Drug Trials Snapshots: LEQVIO
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic 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 healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the LEQVIO Prescribing Information for all of the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
LEQVIO (inclisiran)
(leck’ vee oh)
Novartis Pharmaceuticals Corp
Approval date: December 22, 2021
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
LEQVIO is a drug for the treatment of high low-density lipoprotein (LDL) cholesterol, which is sometimes referred to as “bad cholesterol”.
LEQVIO 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, such as heart attacks and strokes (known as atherosclerotic cardiovascular disease [ASCVD]).
How is this drug used?
LEQVIO is an injection that is given under the skin in the abdomen, upper arm, or thigh. It is given initially, again at 3 months, and then every 6 months. LEQVIO is used in addition to a 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.
Who participated in the clinical trials?
The FDA approved LEQVIO based on evidence from three placebo-controlled clinical trials (Trial 1/NCT03397121, Trial 2/NCT03399370, and Trial 3/NCT03400800) of 3,660 patients at cardiovascular risk with high LDL cholesterol. The benefits and side effects of LEQVIO was evaluated in 3,457 patients with high LDL cholesterol and known atherosclerotic cardiovascular disease or HeFH. The number of patients representing efficacy findings may differ from the number of patients representing safety findings due to different pools of study participants analyzed for efficacy and safety.
The trials were conducted in 13 countries: Canada, Czech Republic, Denmark, Germany, Hungary, Netherlands, Poland, South Africa, Spain, Sweden, Ukraine, United Kingdom, and the United States.
What are the benefits of this drug?
LEQVIO lowers LDL cholesterol.
What are the benefits of this drug (results of trials used to assess efficacy)?
Table 1 below summarizes the results for the primary efficacy endpoint, which was the mean percent LDL-C change after 17 months for LEQVIO compared with placebo, for each trial.
Table 1. Percent Change in LDL-C After 17 Months of Treatment1
| Trial | Mean Percent Change in LDL-C (95% CI) | Treatment Difference | |
|---|---|---|---|
| LEQVIO | Placebo | ||
| Trial 1 (HeFH) | -39.7 (-43.7, -35.6) | 8.2 (4.3, 12.2) | -47.9 (-53.5, -42.3) |
| Trials 2+3 (ASCVD) | -48.6 (-50.4, -46.8) | 2.5 (0.8, 4.2) | -51.0 (-53.4, -48.6) |
Source: Adapted from FDA Review
1 Treatments administered to patients while on background statin therapy
Abbreviations: ASCVD, atherosclerotic cardiovascular disease; HeFH, heterozygous familial hypercholesterolemia; LDL-C, low-density lipoprotein cholesterol
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
- Sex: LEQVIO worked similarly in males and females.
- Race: LEQVIO worked similarly in White and Black or African American patients. The number of patients of other races was small; therefore, differences in response among all races could not be determined.
- Age: LEQVIO worked similarly in patients younger and older than 65 years of age.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 2 and Table 3 below summarize the primary efficacy endpoint, the mean percent LDL-C change after 17 months of treatment, by demographic subgroups and trial.
Table 2. Subgroup Analysis: Percent Change in LDL-C After 17 Months of Treatment-Trial 1 (HeFH)
| Demographic Parameter | Treatment Difference in Mean Percent Change LDL-C (95% CI) |
||
|---|---|---|---|
| LEQVIO N=242 n (%) |
Placebo N=240 n (%) |
||
| Sex | |||
| Male | 112 (46.3) | 115 (47.9) | -48.3 (-54.7, -41.9) |
| Female | 130 (53.7) | 125 (52.1) | -47.5 (-53.8, -41.2) |
| Race | |||
| White | 226 (93.4) | 227 (94.6) | -47.7 (-53.4, -42.1) |
| Black or African American | 8 (3.3) | 7 (2.9) | -49.8 (-63.7, -36.0) |
| Other | 8 (3.3) | 6 (2.5) | -48.6 (-60.8, -36.4) |
| Age group (years) | |||
| 18 to 64 | 195 (80.6) | 190 (79.2) | -48.1 (-53.8, -42.4) |
| 65 or older | 47 (19.4) | 50 (20.8) | -47.4 (-55.0, -39.8) |
Source: Adapted from FDA Review
Treatment Differences and Credible Intervals based on a non-informative inverse gamma prior for the variance
Abbreviations: CI, credible interval; HeFH, heterozygous familial hypercholesterolemia; LDL-C, low-density lipoprotein cholesterol
Table 3. Subgroup Analysis: Percent Change in LDL-C After 17 Months of Treatment-Trials 2 and 3 (ASCVD)
| Demographic Parameter | Mean Percent Change in LDL-C | Treatment Difference in Percent Change LDL-C (95% CI) |
|
|---|---|---|---|
| LEQVIO N=1591 n (%) |
Placebo N=1587 n (%) |
||
| Sex | |||
| Male | 1114 (70.0) | 1129 (71.1) | -50.9 (-53.5, -48.2) |
| Female | 477 (30.0) | 458 (28.9) | -51.5 (-55.4, -47.6) |
| Race | |||
| White | 1444 (90.8) | 1481 (93.3) | -51.4 (-53.8, -48.9) |
| Black or African American | 122 (7.7) | 95 (6.0) | -47.3 (-55.0, -39.7) |
| Other | 25 (1.6) | 11 (0.7) | -48.5 (-59.8, -37.1) |
| Age group (years) | |||
| 18 to 64 | 736 (46.3) | 778 (49.0) | -51.9 (-55.1, -48.6) |
| 65 or older | 855 (53.7) | 809 (51.0) | -50.2 (-53.3, -47.1) |
Source: Adapted from FDA Review
Treatment Differences and Credible Intervals based on a half Cauchy prior for the variance
Abbreviations: ASCVD, atherosclerotic cardiovascular disease; CI, credible interval; LDL-C, low-density lipoprotein cholesterol
What are the possible side effects?
The most common side effects are pain, redness, or rash where the injection is given, aching or stiffness in joints, urinary tract infection, and diarrhea.
What are the possible side effects (results of trials used to assess safety)?
Table 4 below summarizes adverse reactions for the three 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 (>3% and Greater Than Placebo) in LEQVIO Treated Patients With ASCVD and HeFH (Trials 1, 2, and 3)
| Adverse Reactions | Placebo N=1822 % |
LEQVIO N=1833 % |
|---|---|---|
| Injection site reaction† | 1.8 | 8.2 |
| Arthralgia | 4.0 | 5.0 |
| Urinary tract infection | 3.6 | 4.4 |
| Diarrhea | 3.5 | 3.9 |
| Bronchitis | 2.7 | 4.3 |
| Pain in extremity | 2.6 | 3.3 |
| Dyspnea | 2.6 | 3.2 |
Source: LEQVIO Prescribing Information
† Includes related terms such as: injection site pain, erythema, and rash
Abbreviations: ASCVD, atherosclerotic cardiovascular disease; HeFH, heterozygous familial hypercholesterolemia
Were there any differences in side effects among sex, race and age?
- Sex: The occurrence of side effects was similar in males and females.
- Race: The occurrence of side effects was similar in White and Black or African American patients. The number of patients of other races was small; therefore, differences in the occurrence of side effects among all races could not be determined.
- Age: The occurrence of side effects was similar in patients younger and older than 65 years of age.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Table 5 below summarizes treatment emergent adverse events (TEAEs) in the safety population by subgroups.
Table 5. Subgroup Analyses of Subjects With at Least One TEAE (Safety Population)
| Demographic Subgroup | Placebo N=1822 n/N (%) |
LEQVIO N=1833 n/N (%) |
|---|---|---|
| Sex | ||
| Male | 952/1240 (76.8) | 949/1228 (77.3) |
| Female | 457/582 (78.5) | 481/605 (79.5) |
| Age, years | ||
| <65 | 656/ 882 (74.4) | 651/852 (76.4) |
| ≥65 | 753/940 (80.1) | 779/981 (79.4) |
| <75 | 1193/1570 (76.0) | 1235/1594 (77.5) |
| ≥75 | 216/252 (85.7) | 195/239 (81.6) |
| Race | ||
| White | 1332/1704 (78.2) | 1312/1669 (78.6) |
| Black or African American | 65/101 (64.4) | 93/131 (71.0) |
| Other | 12/17 (70.6) | 25/33 (75.8) |
Source: Adapted from FDA Review
Abbreviations: TEAE, treatment-emergent adverse events
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many male and female patients were enrolled in the combined clinical trials used to evaluate the efficacy and side effects of LEQVIO.
Figure 1. Baseline Demographics by Sex (Safety Population)
Source: Adapted from FDA Review
Figure 2 summarizes the percentage of patients by race enrolled in the combined clinical trials used to evaluate the efficacy and side effects of LEQVIO.
Figure 2. Baseline Demographics by Race (Safety Population)
Source: Adapted from FDA Review
* Includes American Indian or Alaska Native (n=8), Native Hawaiian or other Pacific Islander (n=12)
Figure 3 below summarizes how many patients by ethnicity were in the combined trials.
Figure 3. Baseline Demographics by Ethnicity (Safety Population)
Source: Adapted from FDA Review
Figure 4 below summarizes the percentage of patients by age in the clinical trials. In these trials, 492 (13%) patients were 75 years or older.
Figure 4. Baseline Demographics by Age (Safety Population)
Source: Adapted from FDA Review
Who participated in the trials?
Table 6 below summarizes baseline demographics for the trials (efficacy population).
Table 6. Demographics of Pooled Trials 1, 2, and 3 (Efficacy Population)
| Demographic Characteristics | Placebo N=1827 |
LEQVIO N=1833 |
Total N=3660 |
|---|---|---|---|
| Sex, n (%) | |||
| Male | 1244 (68.1) | 1226 (66.9) | 2470 (67.5) |
| Female | 583 (31.9) | 607 (33.1) | 1190 (32.5) |
| Age, years | |||
| Mean (SD) | 63.9 (9.9) | 64.1 (9.9) | 64.0 (9.9) |
| Median | 65.0 | 65.0 | 65.0 |
| Min, max | 21, 89 | 20, 90 | 20, 90 |
| Age group, years, n (%) | |||
| 18 to <65 | 884 (48.4) | 853 (46.5) | 1737 (47.5) |
| ≥65 | 943 (51.6) | 980 (53.5) | 1923 (52.5) |
| 18 to <75 | 1575 (86.2) | 1593 (86.9) | 3168 (86.6) |
| ≥75 | 252 (13.8) | 240 (13.1) | 492 (13.4) |
| Race, n (%) | |||
| White | 1708 (93.5) | 1670 (91.1) | 3378 (92.3) |
| Black or African American | 102 (5.6) | 130 (7.1) | 232 (6.3) |
| Asian | 8 (0.4) | 22 (1.2) | 30 (0.8) |
| American Indian or Alaska Native | 4 (0.2) | 4 (0.2) | 8 (0.2) |
| Native Hawaiian or other Pacific Islander | 5 (0.3) | 7 (0.4) | 12 (0.3) |
| Ethnicity, n (%) | |||
| Hispanic or Latino | 116 (6.3) | 120 (6.5) | 236 (6.4) |
| Not Hispanic or Latino | 1711 (93.7) | 1713 (93.5) | 3424 (93.6) |
| Region, n (%) | |||
| Canada | 11 (0.6) | 12 (0.7) | 23 (0.6) |
| Czech Republic | 16 (0.9) | 17 (0.9) | 33 (0.9) |
| Germany | 41 (2.2) | 42 (2.3) | 83 (2.3) |
| Denmark | 26 (1.4) | 23 (1.3) | 49 (1.3) |
| Spain | 42 (2.3) | 42 (2.3) | 84 (2.3) |
| United Kingdom | 231 (12.6) | 231 (12.6) | 462 (12.6) |
| Hungary | 52 (2.8) | 52 (2.8) | 104 (2.8) |
| Netherlands | 19 (1.0) | 19 (1.0) | 38 (1.0) |
| Poland | 357 (19.5) | 360 (19.6) | 717 (19.6) |
| Sweden | 16 (0.9) | 18 (1.0) | 34 (0.9) |
| Ukraine | 54 (3.0) | 55 (3.0) | 109 (3.0) |
| United States | 812 (44.4) | 814 (44.4) | 1626 (44.4) |
| South Africa | 150 (8.2) | 148 (8.1) | 298 (8.1) |
Source: Adapted from FDA Review
How were the trials designed?
The benefits and side effects of LEQVIO was evaluated in three double-blind, placebo-controlled clinical trials of 3,457 patients with high LDL cholesterol and known atherosclerotic cardiovascular disease or HeFH. 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) with or without other lipid modifying therapies. In all trials, patients were randomly assigned to receive either LEQVIO or placebo injections for 18 months. Neither the patients nor the health care providers knew which treatment was being given.
The trials measured percent change in LDL cholesterol blood levels from baseline to Day 510 and compared LEQVIO to placebo.
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.