumab products.

In adult patients with CV disease (Trial 1), the incidence of anti-alirocumab antibody (ADA) formation was 5.5% (504/9,091) in patients treated with PRALUENT 75 mg and/or 150 mg every 2 weeks for up to 5 years (with a median treatment exposure of 31 months). Neutralizing antibody (NAb) responses were observed in 0.5% (43/9,091) of all patients treated with PRALUENT. Of the patients who developed ADA, 8.5% (43/504) tested positive for NAb.

• While reductions in LDL-C were generally comparable in patients with or without ADA, including NAbs, some adult patients treated with PRALUENT with persistent or neutralizing antibodies experienced attenuation in LDL-C efficacy.
• Adult patients who developed ADA had a higher incidence of injection site reactions compared to patients without ADA (7.5% vs 3.6%) [see Adverse Reactions (6.1)].

In a pool of placebo-controlled and active-controlled trials of adult patients treated with PRALUENT 75 mg and/or 150 mg every 2 weeks as well as in a separate clinical trial of patients treated with PRALUENT 75 mg every 2 weeks or 300 mg every 4 weeks (including some patients with dose adjustment to 150 mg every 2 weeks), during the treatment period ranging from 6 to 24 months, the incidence of detecting ADA was 4.8% (147/3,033) and NAb was 1.2% (36/3,033), which was similar to the results from the trial described above.

In pediatric patients aged 8 to 17 years with HeFH (Trial 12), the incidence of ADA for patients treated with PRALUENT was 3% (3/98) with a median treatment exposure of 24 weeks in patients receiving PRALUENT once every 2 weeks and 23 weeks in patients receiving PRALUENT once every 4 weeks with an optional up-titration. Of the 3 pediatric patients who developed ADA, no one tested positive for NAb.

Because of the low occurrence of ADA and the small number of pediatric patients enrolled, the effect of these antibodies on the pharmacokinetics, pharmacodynamics, safety, and/or effectiveness of PRALUENT in pediatric patients is unknown.

PRALUENT is contraindicated in patients with a history of a serious hypersensitivity reaction to alirocumab or any of the excipients in PRALUENT. Hypersensitivity vasculitis, angioedema, and hypersensitivity reactions requiring hospitalization have occurred [see Warnings and Precautions (5.1)].

The following adverse reactions are also discussed in the other sections of the labeling:

• Hypersensitivity Reactions [see Warnings and Precautions (5.1)]

No dose adjustment is needed for patients with mild or moderately impaired renal function. No data are available in patients with severe renal impairment [see Clinical Pharmacology (12.3)].

PRALUENT ^® (PRAHL-u-ent)

(alirocumab)

Injection, for Subcutaneous Injection

Single-Dose Pre-Filled Pen (75 mg/mL)

Keep this leaflet. If you have questions, ask your healthcare provider or call 1-844-PRALUENT (1-844-772-5836).

The parts of the PRALUENT pen are shown in this picture.

Step A: Getting ready for your injection.

Before you start you will need:

• the PRALUENT pen
• 1 alcohol wipe
• 1 cotton ball or gauze
• a sharps container or a puncture-resistant container (see Step B8)

A1: Look at the label on the pen.

• Check that you have the correct product and the correct dose.
• Check the expiration date (EXP): do not use if this date has passed.

A2: Look at the window.

• Check the liquid is clear, colorless to pale yellow and free from particles (see Figure A).
• You may see air bubbles. This is normal.
• Do not use if the window appears solid yellow (see Figure B).
• Do not use this medicine if the solution is discolored or cloudy, or if it contains visible flakes or particles.

A3: Let the pen warm up at room temperature for 30 to 40 minutes.

• This is important for administering the entire dose and helps minimize discomfort.
• Take PRALUENT out of the refrigerator to warm up before using.
• Do not heat the pen, let it warm up on its own.
• Do not put the pen back in the refrigerator.

A4: Prepare the injection site.

• Wash your hands with soap and water and dry with a towel.
• Clean skin in the injection area with an alcohol wipe.
• You can inject into your (see picture):
  • thighs
  • stomach (except for the 2 inch area around your belly button)
  • upper arms
• You can stand or sit to give yourself an injection.

Important:

• Change (rotate) your injection site each time you give yourself an injection. If you need to use the same injection site, make sure it is not the same spot on the site you used last time.
• Do not inject into areas where the skin is tender, bruised, hard, or red. Do not inject PRALUENT into areas with visible veins, scars or stretch marks.

Step B: How to give your injection.

B1: After completing all steps in "Step A: Getting ready for your injection", pull off the blue cap.

• Do not pull off the cap until you are ready to inject.
• Do not put the blue cap back on.

B2: Hold the PRALUENT pen like this.

• Do not touch the yellow safety cover.
• Make sure you can see the window.

B3: Press the yellow safety cover on your skin at roughly a 90° angle.

• For children younger than 12 years of age, pinching the skin before and during the injection is required.
• In adults and children aged 12 years and older, pinching of skin may be required to make the injection site firm.
• Press and firmly hold the pen against your body until the yellow safety cover is no longer visible. The pen will not work if the yellow safety cover is not depressed fully.

B4: Push and immediately release the green button with your thumb.

• You will hear a click. Your injection has now started.
• The window will start to turn yellow.

B5: Keep holding the pen against your skin after releasing the button.

• The injection may take up to 20 seconds.

B6: Check the window has turned yellow, before removing the pen.

• Do not remove the pen until the entire window has turned yellow.
• Your injection is complete when the window has turned completely yellow, you may hear a second click.
• If the window does not turn completely yellow, call 1-844-772-5836 for help. Do not give yourself a second dose without speaking to your healthcare provider.

B7: Pull pen away from your skin.

• Do not rub the skin after the injection.
• If you see any blood, press a cotton ball or gauze on the site until the bleeding stops.

B8: Throw away (Discard) pen and cap.

• Do not put the blue cap back on.
• Throw away pen and cap in a puncture-resistant container immediately after they have been used.

Disposing of used pens:

• Put your used pens in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) pens and caps in your household trash.
• If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:
  • made of a heavy-duty plastic,
  • can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
  • upright and stable during use,
  • leak-resistant, and
  • properly labeled to warn of hazardous waste inside the container.
• When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.
• Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.

Keep PRALUENT and all medicines out of the reach of children.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Manufactured by:

sanofi-aventis U.S. LLC

Bridgewater, NJ 08807

A SANOFI COMPANY

U.S. License # 1752

Marketed by: sanofi-aventis U.S. LLC (Bridgewater, NJ 08807)

and Regeneron Pharmaceuticals, Inc. (Tarrytown, NY 10591)

PRALUENT is a registered trademark of Sanofi

©2024 Regeneron Pharmaceuticals, Inc. / sanofi-aventis U.S. LLC

Revised: March 2024

Alirocumab reduced free PCSK9 in a concentration-dependent manner. Following a single subcutaneous administration of alirocumab 75 or 150 mg, maximal suppression of free PCSK9 occurred within 4 to 8 hours. Free PCSK9 concentrations returned to baseline when alirocumab concentrations decreased below the limit of quantitation.

No dose adjustment is needed for patients with mild or moderate hepatic impairment. No data are available in patients with severe hepatic impairment [see Clinical Pharmacology (12.3)].

PRALUENT^® is indicated:

• To reduce the risk of major adverse cardiovascular (CV) events (coronary heart disease death, myocardial infarction, stroke, or unstable angina requiring hospitalization) in adults at increased risk for these events.
• As an adjunct to diet and exercise to reduce low- density lipoprotein cholesterol (LDL-C) in:
  • adults with hypercholesterolemia.
  • adults and pediatric patients aged 8 years and older with heterozygous familial hypercholesterolemia (HeFH).
  • adults with homozygous familial hypercholesterolemia (HoFH).

Alirocumab is a human monoclonal antibody that binds to proprotein convertase subtilisin kexin type 9 (PCSK9). PCSK9 binds to the low-density lipoprotein (LDL) 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.

Hypersensitivity reactions: hypersensitivity vasculitis, angioedema, and other hypersensitivity reactions requiring hospitalization, have been reported with PRALUENT treatment. If signs or symptoms of serious hypersensitivity reactions occur, discontinue treatment with PRALUENT, treat according to the standard of care, and monitor until signs and symptoms resolve. (5.1)

• In adults with hypercholesterolemia, including HeFH (2.1):
  • 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 or in adults with HoFH (2.1):
  • 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 (2.2):
  • 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.
• Assess LDL-C when clinically appropriate. The LDL-lowering effect of PRALUENT may be measured as early as 4 weeks after initiation. (2.1)
• 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. (2.4)
• To administer the 300 mg dosage, give two 150 mg PRALUENT injections consecutively at two different injection sites. (2.4)

PRALUENT injection is a clear, colorless to pale yellow solution available as follows:

• 75 mg/mL single-dose pre-filled pen
• 150 mg/mL single-dose pre-filled pen

The following adverse reactions have been reported during post-approval use of PRALUENT. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• Hypersensitivity reactions: Angioedema
• Influenza-like illness

Hypersensitivity reactions, including hypersensitivity vasculitis, angioedema, and other hypersensitivity reactions requiring hospitalization, have been reported with PRALUENT treatment. If signs or symptoms of serious hypersensitivity reactions occur, discontinue treatment with PRALUENT, treat according to the standard of care, and monitor until signs and symptoms resolve. PRALUENT is contraindicated in patients with a history of a serious hypersensitivity reaction to alirocumab or any excipient in PRALUENT [see Contraindications (4)].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

• Hypercholesterolemia, 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 [see Dosage and Administration (2.4)].
  • For patients receiving PRALUENT 300 mg every 4 weeks, measure LDL-C just prior to the next scheduled dose, because LDL-C can vary between doses in some patients [see Clinical Studies (14)].
  • If the LDL-C response is inadequate, the dosage may be adjusted to 150 mg subcutaneously every 2 weeks.
• HeFH undergoing LDL apheresis or with HoFH:
  • The recommended dosage of PRALUENT is 150 mg once every 2 weeks administered subcutaneously [see Dosage and Administration (2.4)].
  • PRALUENT can be administered without regard to the timing of LDL apheresis.
  • Assess LDL-C when clinically appropriate. The LDL-lowering effect of PRALUENT may be measured as early as 4 weeks after initiation.

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

PRALUENT injection is a clear, colorless to pale yellow solution, supplied as follows:

The needle shield is not made with natural rubber latex.

• Train patients and/or caregivers on how to prepare and administer PRALUENT, according to the Instructions for Use and instruct them to read and follow the Instructions for Use each time they use PRALUENT.
• In children aged 12 to 17 years, it is recommended that PRALUENT be given by or under the supervision of an adult. In children aged 8 to 11 years, PRALUENT should be given by a caregiver.
• Prior to use, allow PRALUENT to warm to room temperature for 30 to 40 minutes if PRALUENT has been refrigerated [see How Supplied/Storage and Handling (16)].
• Visually inspect PRALUENT prior to administration. PRALUENT is a clear, colorless to pale yellow solution. Do not use if the solution is cloudy, discolored, or contains particles.
• 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. It may take up to 20 seconds to inject PRALUENT.
• To administer the 300 mg dose, give two 150 mg PRALUENT injections consecutively at two different injection sites.

During a 13-week toxicology study of 75 mg/kg once weekly alirocumab in combination with 40 mg/kg once daily atorvastatin in adult monkeys, there were no effects of PRALUENT on the humoral immune response to keyhole limpet hemocyanin (KLH) after one to two months at exposures 100-fold greater than the exposure at the maximum recommended human dose of 150 mg every two weeks, based on AUC.

NDC 0024-5901-01

Rx ONLY

Praluent^®

alirocumab

Injection

75 mg/mL

One Pre-filled Pen

For subcutaneous injection only. Single-dose.

Carton contains: One single-dose pre-filled pen, the Package Insert,

Patient Information, and Instructions for Use.

75 mg/mL

↓

OPEN

HERE

REGENERON

SANOFI

NDC 0024-5902-01

Rx ONLY

Praluent^®

alirocumab

Injection

150 mg/mL

One Pre-filled Pen

For subcutaneous injection only. Single-dose.

Carton contains: One single-dose pre-filled pen, the Package Insert,

Patient Information, and Instructions for Use.

150 mg/mL

↓

OPEN

HERE

REGENERON

SANOFI

NDC 0024-5904-01

Rx ONLY

Praluent^®

alirocumab

Injection

150 mg/mL

One Pre-filled Syringe

For subcutaneous injection only. Single-dose.

Carton contains: One single-dose pre-filled syringe,

the Package Insert, Patient Information, and Instructions for Use.

150 mg/mL

▶ OPEN

REGENERON

SANOFI

NDC 0024-5903-01

Rx ONLY

Praluent^®

alirocumab

Injection

75 mg/mL

One Pre-filled Syringe

For subcutaneous injection only. Single-dose.

Carton contains: One single-dose pre-filled syringe,

the Package Insert, Patient Information, and Instructions for Use.

75 mg/mL

▶ OPEN

REGENERON

SANOFI

Trial 12 (EFC14643, NCT03510884) was a randomized, multicenter, placebo controlled, double blind, 24 week trial in 153 pediatric patients aged 8 to 17 years with HeFH. Patients were on a low-fat diet and receiving background lipid-lowering therapy.

Patients were randomized in a 2:1 ratio to receive PRALUENT or placebo. In the PRALUENT group dosed every 2 weeks, 49 patients received a dose of 40 mg for body weight less than 50 kg or 75 mg for body weight 50 kg or more. The 40 mg dosage every 2 weeks is not approved [see Dosage and Administration (2.2)]. In the PRALUENT group dosed every 4 weeks, 52 patients received a dose of 150 mg for body weight less than 50 kg or 300 mg for body weight 50 kg or more. Dose adjustment of PRALUENT to 75 mg every 2 weeks for body weight less than 50 kg or 150 mg every 2 weeks for body weight 50 kg or more occurred at week 12 in patients with LDL-C ≥110 mg/dL.

Carcinogenicity studies have not been conducted with alirocumab. The mutagenic potential of alirocumab has not been evaluated; however, monoclonal antibodies are not expected to alter DNA or chromosomes.

There were no adverse effects on surrogate markers of fertility (e.g., estrous cyclicity, testicular volume, ejaculate volume, sperm motility, or total sperm count per ejaculate) in a 6-month chronic toxicology study in sexually-mature monkeys subcutaneously administered at 5, 15, and 75 mg/kg/week at systemic exposures up to 103-fold the 150 mg every two weeks subcutaneous clinical dose based on serum AUC. In addition, there were no adverse alirocumab-related anatomic pathology or histopathology findings in reproductive tissues in rat or monkey toxicology studies at systemic exposures up to 11-fold and 103-fold respectively, in the 6-month studies, compared to clinical systemic exposure following a 150 mg every two weeks dose, based on serum AUC.

• The recommended dosage of PRALUENT for patients with a body weight less than 50 kg is 150 mg once every 4 weeks administered subcutaneously [see Dosage and Administration (2.4)].
  • If the LDL-C lowering response is inadequate, the dosage may be adjusted to 75 mg subcutaneously once every 2 weeks [see Dosage and Administration (2.4)].
• 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 [see Dosage and Administration (2.4)].
  • If the LDL-C lowering response is inadequate, the dosage may be adjusted to 150 mg subcutaneously once every 2 weeks [see Dosage and Administration (2.4)].
• Assess LDL-C when clinically appropriate. The LDL-lowering effect of PRALUENT may be measured as early as 4 weeks after initiation.

Trial 1 (ODYSSEY OUTCOMES, NTC01663402) was a multicenter, double-blind, placebo-controlled trial in 18,924 adult patients (9,462 PRALUENT; 9,462 placebo) followed for up to 5 years. Patients had an acute coronary syndrome (ACS) event 4 to 52 weeks prior to randomization and were treated with a lipid-modifying therapy (LMT) regimen that was statin-intensive (defined as atorvastatin 40 or 80 mg, or rosuvastatin 20 or 40 mg) or at maximally tolerated dose of a statin, with or without other LMT. Patients were randomized to receive either PRALUENT 75 mg or placebo once every two weeks.

At month 2, if additional LDL-C lowering was required based on pre-specified LDL-C criteria (LDL-C ≥50 mg/dL), PRALUENT was adjusted to 150 mg every 2 weeks. For patients who had their dose adjusted to 150 mg every 2 weeks and who had two consecutive LDL-C values below 25 mg/dL, down-titration from 150 mg every 2 weeks to 75 mg every 2 weeks was performed. Patients on 75 mg every 2 weeks who had two consecutive LDL-C values below 15 mg/dL were switched to placebo in a blinded fashion. Approximately 2,615 (27.7%) of 9,451 patients treated with PRALUENT required dose adjustment to 150 mg every 2 weeks. Of these 2,615 patients, 805 (30.8%) were down-titrated to 75 mg every 2 weeks. Overall, 730 (7.7%) of 9,451 patients switched to placebo.

A total of 99.5% of patients were followed for survival until the end of the trial. The median follow-up duration was 33 months.

Adverse Reactions in Adults with Hypercholesterolemia

The data in Table 1 are derived from 9 primary hypercholesterolemia placebo-controlled trials that included 2,476 adult patients treated with PRALUENT 75 mg and/or 150 mg every 2 weeks, including 2,135 exposed for 6 months and 1,999 exposed for more than 1 year (median treatment duration of 65 weeks). The mean age of the population was 59 years, 40% of the population were female, 90% were White, 4% were Black or African American, 3% were Asian, and 3% other races; 6% identified as Hispanic or Latino ethnicity.

Adverse reactions reported in at least 2% of PRALUENT-treated patients, and more frequently than in placebo-treated patients, are shown in Table 1.

Adverse reactions led to discontinuation of treatment in 5.3% of patients treated with PRALUENT and 5.1% of patients treated with placebo. The most common adverse reactions leading to treatment discontinuation in patients treated with PRALUENT were allergic reactions (0.6% versus 0.2% for PRALUENT and placebo, respectively) and elevated liver enzymes (0.3% versus <0.1%).

In an analysis of ezetimibe-controlled trials in which 864 patients were exposed to PRALUENT for a median of 27 weeks and 618 patients were exposed to ezetimibe for a median of 24 weeks, the types and frequencies of common adverse reactions were similar to those listed above.

Store in a refrigerator at 36°F to 46°F (2°C to 8°C) in the original carton to protect from light.

Do not freeze. Do not shake.

PRALUENT may be kept at room temperature up to 77°F (25°C) in the original carton for 30 days. If not used within the 30 days, discard PRALUENT.

Alirocumab is a human monoclonal antibody (IgG1 isotype) that targets proprotein convertase subtilisin kexin type 9 (PCSK9). Alirocumab is a PCSK9 inhibitor produced by recombinant DNA technology in Chinese Hamster Ovary cell suspension culture. Alirocumab consists of two disulfide-linked human heavy chains, each covalently linked through a disulfide bond to a human kappa light chain. A single N-linked glycosylation site is located in each heavy chain within the CH2 domain of the Fc constant region of the molecule. The variable domains of the heavy and light chains combine to form the PCSK9 binding site within the antibody. Alirocumab has an approximate molecular weight of 146 kDa.

PRALUENT is a sterile, preservative-free, clear, colorless to pale yellow solution for subcutaneous use. PRALUENT 75 mg/mL or 150 mg/mL solution for subcutaneous injection in a single-dose pre-filled pen is supplied in a siliconized 1 mL Type-1 clear glass syringe.

Each 75 mg/mL pre-filled pen contains 75 mg alirocumab, histidine (8 mM), polysorbate 20 (0.1 mg), sucrose (100 mg), and Water for Injection USP, to pH 6.0.

Each 150 mg/mL pre-filled pen contains 150 mg alirocumab, histidine (6 mM), polysorbate 20 (0.1 mg), sucrose (100 mg), and Water for Injection USP, to pH 6.0.

If a dose is missed:

• Within 7 days from the missed dose, instruct the patient to administer PRALUENT and resume the patient's original schedule.
• More than 7 days after the missed dose:
  • For every 2-week dosage, instruct the patient to wait until the next dose on the original schedule.
  • For every 4-week dosage, instruct the patient to administer the dose and start a new schedule based on this date.

The safety and effectiveness of PRALUENT as an adjunct to diet and other LDL-C-lowering therapies for the treatment of HeFH have been established in pediatric patients aged 8 years and older. Use of PRALUENT for this indication is based on data from a 24-week, randomized, placebo-controlled, double-blind trial in pediatric patients with HeFH. In the trial, 101 patients received PRALUENT and 52 patients received placebo; 26 patients (17%) were 8 to 9 years of age. This indication is supported by evidence from controlled trials in adults [see Adverse Reactions (6.1) and Clinical Studies (14.3)].

The safety and effectiveness of PRALUENT have not been established in pediatric patients with HeFH who are younger than 8 years of age or in pediatric patients with other types of hypercholesterolemia.

In controlled trials, 3663 patients treated with PRALUENT were ≥65 years of age and 734 patients treated with PRALUENT were ≥75 years of age. No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the trials described below with the incidence of anti-drug antibodies in other trials, including those of PRALUENT or of other alirocumab products.

In adult patients with CV disease (Trial 1), the incidence of anti-alirocumab antibody (ADA) formation was 5.5% (504/9,091) in patients treated with PRALUENT 75 mg and/or 150 mg every 2 weeks for up to 5 years (with a median treatment exposure of 31 months). Neutralizing antibody (NAb) responses were observed in 0.5% (43/9,091) of all patients treated with PRALUENT. Of the patients who developed ADA, 8.5% (43/504) tested positive for NAb.

• While reductions in LDL-C were generally comparable in patients with or without ADA, including NAbs, some adult patients treated with PRALUENT with persistent or neutralizing antibodies experienced attenuation in LDL-C efficacy.
• Adult patients who developed ADA had a higher incidence of injection site reactions compared to patients without ADA (7.5% vs 3.6%) [see Adverse Reactions (6.1)].

In a pool of placebo-controlled and active-controlled trials of adult patients treated with PRALUENT 75 mg and/or 150 mg every 2 weeks as well as in a separate clinical trial of patients treated with PRALUENT 75 mg every 2 weeks or 300 mg every 4 weeks (including some patients with dose adjustment to 150 mg every 2 weeks), during the treatment period ranging from 6 to 24 months, the incidence of detecting ADA was 4.8% (147/3,033) and NAb was 1.2% (36/3,033), which was similar to the results from the trial described above.

In pediatric patients aged 8 to 17 years with HeFH (Trial 12), the incidence of ADA for patients treated with PRALUENT was 3% (3/98) with a median treatment exposure of 24 weeks in patients receiving PRALUENT once every 2 weeks and 23 weeks in patients receiving PRALUENT once every 4 weeks with an optional up-titration. Of the 3 pediatric patients who developed ADA, no one tested positive for NAb.

Because of the low occurrence of ADA and the small number of pediatric patients enrolled, the effect of these antibodies on the pharmacokinetics, pharmacodynamics, safety, and/or effectiveness of PRALUENT in pediatric patients is unknown.

PRALUENT is contraindicated in patients with a history of a serious hypersensitivity reaction to alirocumab or any of the excipients in PRALUENT. Hypersensitivity vasculitis, angioedema, and hypersensitivity reactions requiring hospitalization have occurred [see Warnings and Precautions (5.1)].

The following adverse reactions are also discussed in the other sections of the labeling:

• Hypersensitivity Reactions [see Warnings and Precautions (5.1)]

No dose adjustment is needed for patients with mild or moderately impaired renal function. No data are available in patients with severe renal impairment [see Clinical Pharmacology (12.3)].

PRALUENT ^® (PRAHL-u-ent)

(alirocumab)

Injection, for Subcutaneous Injection

Single-Dose Pre-Filled Pen (75 mg/mL)

Keep this leaflet. If you have questions, ask your healthcare provider or call 1-844-PRALUENT (1-844-772-5836).

The parts of the PRALUENT pen are shown in this picture.

Step A: Getting ready for your injection.

Before you start you will need:

• the PRALUENT pen
• 1 alcohol wipe
• 1 cotton ball or gauze
• a sharps container or a puncture-resistant container (see Step B8)

A1: Look at the label on the pen.

• Check that you have the correct product and the correct dose.
• Check the expiration date (EXP): do not use if this date has passed.

A2: Look at the window.

• Check the liquid is clear, colorless to pale yellow and free from particles (see Figure A).
• You may see air bubbles. This is normal.
• Do not use if the window appears solid yellow (see Figure B).
• Do not use this medicine if the solution is discolored or cloudy, or if it contains visible flakes or particles.

A3: Let the pen warm up at room temperature for 30 to 40 minutes.

• This is important for administering the entire dose and helps minimize discomfort.
• Take PRALUENT out of the refrigerator to warm up before using.
• Do not heat the pen, let it warm up on its own.
• Do not put the pen back in the refrigerator.

A4: Prepare the injection site.

• Wash your hands with soap and water and dry with a towel.
• Clean skin in the injection area with an alcohol wipe.
• You can inject into your (see picture):
  • thighs
  • stomach (except for the 2 inch area around your belly button)
  • upper arms
• You can stand or sit to give yourself an injection.

Important:

• Change (rotate) your injection site each time you give yourself an injection. If you need to use the same injection site, make sure it is not the same spot on the site you used last time.
• Do not inject into areas where the skin is tender, bruised, hard, or red. Do not inject PRALUENT into areas with visible veins, scars or stretch marks.

Step B: How to give your injection.

B1: After completing all steps in "Step A: Getting ready for your injection", pull off the blue cap.

• Do not pull off the cap until you are ready to inject.
• Do not put the blue cap back on.

B2: Hold the PRALUENT pen like this.

• Do not touch the yellow safety cover.
• Make sure you can see the window.

B3: Press the yellow safety cover on your skin at roughly a 90° angle.

• For children younger than 12 years of age, pinching the skin before and during the injection is required.
• In adults and children aged 12 years and older, pinching of skin may be required to make the injection site firm.
• Press and firmly hold the pen against your body until the yellow safety cover is no longer visible. The pen will not work if the yellow safety cover is not depressed fully.

B4: Push and immediately release the green button with your thumb.

• You will hear a click. Your injection has now started.
• The window will start to turn yellow.

B5: Keep holding the pen against your skin after releasing the button.

• The injection may take up to 20 seconds.

B6: Check the window has turned yellow, before removing the pen.

• Do not remove the pen until the entire window has turned yellow.
• Your injection is complete when the window has turned completely yellow, you may hear a second click.
• If the window does not turn completely yellow, call 1-844-772-5836 for help. Do not give yourself a second dose without speaking to your healthcare provider.

B7: Pull pen away from your skin.

• Do not rub the skin after the injection.
• If you see any blood, press a cotton ball or gauze on the site until the bleeding stops.

B8: Throw away (Discard) pen and cap.

• Do not put the blue cap back on.
• Throw away pen and cap in a puncture-resistant container immediately after they have been used.

Disposing of used pens:

• Put your used pens in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) pens and caps in your household trash.
• If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:
  • made of a heavy-duty plastic,
  • can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
  • upright and stable during use,
  • leak-resistant, and
  • properly labeled to warn of hazardous waste inside the container.
• When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.
• Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.

Keep PRALUENT and all medicines out of the reach of children.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Manufactured by:

sanofi-aventis U.S. LLC

Bridgewater, NJ 08807

A SANOFI COMPANY

U.S. License # 1752

Marketed by: sanofi-aventis U.S. LLC (Bridgewater, NJ 08807)

and Regeneron Pharmaceuticals, Inc. (Tarrytown, NY 10591)

PRALUENT is a registered trademark of Sanofi

©2024 Regeneron Pharmaceuticals, Inc. / sanofi-aventis U.S. LLC

Revised: March 2024

Alirocumab reduced free PCSK9 in a concentration-dependent manner. Following a single subcutaneous administration of alirocumab 75 or 150 mg, maximal suppression of free PCSK9 occurred within 4 to 8 hours. Free PCSK9 concentrations returned to baseline when alirocumab concentrations decreased below the limit of quantitation.

No dose adjustment is needed for patients with mild or moderate hepatic impairment. No data are available in patients with severe hepatic impairment [see Clinical Pharmacology (12.3)].

PRALUENT^® is indicated:

• To reduce the risk of major adverse cardiovascular (CV) events (coronary heart disease death, myocardial infarction, stroke, or unstable angina requiring hospitalization) in adults at increased risk for these events.
• As an adjunct to diet and exercise to reduce low- density lipoprotein cholesterol (LDL-C) in:
  • adults with hypercholesterolemia.
  • adults and pediatric patients aged 8 years and older with heterozygous familial hypercholesterolemia (HeFH).
  • adults with homozygous familial hypercholesterolemia (HoFH).

Alirocumab is a human monoclonal antibody that binds to proprotein convertase subtilisin kexin type 9 (PCSK9). PCSK9 binds to the low-density lipoprotein (LDL) 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.

Hypersensitivity reactions: hypersensitivity vasculitis, angioedema, and other hypersensitivity reactions requiring hospitalization, have been reported with PRALUENT treatment. If signs or symptoms of serious hypersensitivity reactions occur, discontinue treatment with PRALUENT, treat according to the standard of care, and monitor until signs and symptoms resolve. (5.1)

• In adults with hypercholesterolemia, including HeFH (2.1):
  • 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 or in adults with HoFH (2.1):
  • 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 (2.2):
  • 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.
• Assess LDL-C when clinically appropriate. The LDL-lowering effect of PRALUENT may be measured as early as 4 weeks after initiation. (2.1)
• 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. (2.4)
• To administer the 300 mg dosage, give two 150 mg PRALUENT injections consecutively at two different injection sites. (2.4)

PRALUENT injection is a clear, colorless to pale yellow solution available as follows:

• 75 mg/mL single-dose pre-filled pen
• 150 mg/mL single-dose pre-filled pen

The following adverse reactions have been reported during post-approval use of PRALUENT. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• Hypersensitivity reactions: Angioedema
• Influenza-like illness

Hypersensitivity reactions, including hypersensitivity vasculitis, angioedema, and other hypersensitivity reactions requiring hospitalization, have been reported with PRALUENT treatment. If signs or symptoms of serious hypersensitivity reactions occur, discontinue treatment with PRALUENT, treat according to the standard of care, and monitor until signs and symptoms resolve. PRALUENT is contraindicated in patients with a history of a serious hypersensitivity reaction to alirocumab or any excipient in PRALUENT [see Contraindications (4)].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

• Hypercholesterolemia, 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 [see Dosage and Administration (2.4)].
  • For patients receiving PRALUENT 300 mg every 4 weeks, measure LDL-C just prior to the next scheduled dose, because LDL-C can vary between doses in some patients [see Clinical Studies (14)].
  • If the LDL-C response is inadequate, the dosage may be adjusted to 150 mg subcutaneously every 2 weeks.
• HeFH undergoing LDL apheresis or with HoFH:
  • The recommended dosage of PRALUENT is 150 mg once every 2 weeks administered subcutaneously [see Dosage and Administration (2.4)].
  • PRALUENT can be administered without regard to the timing of LDL apheresis.
  • Assess LDL-C when clinically appropriate. The LDL-lowering effect of PRALUENT may be measured as early as 4 weeks after initiation.

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

PRALUENT injection is a clear, colorless to pale yellow solution, supplied as follows:

The needle shield is not made with natural rubber latex.

• Train patients and/or caregivers on how to prepare and administer PRALUENT, according to the Instructions for Use and instruct them to read and follow the Instructions for Use each time they use PRALUENT.
• In children aged 12 to 17 years, it is recommended that PRALUENT be given by or under the supervision of an adult. In children aged 8 to 11 years, PRALUENT should be given by a caregiver.
• Prior to use, allow PRALUENT to warm to room temperature for 30 to 40 minutes if PRALUENT has been refrigerated [see How Supplied/Storage and Handling (16)].
• Visually inspect PRALUENT prior to administration. PRALUENT is a clear, colorless to pale yellow solution. Do not use if the solution is cloudy, discolored, or contains particles.
• 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. It may take up to 20 seconds to inject PRALUENT.
• To administer the 300 mg dose, give two 150 mg PRALUENT injections consecutively at two different injection sites.

During a 13-week toxicology study of 75 mg/kg once weekly alirocumab in combination with 40 mg/kg once daily atorvastatin in adult monkeys, there were no effects of PRALUENT on the humoral immune response to keyhole limpet hemocyanin (KLH) after one to two months at exposures 100-fold greater than the exposure at the maximum recommended human dose of 150 mg every two weeks, based on AUC.

NDC 0024-5901-01

Rx ONLY

Praluent^®

alirocumab

Injection

75 mg/mL

One Pre-filled Pen

For subcutaneous injection only. Single-dose.

Carton contains: One single-dose pre-filled pen, the Package Insert,

Patient Information, and Instructions for Use.

75 mg/mL

↓

OPEN

HERE

REGENERON

SANOFI

NDC 0024-5902-01

Rx ONLY

Praluent^®

alirocumab

Injection

150 mg/mL

One Pre-filled Pen

For subcutaneous injection only. Single-dose.

Carton contains: One single-dose pre-filled pen, the Package Insert,

Patient Information, and Instructions for Use.

150 mg/mL

↓

OPEN

HERE

REGENERON

SANOFI

NDC 0024-5904-01

Rx ONLY

Praluent^®

alirocumab

Injection

150 mg/mL

One Pre-filled Syringe

For subcutaneous injection only. Single-dose.

Carton contains: One single-dose pre-filled syringe,

the Package Insert, Patient Information, and Instructions for Use.

150 mg/mL

▶ OPEN

REGENERON

SANOFI

NDC 0024-5903-01

Rx ONLY

Praluent^®

alirocumab

Injection

75 mg/mL

One Pre-filled Syringe

For subcutaneous injection only. Single-dose.

Carton contains: One single-dose pre-filled syringe,

the Package Insert, Patient Information, and Instructions for Use.

75 mg/mL

▶ OPEN

REGENERON

SANOFI

Trial 12 (EFC14643, NCT03510884) was a randomized, multicenter, placebo controlled, double blind, 24 week trial in 153 pediatric patients aged 8 to 17 years with HeFH. Patients were on a low-fat diet and receiving background lipid-lowering therapy.

Patients were randomized in a 2:1 ratio to receive PRALUENT or placebo. In the PRALUENT group dosed every 2 weeks, 49 patients received a dose of 40 mg for body weight less than 50 kg or 75 mg for body weight 50 kg or more. The 40 mg dosage every 2 weeks is not approved [see Dosage and Administration (2.2)]. In the PRALUENT group dosed every 4 weeks, 52 patients received a dose of 150 mg for body weight less than 50 kg or 300 mg for body weight 50 kg or more. Dose adjustment of PRALUENT to 75 mg every 2 weeks for body weight less than 50 kg or 150 mg every 2 weeks for body weight 50 kg or more occurred at week 12 in patients with LDL-C ≥110 mg/dL.

Carcinogenicity studies have not been conducted with alirocumab. The mutagenic potential of alirocumab has not been evaluated; however, monoclonal antibodies are not expected to alter DNA or chromosomes.

There were no adverse effects on surrogate markers of fertility (e.g., estrous cyclicity, testicular volume, ejaculate volume, sperm motility, or total sperm count per ejaculate) in a 6-month chronic toxicology study in sexually-mature monkeys subcutaneously administered at 5, 15, and 75 mg/kg/week at systemic exposures up to 103-fold the 150 mg every two weeks subcutaneous clinical dose based on serum AUC. In addition, there were no adverse alirocumab-related anatomic pathology or histopathology findings in reproductive tissues in rat or monkey toxicology studies at systemic exposures up to 11-fold and 103-fold respectively, in the 6-month studies, compared to clinical systemic exposure following a 150 mg every two weeks dose, based on serum AUC.

• The recommended dosage of PRALUENT for patients with a body weight less than 50 kg is 150 mg once every 4 weeks administered subcutaneously [see Dosage and Administration (2.4)].
  • If the LDL-C lowering response is inadequate, the dosage may be adjusted to 75 mg subcutaneously once every 2 weeks [see Dosage and Administration (2.4)].
• 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 [see Dosage and Administration (2.4)].
  • If the LDL-C lowering response is inadequate, the dosage may be adjusted to 150 mg subcutaneously once every 2 weeks [see Dosage and Administration (2.4)].
• Assess LDL-C when clinically appropriate. The LDL-lowering effect of PRALUENT may be measured as early as 4 weeks after initiation.

Trial 1 (ODYSSEY OUTCOMES, NTC01663402) was a multicenter, double-blind, placebo-controlled trial in 18,924 adult patients (9,462 PRALUENT; 9,462 placebo) followed for up to 5 years. Patients had an acute coronary syndrome (ACS) event 4 to 52 weeks prior to randomization and were treated with a lipid-modifying therapy (LMT) regimen that was statin-intensive (defined as atorvastatin 40 or 80 mg, or rosuvastatin 20 or 40 mg) or at maximally tolerated dose of a statin, with or without other LMT. Patients were randomized to receive either PRALUENT 75 mg or placebo once every two weeks.

At month 2, if additional LDL-C lowering was required based on pre-specified LDL-C criteria (LDL-C ≥50 mg/dL), PRALUENT was adjusted to 150 mg every 2 weeks. For patients who had their dose adjusted to 150 mg every 2 weeks and who had two consecutive LDL-C values below 25 mg/dL, down-titration from 150 mg every 2 weeks to 75 mg every 2 weeks was performed. Patients on 75 mg every 2 weeks who had two consecutive LDL-C values below 15 mg/dL were switched to placebo in a blinded fashion. Approximately 2,615 (27.7%) of 9,451 patients treated with PRALUENT required dose adjustment to 150 mg every 2 weeks. Of these 2,615 patients, 805 (30.8%) were down-titrated to 75 mg every 2 weeks. Overall, 730 (7.7%) of 9,451 patients switched to placebo.

A total of 99.5% of patients were followed for survival until the end of the trial. The median follow-up duration was 33 months.