PRALUENT is indicated to reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease.

In adults with a prior MI or unstable angina,

PRALUENT significantly reduced the risk of MACE and is the ONLY PCSK9i with an observed reduction in all-cause mortality

Because statistical testing of the all-cause mortality endpoint was performed outside of the hierarchy, this result is not considered statistically significant.

~90% of patients in ODYSSEY OUTCOMES were on a high-intensity statin1

(primary composite endpoint)1:

15
%
RRR
HR: 0.85
(95% CI: 0.78, 0.93)
P=0.0003

Components of the primary endpoint 1*

  • 8% RRR of CHD death
  • 14% RRR of nonfatal MI
  • 27% RRR of stroke (fatal or nonfatal)
  • 39% RRR of UA requiring hospitalization

*RRR for the components of the primary endpoint were associated with reduction in the risk of CHD death (HR: 0.92; 95% CI: 0.76, 1.11), nonfatal MI (HR: 0.86; 95% Cl: 0.77, 0.96), fatal or nonfatal stroke (HR: 0.73; 95% Cl: 0.57, 0.93), and unstable angina requiring hospitalization (HR: 0.61; 95% Cl: 0.41, 0.92).1

CHD death was not statistically significant. Because statistical testing of the remaining component endpoints was performed outside of the hierarchy, the results are not considered statistically significant.1,2

(seconday endpoint)1:

15
%
RRR
HR: 0.85
(95% CI: 0.73, 0.98)

Mortality endpoint

  • Because statistical testing of this endpoint was performed outside of the hierarchy, this result is not considered statistically significant2

The 75 mg PRALUENT dose was used 78% of the time in the study2

The 75 mg PRALUENT dose was used 78% of the time in the study2

In adults with a prior MI or unstable angina,

PRALUENT significantly reduced all-cause mortality, nonfatal stroke, and nonfatal MI (secondary composite endpoint)2

ODYSSEY OUTCOMES is the longest PCSK9i CV outcomes trial to date based on median follow-up of 2.8 years1,2

In adults with a prior MI or unstable angina,

PRALUENT demonstrated consistent outcomes across endpoints

Evaluated in ~19,000 patients in the ODYSSEY OUTCOMES trial1

In ODYSSEY OUTCOMES.

§Unstable angina requiring hospitalization.

CHD event defined as: major CHD event, unstable angina requiring hospitalization, ischemia-driven coronary revascularization procedure.2

Major CHD event defined as: CHD death and nonfatal MI.1

#Cardiovascular event defined as follows: CV death, any nonfatal CHD event, and nonfatal ischemic stroke.1

**The hierarchical analysis was stopped after the first nonsignificant P value was observed, in accordance with the hierarchical testing plan. Subsequent endpoints are not statistically significant.1

In adults with established cardiovascular disease,

PRALUENT demonstrated powerful and sustained levels of LDL-C reduction

LDL-C reduction in ODYSSEY OUTCOMES2

ODYSSEY OUTCOMES (Study 1): A multicenter, double-blind, placebo-controlled trial comparing PRALUENT (n=9462) with placebo (n=9462) in adults who were hospitalized with an ACS event 4 to 52 weeks prior to randomization and were treated with a lipid-modifying-therapy (LMT) regimen that was statin-intensive or at maximally tolerated dose of a statin, with or without other LMT. Mean baseline LDL-C was 92.4 mg/dL. The primary composite endpoint was the time to first occurrence of MACE (CHD death, nonfatal MI, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization). Patients were randomized to receive PRALUENT 75 mg Q2W or placebo Q2W. Up-titration to PRALUENT 150 mg Q2W occurred at month 2 in 27.7% of patients based on prespecified LDL-C criteria (LDL-C ≥50 mg/dL); 30.8% of up-titrated patients were down-titrated to the 75 mg Q2W dose. Patients with 2 consecutive LDL-C values below 15 mg/dL (7.7%) were switched to placebo in a blinded fashion. The median follow-up was 2.8 years.1

  • In the intention-to-treat analysis, mean LDL-C levels were 92 mg/dL at baseline. At month 48, they were reduced to 66 mg/dL with PRALUENT vs 103 mg/dL with placebo2
  • The on-treatment analysis excluded values measured after discontinuation of PRALUENT and after blinded substitution of placebo for PRALUENT2

from baseline at 24 weeks with PRALUENT 75 mg Q2W/150 mg Q2W vs +7% from placebo (P<0.0001) in the FH I and FH II Studies1

FH I and FH II (Studies 4 and 5) were 2 multicenter, placebo-controlled, double-blind trials that compared PRALUENT (n=490) with placebo (n=245). 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. The mean age was 52 years (range 20-87), 45% were women, 94% were Caucasian, 1% were Black, and 3% were Hispanic/Latino. The average LDL-C at baseline was 141 mg/dL. The primary efficacy endpoint, measured at week 24, was the mean percent change in LDL-C from baseline. Patients started on PRALUENT 75 mg Q2W in addition to existing statin therapy: Up-titration to 150 mg Q2W occurred at week 12 in patients (42%) who did not achieve their predefined target LDL-C (<70 mg/dL or <100 mg/dL based on CV risk) at week 8.1

HeFH diagnosis by genotyping or by clinical criteria1

  • “Definite FH” using either the Simon Broome or WHO/DUTCH Lipid Clinic Network criteria

LDL-C reduction at 24 weeks on top of maximally tolerated statins (vs ezetimibe) in the COMBO II Study with PRALUENT 75 mg Q2W/150 mg Q2W1,4

COMBO II (Study 9) was a multicenter, double-blind, ezetimibe-controlled trial that compared PRALUENT (n=479) with ezetimibe (n=241). Patients were taking maximally tolerated doses of statins and required additional LDL-C reduction. Patients received either PRALUENT 75 mg Q2W or ezetimibe 10 mg once daily in addition to their existing statin therapy. Up-titration of PRALUENT to 150 mg Q2W occurred at week 12 in patients with LDL-C ≥70 mg/dL at week 8. 18% of PRALUENT patients needed to be up-titrated at week 12 from 75 mg to 150 mg Q2W.1,5

82% OF PATIENTS ACHIEVED LDL-C GOAL (<70 mg/dL) at week 8 and did not require dose adjustment at week 12 in the COMBO II Study1,5

  • In COMBO II, adverse reactions occurring in ≥5% of PRALUENT-treated patients and more frequently than with ezetimibe were accidental overdose, upper respiratory tract infection, hypertension, headache, and arthralgia4

LDL-C lowering power with the

from baseline at 24 weeks with PRALUENT 300 mg Q4W/150 mg Q2W vs -1% for placebo (P<0.0001) in the cohort of patients on background statin in the CHOICE I Study1,6

CHOICE I (Study 7) was a multicenter, double-blind, placebo-controlled trial that compared PRALUENT 300 mg Q4W (n=458), PRALUENT 75 mg Q2W (n=115), and placebo (n=230). Patients were stratified based on whether or not they were treated concomitantly with statin. The mean age was 61 years (range 21-88), 42% were women, 87% were Caucasian, 11% were Black, and 3% were Hispanic/Latino. In the cohort of patients on background statin, the mean baseline LDL-C was 113 mg/dL. A primary efficacy endpoint measure at week 24 was the mean percent change in LDL-C from baseline. The dose was up-titrated to 150 mg Q2W at week 12, based on prespecified LDL-C criteria at week 8, in approximately 20% of patients treated with PRALUENT 75 mg Q2W or 300 mg Q4W.1

The recommended starting dose of PRALUENT is 75 mg once every 2 weeks administered subcutaneously or alternatively 300 mg once every 4 weeks (monthly) for patients who prefer less frequent dosing. The majority of patients achieve sufficient LDL-C reduction with the 75 mg dosage. If the LDL-C response is inadequate after 4 to 8 weeks of initiating PRALUENT, the dosage may be adjusted to the maximum dosage of 150 mg administered every 2 weeks.1

  • PRALUENT once-monthly 300 mg dose: Administered as 2 consecutive, subcutaneous 150 mg injections at 2 different injection sites every 4 weeks1

  • For patients receiving PRALUENT 300 mg every 4 weeks, measure LDL-C just prior to the next scheduled dose, since in some patients LDL-C can vary considerably between doses with this regimen.2 If LDL-C reduction is inadequate, the dose may be adjusted to 150 mg every 2 weeks, starting the new dose on the next scheduled dosing date1
  • The once-monthly (Q4W) 300-mg dosing regimen had a higher rate of local injection site reactions as compared to PRALUENT 75 mg Q2W or placebo (16.6%, 9.6%, and 7.9%, respectively) in a trial in which all patients received an injection of drug or placebo every 2 weeks to maintain the blind. The discontinuation rate due to injection site reactions was 0.7% in the 300 mg Q4W arm and 0% in the other 2 arms1

from baseline at 24 weeks with PRALUENT 75 mg Q2W/150 mg vs -2% for placebo (P<0.0001) in the COMBO I Study1

COMBO I (Study 3) was a multicenter, double-blind, placebo-controlled trial that compared PRALUENT (n=209) with placebo (n=107). Patients were taking maximally tolerated doses of statins with or without other lipid-modifying therapy, and required additional LDL‑C reduction. The mean age was 63 years (range 39-87), 34% were women, 82% were Caucasian, 16% were Black, and 11% were Hispanic/Latino. Mean baseline LDL-C was 102 mg/dL.1

with PRALUENT 150 mg Q2W vs +1% for placebo at week 24 (P<0.0001) in the LONG TERM Study1

LONG TERM trial (Study 2) was a multicenter, double-blind, placebo-controlled trial that compared PRALUENT 150 mg Q2W (n=1553) with placebo (n=788). The average LDL-C at baseline was 122 mg/dL.1

LDL-C reductions with PRALUENT as monotherapy1

In patients with moderate CV risk, PRALUENT as monotherapy had significant and consistent LDL-C reduction1

  • The mean percent change in LDL-C at week 24 from baseline was -45% with PRALUENT vs -14% with ezetimibe
  • The treatment difference between PRALUENT and ezetimibe in mean LDL-C percent change was -31% (95% CI: -40%, -22%; P<0.0001)

MONO (Study 10) was a multicenter, double-blind, ezetimibe-controlled trial comparing PRALUENT 75 mg Q2W (n=52) to ezetimibe 10 mg/day (n=51) in patients with moderate CV risk, not taking statins or other lipid-modifying therapies. Baseline LDL-C was between 100 mg/dL and 190 mg/dL.1

PRALUENT was studied in the longest PCSK9i CV outcomes trial to date based on a median follow-up time of 2.8 years

Evaluated in ~19,000 patients with established CV disease1,2

requiring hospitaliztion 1-12 months prior to randomization (median 2.6 months)1,2

(atorvastatin 40-80 mg/day or rosuvastatin 20-40 mg/day)1,2

A total of 99.5% of patients were followed for survival until the end of the trial. The median follow-up duration was 2.8 years1,2

Primary Endpoint1

  • Length of time until patients experienced a MACE occurrence, defined as:
    • CHD death
    • Nonfatal MI
    • Fatal or nonfatal ischemic stroke
    • Unstable angina requiring hospitalization

Major Secondary Endpoints2

  • In order of hierarchical testing
    • CHD event (including CHD death, nonfatal MI, UA requiring hospitalization, and an ischemia-driven coronary revascularization procedure)
    • Major CHD event (including death from CHD and nonfatal MI)
    • CV event (including any nonfatal CHD event, death from CV causes, or nonfatal ischemic stroke)
    • Composite of all-cause death, nonfatal MI, nonfatal ischemic stroke
    • CHD death
    • CV death
    • All-cause death

Double-blind treatment period (~2 to 5 years)1

Dosing to target range

At month 2, if additional LDL-C lowering was required based on prespecified LDL-C criteria (LDL-C ≥50 mg/dL), PRALUENT was adjusted to 150 mg Q2W. For patients who had their dose adjusted to 150 mg Q2W and who had 2 consecutive LDL-C values below 25 mg/dL, down-titration from 150 mg Q2W to 75 mg Q2W was performed. Patients on 75 mg Q2W who had 2 consecutive LDL-C values below 15 mg/dL were switched to placebo in a blinded fashion. Approximately 2615 (27.7%) of 9451 patients treated with PRALUENT required dose adjustment to 150 mg Q2W. Of these 2615 patients, 805 (30.8%) were down-titrated to 75 mg Q2W. Overall, 730 (7.7%) of 9451 patients switched to placebo.1

In adults with established cardiovascular disease,

PRALUENT was generally well tolerated

  • In ODYSSEY OUTCOMES, the adverse events that occurred in >5% of patients treated with PRALUENT and occurring more frequently than placebo included: non-cardiac chest pain (7.0% PRALUENT, 6.8% placebo), nasopharyngitis (6.0% PRALUENT, 5.6% placebo), and myalgia (5.6% PRALUENT, 5.3% placebo)1
  • In ODYSSEY OUTCOMES, local injection site reactions were reported in 3.8% of patients treated with PRALUENT vs 2.1% of patients treated with placebo and led to permanent discontinuation in 26 patients (0.3%) vs 3 patients (<0.1%), respectively1
In 9 primary hyperlipidemia placebo-controlled trials, adverse reactions occuring in ≥2% of PRALUENT-treated patients and more frequently than with placebo1

Adverse Reactions1,2

PRALUENT
(n=2476)

Placebo
(n=1276)

Nasopharyngitis

11.3%

11.1%

Injection site reactions‡‡

7.2%

5.1%

Influenza

5.7%

4.6%

Urinary tract infection

4.8%

4.6%

Diarrhea

4.7%

4.4%

Bronchitis

4.3%

3.8%

Myalgia

4.2%

3.4%

Muscle spasms

3.1%

2.4%

Sinusitis

3.0%

2.7%

Cough

2.5%

2.3%

Contusion

2.1%

1.3%

Musculoskeletal pain

2.1%

1.6%

75 mg every 2 weeks and 150 mg every 2 weeks combined.

‡‡Includes erythema/redness, itching, swelling, pain/tenderness.

  • In 9 primary hyperlipidemia placebo-controlled trials, 2135 patients were exposed to PRALUENT for at least 6 months and 1999 patients were exposed to PRALUENT for more than 1 year (median treatment duration of 65 weeks)1

Discontinuation rates with PRALUENT (5.3% for both 75 mg and 150 mg doses) were similar to placebo (5.1%)1

  • The most common adverse reactions leading to treatment discontinuation in patients treated with PRALUENT were allergic reactions (0.6% vs 0.2% for PRALUENT and placebo, respectively) and elevated liver enzymes (0.3% vs <0.1%)

Hypersensitivity reactions

  • Hypersensitivity reactions (eg, pruritus, rash, urticaria), including some serious events (eg, hypersensitivity vasculitis, angioedema, and hypersensitivity reactions requiring hospitalization), have been reported with PRALUENT treatment. If signs or symptoms of serious allergic reactions occur, discontinue treatment with PRALUENT, treat according to the standard of care, and monitor until signs and symptoms resolve

Local injection site reactions

  • Erythema/redness, itching, swelling, and pain/tenderness were more frequent in patients treated with PRALUENT 75 mg/150 mg Q2W (7.2% vs 5.1% for PRALUENT and placebo, respectively)
    • Few patients discontinued treatment because of these reactions (0.2% vs 0.4% for PRALUENT and placebo, respectively), but patients receiving PRALUENT had a greater number of injection site reactions, had more reports of associated symptoms, and had reactions of longer average duration than patients receiving placebo
  • Local injection site reactions were reported more frequently in patients treated with PRALUENT 300 mg Q4W compared to those receiving PRALUENT 75 mg Q2W or placebo (16.6%, 9.6%, and 7.9%, respectively) in a trial in which all patients received an injection of drug or placebo every 2 weeks to maintain the blind
    • Three patients (0.7%) treated with PRALUENT 300 mg Q4W discontinued treatment due to local injection site reactions vs no patients (0%) in the other 2 treatment groups

Liver enzyme abnormalities

  • Abnormalities in liver enzymes were reported in 2.5% of patients treated with PRALUENT and 1.8% of patients treated with placebo, leading to treatment discontinuation in 0.4% and 0.2% of patients, respectively
  • Increases in serum transaminases to greater than 3 times the upper limit of normal occurred in 1.7% of patients treated with PRALUENT and 1.4% of patients treated with placebo

Immunogenicity

  • As with all therapeutic proteins, there is a potential for immunogenicity with PRALUENT

Low LDL-C values

  • In the placebo- and active-controlled clinical trials using an every-2-weeks or every-4-weeks dosing interval, 914 PRALUENT-treated patients had 2 consecutive calculated LDL-C values <25 mg/dL, and 335 had 2 consecutive calculated LDL-C values <15 mg/dL. LDL-C <25 mg/dL and <15 mg/dL were observed more frequently in patients treated with the PRALUENT 150 mg Q2W or 300 mg Q4W dosing regimens
  • Changes to background lipid-altering therapy (eg, maximally tolerated statins) were not made in response to low LDL-C values, and PRALUENT dosing was not modified or interrupted on this basis
  • Although adverse consequences of very low LDL-C were not identified in these trials, the long-term effects of very low levels of LDL-C induced by PRALUENT are unknown
  • In ODYSSEY OUTCOMES, 4305 PRALUENT-treated patients had 2 consecutive calculated LDL-C values <25 mg/dL, and 782 had 2 consecutive calculated LDL-C values <15 mg/dL. Because PRALUENT dosing was decreased or discontinued in the event of 2 consecutive LDL-C values <15 mg/dL in this trial, the effects of prolonged very low LDL-C with PRALUENT are unknown

ACS = acute coronary syndrome; CHD = coronary heart disease; CI = confidence interval; CV = cardiovascular; HR = hazard ratio; LMT = lipid-modifying therapy; MI = myocardial infarction; RRR = relative risk reduction; UA = unstable angina.

Find appropriate patients for PRALUENT

INDICATIONS AND USAGE

PRALUENT is 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 lipid-lowering therapies (e.g., statins, ezetimibe), for the treatment of adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) to reduce low-density lipoprotein cholesterol (LDL-C).
Important Safety Information
  • PRALUENT is contraindicated in patients with a history of a serious hypersensitivity reaction to PRALUENT, including hypersensitivity vasculitis and hypersensitivity reactions requiring hospitalization.
  • Hypersensitivity reactions (e.g., pruritus, rash, urticaria), including some serious events (e.g., hypersensitivity vasculitis, angioedema, and hypersensitivity reactions requiring hospitalization), have been reported with PRALUENT treatment. If signs or symptoms of serious allergic reactions occur, discontinue treatment with PRALUENT, treat according to the standard of care, and monitor until signs and symptoms resolve.
  • The most commonly occurring adverse reactions in clinical trials in primary hyperlipidemia (including heterozygous familial hypercholesterolemia (HeFH)) (≥5% of patients treated with PRALUENT and occurring more frequently than with placebo) are nasopharyngitis, injection site reactions, and influenza.
  • The most commonly occurring adverse reactions in the cardiovascular outcomes trial (>5% of patients treated with PRALUENT and occurring more frequently than placebo) were non-cardiac chest pain, nasopharyngitis, and myalgia.
  • In the primary hyperlipidemia (including HeFH) clinical trials, local injection site reactions including erythema/redness, itching, swelling, and pain/tenderness were reported more frequently in patients treated with PRALUENT 75 mg and/or 150 mg every 2 weeks (7.2% versus 5.1% for PRALUENT and placebo, respectively). Few patients discontinued treatment because of these reactions (0.2% versus 0.4% for PRALUENT and placebo, respectively), but patients receiving PRALUENT had a greater number of injection site reactions, had more reports of associated symptoms, and had reactions of longer average duration than patients receiving placebo.
  • The once-monthly (Q4W) 300mg dosing regimen had a higher rate of local injection site reactions as compared to PRALUENT 75mg Q2W or placebo (16.6%, 9.6%, and 7.9%, respectively) in a trial in which all patients received an injection of drug or placebo every 2 weeks to maintain the blind. The discontinuation rate due to injection site reactions was 0.7% in the 300 mg Q4W arm and 0% in the other 2 arms.
  • In a cardiovascular outcomes trial, local injection site reactions were reported in 3.8% of patients treated with PRALUENT versus 2.1% patients treated with placebo, and led to permanent discontinuation in 0.3% of patients versus <0.1% of patients, respectively.
  • In the primary hyperlipidemia trials, liver-related disorders (primarily related to abnormalities in liver enzymes) were reported in 2.5% of patients treated with PRALUENT and 1.8% of patients treated with placebo, leading to treatment discontinuation in 0.4% and 0.2% of patients, respectively. Increases in serum transaminases to greater than 3 times the upper limit of normal occurred in 1.7% of patients treated with PRALUENT and 1.4% of patients treated with placebo.
  • In the primary hyperlipidemia trials, 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%).
  • PRALUENT is a human monoclonal antibody. As with all therapeutic proteins, there is a potential for immunogenicity with PRALUENT.
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Important Safety Information
  • PRALUENT is contraindicated in patients with a history of a serious hypersensitivity reaction to PRALUENT, including hypersensitivity vasculitis and hypersensitivity reactions requiring hospitalization.
  • Hypersensitivity reactions (e.g., pruritus, rash, urticaria), including some serious events (e.g., hypersensitivity vasculitis, angioedema, and hypersensitivity reactions requiring hospitalization), have been reported with PRALUENT treatment. If signs or symptoms of serious allergic reactions occur, discontinue treatment with PRALUENT, treat according to the standard of care, and monitor until signs and symptoms resolve.
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