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  5. Drug Trials Snapshot: PRALUENT
  1. Development & Approval Process (Drugs)

Drug Trials Snapshot: PRALUENT

Drug Trials Snapshot: PRALUENT

HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race, and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.

LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to the PRALUENT Prescribing Information for complete information.

PRALUENT (alirocumab)
(PRAHL-u-ent)
Sanofi
Approval date: July 24, 2015


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

PRALUENT is a drug for the treatment of high LDL cholesterol, which is sometimes referred to as “bad cholesterol”.

PRALUENT is to be used in the following two groups of patients: 1) patients with an inherited condition called heterozygous familial hypercholesterolemia (HeFH) or 2) patients who have had complications of having too much cholesterol, such as heart attacks and strokes. It is approved to be used in addition to diet and the highest dose of a statin (another drug commonly used to lower cholesterol) that a patient can tolerate, and only when LDL cholesterol needs to be lowered further.

How is this drug used?

PRALUENT is an injection that is given under the skin in the thigh, abdomen, or upper arm once every two weeks.

What are the benefits of this drug?

PRALUENT lowers LDL cholesterol.

What are the benefits of this drug?

The efficacy of PRALUENT was investigated in five double-blind, placebo-controlled trials that enrolled 3499 patients.  Table 2 below summarizes the results for the primary efficacy endpoint, which was the mean percent change in LDL-C from baseline to week 24 for PRALUENT compared with placebo, for each trial.

Table 2. Percent Change in LDL C at Week 24 by Trial 
  Baseline
(mg/dL)
LS Mean:
% Change
Difference:
PRALUENT minus
placebo (95% CI)
Trial 1
PRALUENT 150mg (N=1553) 123 -58%  
Placebo (N=788) 122 1% -58% (-61, -56)
Trial 2
PRALUENT 75mg/150* mg (N=209) 100 -44%  
Placebo (N=107) 105 -2% -43% (-50, -35)
Trial 3 (HeFH only)
PRALUENT 75mg/150mg*  (N=323) 145 -47%  
Placebo (N=163) 144 9% -56% (-62, -51)
Trial 4 (HeFH only)
PRALUENT 75mg/150mg* (N=167) 135 -47%  
Placebo (N=82) 134 3% -50% (-57, -43)
Trial 5 (HeFH only)
PRALUENT 150mg (N=72) 196 -43%  
Placebo (N=35) 201 -7% -36% (-49, -24)

*Dosing reflects possible up-titration from 75 mg to 150 mg at week 12. 
Source: FDA Statistical Review 

Were there any differences in how well the drug worked in clinical trials among sex, race and age?

Subgroup analyses were conducted for sex, race, and age.

  • Sex: PRALUENT worked similarly in men and women.
  • Race:  The majority of patients in the trials were white. Differences in response to PRALUENT among races could not be determined.
  • Age: PRALUENT worked similarly in all age groups studied.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

The figure below summarizes the primary efficacy endpoint, the mean percent change in LDL-C from baseline to week 24, by sex, age, race, and ethnicity.  Data are provided combining the five placebo-controlled trials to allow for the largest possible sample sizes in each subgroup and since comparisons of the treatment effect across subgroups were consistent across trials.  Statistical tests assessing whether the treatment effect varied across subgroups are provided.

Figure 4: Difference (95% Confidence Interval) in Average Percent LDL-C Change at Week 24 (Praluent minus placebo); Trials 1 to 5 Combined (N=3499)

Table summarizes the primary efficacy endpoint, the mean percent change in LDL-C from baseline to week 24, by sex, age, race, and ethnicity.  Data are provided combining the five placebo-controlled trials to allow for the largest possible sample sizes in each subgroup and since comparisons of the treatment effect across subgroups were consistent across trials.  Statistical tests assessing whether the treatment effect varied across subgroups are provided.

P-value for statistical test measuring whether the treatment effect differs across subgroups (i.e., p-value for test of treatment-by-subgroup interaction) for studies 1 to 5 combined: Sex: 0.001; Age: 0.14; Race: 0.25; Ethnicity: 0.02 
Source: FDA Statistical Review and Evaluation for Drug Snapshot (PDF - 276 KB)

What are the possible side effects?

The most common side effects are common cold, injection site reactions, and flu.

PRALUENT may cause serious allergic reactions that require being hospitalized.

What are the possible side effects?

The table below summarizes adverse reactions from the nine placebo-controlled trials that were pooled for an evaluation of safety. The population represented is the Safety population, which includes any patient who received at least one dose of trial drug (Praluent or placebo).

Table 3. Adverse Reactions Occurring in Greater Than or Equal to 2% of PRALUENT-Treated Patients and More Frequently than with Placebo

Adverse Reactions Placebo
(N=1276)
PRALUENTa
(N=2476)
Nasopharyngitis 11.1% 11.3%
Injection site reactionsb 5.1% 7.2%
Influenza 4.6% 5.7%
Urinary tract infection 4.6% 4.8%
Diarrhea 4.4% 4.7%
Bronchitis 3.8% 4.3%
Myalgia 3.4% 4.2%
Muscle spasms 2.4% 3.1%
Sinusitis 2.7% 3.0%
Cough 2.3% 2.5%
Contusion 1.3% 2.1%
Musculoskeletal pain 1.6% 2.1%

a 75 mg every 2 weeks and 150 mg every 2 weeks combined
b includes erythema/redness, itching, swelling, pain/tenderness
Source: PRALUENT Prescribing Information, Section 6, Table 1  

Were there any differences in side effects among sex, race and age?

Subgroup analyses were conducted for sex, race, and age.

  • Sex: The risk of side effects was similar in men and women.
  • Race: The majority of patients in the trials were white. Differences in side effects among races could not be determined.
  • Age: The risk of side effects was similar in all age groups studied.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

The table below summarizes injection site reactions in nine placebo-controlled trials by subgroups. The population represented is the Safety population, which includes any patient who received at least one dose of trial drug (Praluent or placebo).

Table 4. Subgroup Analysis of Adverse Event-Injection Site Reaction

Subgroup PRALUENT
(N=2476)
Placebo
(N=1276)
Hazard Ratio 95% CI
n (%) Total, N n (%) Total, N LL UL
Any Injection Site Reaction 179 (7.2) 2476 65 (5.1) 1276 1.48 1.12 1.97
Sex
  Male 91 (6.1) 1482 29 (3.8) 763 1.68 1.1 2.55
  Female 88 (8.9) 994 36 (7.0) 513 1.27 0.86 1.88
Age Group 
below 65 years 142 (8.5) 1671 43 (4.9) 878 1.85 1.32 2.62
65 years and above 37 (4.6) 805 22 (5.5) 398 0.84 0.49 1.42
Race
  White 167 (7.5) 2232 59 (5.2) 1136 1.5 1.12 2.03
  Black or African American 5 (5.0) 101 3 (5.3) 57 0.73 0.16 3.38
  Asian 4 (5.3) 75 1 (2.7) 37 2 0.22 17.9
  American Indian or Alaska Native 0 32 1 (5.3) 19 NE NE NE
  Native Hawaiian or Other Pacific Islander 0 0 0 2 NE NE NE
  Other 3 (8.3) 36 1 (4.0) 25 1.88 0.19 18.94

N=not evaluated
Source: Company Clinical Trial Data  

WHO WAS IN THE CLINICAL TRIALS?

Who participated in the clinical trials?

The FDA approved PRALUENT based on evidence including that from nine clinical trials of 3752 patients.

The figure below summarizes how many men and women were in these clinical trials.

Figure 1. Baseline Demographics by Sex

Pie chart summarizing how many men and women were enrolled in the clinical trials PRALUENT

Source:  Company Clinical Data

The figure and table below summarize the percentage of patients by race in these clinical trials.

Figure 2. Baseline Demographics by Race

Pie chart summarizing the percentage of patients by race enrolled in the PRALUENT clinical trial

Source: Company Clinical Data

Table 1. Baseline Demographics by Race

Race  Number of Patients  Percentage of Patients
White 3368 90%
Black or African American 158 4%
Asian 112 3%
American Indian or Alaska Native 51 1%
Native Hawaiian or Other Pacific Islander 2 <>
Other 61 2%

Source: Company Clinical Data

The figure below summarizes the percentage of patients by age in the clinical trials.

Figure 3. Baseline Demographics by Age

Pie chart summarizing how many individuals of certain age groups were enrolled in the PRALUENT clinical trial

Source: Company Clinical Data

Who participated in the trials?

The table below summarizes baseline demographics for a pool of nine placebo-controlled trials (safety population).

Table 5. Baseline Demographics

Demographic Parameters PRALUENT
(N=2476)
n (%)*
Placebo
(N=1276)
n (%)
Total(N=3752)
n (%)
Sex
  Male 1482 (60) 763 (60) 2245 (60)
  Female 994 (40) 513 (40) 1507 (40)
Age
  Mean years (SD) 58.6 (11.6) 58.5 (11.3) 58.6 (11.4)
  Median (years) 60 59 60
  Min, Max (years) 18, 89 19, 87 18, 89
Age Group
below 65 years 1671 (68) 878 (69) 2549 (68)
65 years and above 805 (32) 398 (31) 1203 (32)
Race  
  White 2232 (90) 1136 (89) 3368 (90)
  Black or African American 101 (4) 57 (4) 158 (4)
  Asian 75 (3) 37 (3) 112 (3)
  American Indian or Alaska Native 32 (1) 19 (1) 51 (1)
  Native Hawaiian or Other Pacific Islander 0 2 (<> 2 (<>
  Other 36 (2) 25 (2) 61 (2)
Ethnicity 
  Hispanic or Latino 153 (6) 77 (6) 230 (6)
  Not Hispanic or Latino 2268 (94) 1172 (94) 3440 (94)
Region  
United States 725 (29) 384 (30) 1109 (30)
Rest of the world 1751 (71) 892 (70)  2643 (70)

Source: Company Clinical Trial Data 

How were the trials designed?

Nine double-blind, placebo-controlled trials composed a pool for safety assessment. All patients were receiving a maximally tolerated dose of a statin, with or without other lipid modifying therapies. Patients received either PRALUENT or placebo injections subcutaneously every two weeks. Five of these trials also supported the assessment of efficacy, with the primary endpoints being the percent change in LDL-C from baseline to week 24.

How were the trials designed?

Nine double-blind, placebo-controlled trials composed a pool for safety assessment. All patients were receiving a maximally tolerated dose of a statin, with or without other lipid modifying therapies. Patients received either PRALUENT or placebo injections subcutaneously every two weeks. Five of these trials also supported the assessment of efficacy, with the primary endpoints being the percent change in LDL-C from baseline to week 24.

There were nine placebo-controlled trials that contributed to the evaluation of the side effects of PRALUENT. Five of these trials were also central to the evaluation of the benefit of PRALUENT. In each of these trials, patients were randomly assigned to receive PRALUENT or placebo injections. Neither the patients nor the health care providers knew which treatment was being given until after the trials were completed.

The benefit of PRALUENT (the percent change in LDL-C blood levels) was measured at 24 weeks.

GLOSSARY

CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.

PRESCRIBING INFORMATION

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