Regeneron is committed to helping patients with familial hypercholesterolemia (FH)

In addition to adults with HeFH, PRALUENT is now indicated as an adjunct to other LDL-C–lowering therapies to lower LDL-C in adults with homozygous familial hypercholesterolemia (HoFH).

PRA.21.04.0004

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 in the ODYSSEY OUTCOMES trial, 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 endpoint1*

  • 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

(secondary 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 significant1

Additional all-cause mortality analyses3

  • 22% RRR in all-cause mortality in patients with 3 to 5 years of follow-up (n=8242) (HR: 0.78; 95% CI: 0.65, 0.94)
  • 4% RRR in all-cause mortality in patients with <3 years of follow-up (n=10,682) (HR: 0.96; 95% CI: 0.76, 1.21)
  • The treatment effect of alirocumab on all-cause mortality was not observed during the first year (HR: 1.01; 95% CI: 0.77, 1.32) but was evident after the first year (HR: 0.79; 95% CI: 0.66, 0.94)

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

Risk of composite all-cause mortality,
nonfatal stroke, nonfatal MI

(HR: 0.86; 95% Cl: 0.79, 0.93; P<0.001)2,4

PRALUENT
+ high-intensity statin
± other LMTs (n=9462)
Placebo
+ high-intensity statin
± other LMTs (n=9462)

Adapted from Schwartz GG et al. N Engl J Med. 2018;379:2097-2107.3

All-cause mortality1

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

Nonfatal ischemic stroke4

27
%
RRR
HR: 0.73
(95% Cl: 0.56, 0.94)

Nonfatal MI1

14
%
RRR
HR: 0.86
(95% Cl: 0.77, 0.96)
Because statistical testing of these individual endpoints was performed outside of the hierarchy, these results are not considered statistically significant.
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 a prior MI or unstable angina,

PRALUENT delivered a higher absolute risk reduction in MACE in patients with diabetes††

Test Alt
  • In ODYSSEY OUTCOMES, the overall absolute risk reduction in MACE was 1.6% (95% CI: 0.7, 2.4)5
  • Consistent RRR of MACE, no matter the glycemic status5
    • Normoglycemia: 15% RRR (HR: 0.85; 95% Cl: 0.70, 1.03)
    • Prediabetes: 14% RRR (HR: 0.86; 95% Cl: 0.74, 1.00)
    • Diabetes: 16% RRR (HR: 0.84; 95% Cl: 0.74, 0.97)
  • PRALUENT did not increase the risk of new-onset diabetes for patients with prediabetes or normoglycemia at baseline5

Patients with diabetes have a substantially higher risk of MACE compared with patients without diabetes††

††Patients were classified by glycemic status at baseline (normoglycemia, prediabetes, or diabetes) defined on the basis of patient history, review of medical records, or baseline HbA1c or fasting serum glucose, and risk of new-onset diabetes among those without diabetes at baseline.5

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

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

requiring hospitalization
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

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, and 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, including hypersensitivity vasculitis, angioedema, and other 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
    • 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

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® (alirocumab) 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 low-density lipoprotein cholesterol (LDL-C) lowering therapies in adults with primary hyperlipidemia including heterozygous familial hypercholesterolemia (HeFH) to reduce LDL-C.
  • as an adjunct to other LDL-C-lowering therapies in adults with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C.
Important Safety Information
  • PRALUENT is contraindicated in patients with a history of a serious hypersensitivity reaction to alirocumab or any of the excipients in PRALUENT. Hypersensitivity reactions, including hypersensitivity vasculitis, angioedema, and other 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) 300 mg 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). 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 alirocumab or any of the excipients in PRALUENT. Hypersensitivity reactions, including hypersensitivity vasculitis, angioedema, and other 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.
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