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  6. Drug Trials Snapshots: NEXLETOL
  1. Resources for Information | Approved Drugs

Drug Trials Snapshots: NEXLETOL

 

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 NEXLETOL Prescribing Information for complete information.

NEXLETOL (bempedoic acid)
nex' leh tol
Esperion
Approval date: February 21, 2020


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

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

NEXLETOL 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 with complications from too much cholesterol (known as atherosclerotic cardiovascular disease-ASCVD), such as heart attacks and strokes.

How is this drug used?

NEXLETOL is a tablet used once daily, in addition to low cholesterol diet and the highest dose of a statin (another drug commonly used to lower cholesterol) that a patient can tolerate. It should only be taken when LDL cholesterol needs to be lowered further.

What are the benefits of this drug?

NEXLETOL lowers LDL cholesterol.

What are the benefits of this drug?

The table below summarizes the results for the primary efficacy endpoint, which was the mean percent LDL-C change at week 12 for NEXLETOL compared with placebo, for combined trials.

Table 2. Percent Change in LDL-C After 12 Weeks of Treatment1

Percent Change LDL-C (95% CI)

 

NEXLETOL

Placebo

Treatment Difference

-16.1 (-17.1, -15.2)

1.8 (0.4, 3.1)

-17.8 (-19.5, -16.2)

1 Treatments administered to patients while on background statin therapy
FDA Statistical Review-Analyses for Drug Trials Snapshot

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

  • Sex: NEXLETOL worked similarly in men and women.
  • Race: NEXLETOL worked similarly in White and Black or African-American patients. The number of patients of other races was limited; therefore, differences in response for other races could not be determined.
  • Age: NEXLETOL worked similarly in all age groups tested.

 

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

The table below summarizes the primary efficacy endpoint, the mean percent LDL-C change after 12 weeks of treatment, by demographic subgroups.

Table 3. Subgroup Analysis: Percent Change in LDL-C After 12 Weeks of Treatment-Trials 1 and 2

Demographic Parameter

LDL-C change (%)

Differencea
(95% CI)

NEXLETOL (95% CI)

Placebo
(95% CI)

                                Sex

Men

-15.4 (-16.4, -14.3)

1.6 (0.1, 3.1)

-17.0 (-18.9, -15.1)

Women

-17.9 (-19.9, -15.9)

2.2 (-0.5, 4.9)

-19.9 (-23.2, -16.6)

                                   Race

White

-16.2 (-17.1, -15.2)

1.7 (0.3, 3.0)

-17.8 (-19.5, -16.1)

Black or African American

-13.8 (-19, -8.6)

0.1 (-7.8, 8.1)

-15.0 (-23.0, -6.3)

                                    Age Group (years)

18 to 64

-16.6 (-18.1, -15.0)

1.2 (-1.1, 3.5)

-17.8 (-20.3, -15.2)

65 to 74

-16.2 (-17.6, -14.7)

2.0 (0.1, 4.0)

-18.1 (-20.5, -15.8)

75 or Older

-14.8 (-17.0, -12.5)

2.5 (-0.5, 5.5)

-17.4 (-20.7, -14.0)

a Treatment differences and credible intervals may not match values of (treatment - control) since estimates include relevance of outcomes from other subgroups.

FDA Statistical Review-Analyses for Drug Trials Snapshot

What are the possible side effects?

NEXLETOL may cause serious side effects including tendon rupture, and high uric acid levels in the blood.

The most common side effects of NEXLETOL are upper respiratory tract infection, increase in blood levels of uric acid, muscle cramps, back and extremity pain, stomach pain, bronchitis, anemia and elevated liver enzymes.

What are the possible side effects?

The table below summarizes adverse reactions for the two pooled trials. The population represented is the safety population, which includes any patient who received at least one dose of trial drug.

Table 4. Adverse Reactions (> 2% and Greater than Placebo) in NEXLETOL Treated Patients with ASCVD and HeFH (Trials 1 and 2)

Adverse Reaction

NEXLETOL + Statin and ± Other Lipid Lowering Therapies
(N = 2009)
%

Placebo
(N = 999)
%

Upper respiratory tract infection

4.5

4

Muscle spasms

3.6

2.3

Hyperuricemiaa

3.5

1.1

Back pain

3.3

2.2

Abdominal pain or discomfortb

3.1

2.2

Bronchitis

3.0

2.5

Pain in extremity

3.0

1.7

Anemia 

2.8

1.9

Elevated liver enzymesc

2.1

0.8

a. Hyperuricemia includes hyperuricemia and blood uric acid increased.
b. Abdominal pain or discomfort includes abdominal pain, abdominal pain upper, abdominal pain lower, and abdominal discomfort
c. Elevated liver enzymes include AST increased, ALT increased, hepatic enzyme increased, and liver function test increased

NEXLETOL Prescribing Information

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

  • Sex: The occurrence 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 occurrence of side effects was similar in patients younger and older than 65 of age.

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

The table below summarizes treatment emergent adverse events (TEAEs) in the safety population by subgroups.

Table 5. Subgroup Analyses of TEAEs (Safety Population)

Demographic Subgroup

NEXLETOL
N=2009

Placebo
N=999

 

x (%)

Total, n

x (%)

Total, n

Any TEAEs

1533 (76)

2009

766 (77)

999

Sex

 

 

 

 

  Men

1083 (76)

1427

521 (75)

697

  Women

450 (77)

582

245 (81)

302

Race

 

 

 

 

   White

1473 (77)

1913

744 (76)

960

  All Other

60 (63)

96

22 (56)

39

Age Group

 

 

 

 

  < 65 years

619 (71)

871

279 (73)

385

  ≥ 65 years

914 (80)

1138

487 (79)

614

Ethnicity

 

 

 

 

  Hispanic or Latino

27 (40)

67

12 (40)

30

  Not Hispanic or Latino

1506 (78)

1942

754 (78)

969

Clinical Trial Data

WHO WAS IN THE CLINICAL TRIALS?

Who participated in the clinical trials?

The FDA approved NEXLETOL based on evidence from two clinical trials (Trial 1/ NCT02666664 and Trial 2/NCT02991118) of 3009 patients with high LDL cholesterol and known atherosclerotic cardiovascular disease or HeFH. The trials were conducted in United States, Canada, and Europe.

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 in the clinical trial. In total, 885 women (29%) and 2124 men (71%) participated in the clinical trial.

Clinical Trial Data

The figure summarizes 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 clinical trial. In total, 2874 White (95%), 26 Asian (1%) and 93 Black or African American  (3%) and 16 Other (1%)

*Includes American Indian or Alaska Native, Multiple, Native Hawaiian or Pacific Islander, and Other

Clinical Trial Data

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

Figure 3. Baseline Demographics by Age

Pie charts summarizing how many individuals of certain age groups were enrolled in the clinical trial. In total,  1256 (42%) were less than 65 years, 1275 (42%) of patients were 65 to 74 year and 478 (16%) were 75 years and older.

Clinical Trial Data

Figure 4. Baseline Demographics by Ethnicity

Pie charts summarizing how many individuals of certain ethnicity were enrolled in the clinical trial. In total,  97 patients were Hispanic or Latino (3%), and 2912 patients were not Hispanic or Latino (97%)

Clinical Trial Data

Who participated in the trials?

The table below summarizes baseline demographics for the trials (efficacy population).

Table 6. Demographics of Pooled Trials 1 and 2 (Efficacy Population)

Demographic Characteristic

NEXLETOL
N=2010

Placebo
N=999

TOTAL
N=3009

Sex, n (%)

   

 

Men

1427 (71)

697 (70)

2124 (71)

Women

583 (29)

302 (30)

885 (29)

Race, n (%)

   

 

American Indian or Alaska Native

2 (<1)

2(<1)

4(<1)

Asian

18 (1)

8 (1)

26 (1)

Black or African American

66 (3)

27 (3)

93 (3)

Multiple

3 (<1)

0

3 (<1)

Native Hawaiian or Pacific Islander

3 (<1)

0

3 (<1)

Other

4 (<1)

2 (<1)

6 (<1)

White

1914 (95)

960 (96)

2874 (96)

Age, years

 

 

 

Mean (SD)

65.4 (9.06)

66.2 (8.70)

65.7 (8.95)

Median (min, max)

66 (24,91)

67 (28,88)

66 (24,91)

Age Group, n (%)

 

 

 

<65 years

871 (43)

385 (39)

1256 (42)

65-74 years

826 (41)

449 (45)

1275 (42)

≥75 years

313 (16)

165 (16)

478 (16)

Ethnicity, n (%)

   

 

Hispanic or Latino

67 (3)

30 (3)

97 (3)

Not Hispanic or Latino

1943 (97)

969 (97)

2912 (97)

Region, n (%)

 

 

 

United States

517 (26)

256 (26)

773 (26)

Canada

145 (7)

75 (7)

220 (7)

Europe

1348 (67)

668 (67)

2016 (67)

Clinical Trial Data

How were the trials designed?

There were two clinical trials that evaluated the benefits and side effects of NEXLETOL. The trial designs were similar.

All enrolled patients were on a low cholesterol diet and taking the highest dose of a statin (drug commonly used to lower cholesterol), for high cholesterol. In both trials, patients were randomly assigned to receive NEXLETOL or placebo tablets every day for 52-weeks. Neither the patients nor the health care providers knew which treatment was being given.

The trials measured percent change in LDL-C blood levels from baseline to week 12 and compared NEXLETOL to placebo.

How were the trials designed?

The efficacy and safety of NEXLETOL were investigated in two similarly designed multi-center, randomized, double-blind, placebo-controlled trials that enrolled adult patients with HeFH and/or ASCVD. All patients were receiving a maximally tolerated dose of a statin, with or without other lipid lowering therapies and maintained low cholesterol diet. Patients were randomized 2:1 to NEXLETOL or placebo tablets daily.

The trials evaluated the percent change in LDL-C from baseline to week 12 as the primary endpoint.

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.

LINK TO DRUG PRESCRIBING INFORMATION

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