Drug Trials Snapshots: KEVZARA
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 KEVZARA Prescribing Information for complete information.
KEVZARA (sarilumab)
(KEV-za-ra)
Sanofi-Aventis
Approval date: May 22, 2017
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
KEVZARA is used to treat adult patients with moderately to severely active rheumatoid arthritis (RA) after at least one other medicine called a disease modifying anti-rheumatic drug (DMARD) has been used and did not work well or could not be tolerated.
How is this drug used?
KEVZARA is given as an injection under the skin (subcutaneous injection) once every two weeks.
What are the benefits of this drug?
In the clinical trials, a greater proportion of patients who received KEVZARA achieved an improvement in the signs and symptoms of RA in comparison to patients who received a placebo.
What are the benefits of this drug (results of trials used to assess efficacy)?
The table below summarizes the efficacy results for individual trials. In both trials, the primary endpoint was the proportion of patients who achieved an ACR20 response at Week 24.
Table 2. Clinical Response in Placebo-Controlled Trials 1 and 2 in Adults with Moderately to Severely Active RA*
| Percentage of Patients | ||||||
|---|---|---|---|---|---|---|
| Trial 1 | Trial 2 | |||||
| Placebo + MTX N=398 | KEVZARA 150 mg + MTX N=400 | KEVZARA 200 mg + MTX N=399 | Placebo + DMARD(s) † N=181 | KEVZARA 150 mg + DMARD(s) † N=181 | KEVZARA 200 mg + DMARD(s) † N=184 | |
| Week 24§ | 33.4% | 58.0% | 66.4% | 33.7% | 55.8% | 60.9% |
| Difference from placebo, (95% CI)‡ | 24.6% (18.0%, 31.3%) | 33.0% (26.5%, 39.5%) | 22.1% (12.6%, 31.6%) | 27.4% (17.7%, 37.0%) | ||
* Patients who were rescued or discontinued were considered non-responders for the analyses included in this table.
In Trial 1, at week 52, 196, 270, and 270 patients remained on placebo, KEVZARA 150 mg, and KEVZARA 200 mg respectively.
† DMARDs in Trial 2 included MTX, sulfasalazine, leflunomide, and/or hydroxychloroquine
‡Weighted estimate of the rate difference; CI=confidence interval
§ Primary end point
Adapted from KEVZARA Prescribing Information
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
- Sex: KEVZARA worked similarly in men and women.
- Race: Most of the patients were White. Differences in how well the drug worked among races could not be determined because of the small number of patients in other races.
- Age: KEVZARA worked similarly in patients above and below age 65.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
The tables below summarize subgroup results based on the primary endpoint analyses for KEVZARA 200 mg and 150 mg, respectively.
Table 3. Subgroup Analyses on ACR20 Response at Week 24 for KEVZARA 200 mg Compared to Placebo
| Demographic Parameter | Placebo | KEVZARA 200 mg + DMARD | Odds ratio (95% CI) | ||
|---|---|---|---|---|---|
| N | n (%) | N | n (%) | ||
| Overall | 579 | 194 (34) | 583 | 377 (65) | 3.7 (2.9, 4.8) |
| Sex | |||||
| Men | 104 | 36 (35) | 95 | 57 (60) | 3.2 (1.7, 5.8) |
| Women | 475 | 158 (33) | 488 | 320 (66) | 4.0 (3.0, 5.2) |
| Age | |||||
| ≤50 years | 260 | 96 (37) | 256 | 178 (70) | 4.3 (2.9, 6.3) |
| >50 years | 319 | 98 (31) | 327 | 199 (61) | 3.4 (2.5, 4.8) |
| ≤65 years | 520 | 179 (34) | 514 | 342 (67) | 3.9 (3.0, 5.1) |
| >65 years | 59 | 15 (25) | 69 | 35 (51) | 2.9 (1.4,6.3) |
| Race | |||||
| White | 467 | 153 (33) | 473 | 309 (65) | 4.0 (2.0, 5.3) |
| All Other | 112 | 41 (37) | 110 | 68 (62) | 2.9 (1.6, 5.0) |
N = number of patients randomized
n (%) = number (percent) of patients achieving an ACR20 response
Table 4. Subgroup Analyses on ACR20 Response at Week 24 for KEVZARA 150 mg Compared to Placebo
| Demographic Parameter | Placebo | KEVZARA 150 mg + DMARD | Odds ratio (95%CI) | ||
|---|---|---|---|---|---|
| N | n (%) | N | n (%) | ||
| Overall | 579 | 194 (34) | 581 | 333 (57) | 2.8 (2.2, 3.5) |
| Sex | |||||
| Men | 104 | 36 (35) | 120 | 67 (56) | 2.5 (1.5, 4.4) |
| Women | 475 | 158 (33) | 461 | 266 (58) | 2.8 (2.2, 3.7) |
| Age | |||||
| ≤50 years | 260 | 96 (37) | 254 | 149 (59) | 2.7 (1.8, 3.8) |
| >50 years | 319 | 98 (31) | 327 | 184 (56) | 2.9 (2.1, 4.0) |
| ≤65 years | 520 | 179 (34) | 520 | 299 (58) | 2.7 (2.1,3.5) |
| >65 years | 59 | 15 (35) | 61 | 34 (56) | 3.9 (1.7,8.8) |
| Race | |||||
| White | 467 | 153 (33) | 479 | 274 (57) | 2.8 (2.1, 3.6) |
| All Other | 112 | 41 (37) | 102 | 59 (58) | 3.1 (1.7, 5.6) |
N = number of patients randomized
n (%) = number (percent) of patients achieving an ACR20 response
Adapted from FDA Statistical review
What are the possible side effects?
KEVZARA may cause life threatening infections. Other serious side effects include low neutrophil (white blood cells that help the body fight off infections) count, low platelet (blood cells that promote blood clotting) count, increased certain liver function tests, increased cholesterol, stomach or intestine tears and allergic reactions.
The most common side effects are low neutrophil count, increased certain liver function tests, injection site erythema, upper respiratory infections and urinary tract infections.
What are the possible side effects (results of trials used to assess safety)?
Below is the summary of the most common adverse reactions observed in patients treated with KEVZARA or placebo.
Table 5. Common Adverse Reactions* in Adults with Moderately to Severely Active Rheumatoid Arthritis †
| Preferred Term | Placebo + DMARD (N=579) | KEVZARA 150 mg + DMARD (N=579) | KEVZARA 200 mg + DMARD (N=582) |
|---|---|---|---|
| Neutropenia | 0.2% | 7% | 10% |
| Alanine aminotransferase increased | 2% | 5% | 5% |
| Injection site erythema | 0.9% | 5% | 4% |
| Injection site pruritus | 0.2% | 2% | 2% |
| Upper respiratory tract infection | 2% | 4% | 3% |
| Urinary tract infection | 2% | 3% | 3% |
| Hypertriglyceridemia | 0.5% | 3% | 1% |
| Leukopenia | 0% | 0.9% | 2% |
* Adverse reactions occurring in 2% or more in the 150mg KEVZARA + DMARD or 200mg KEVZARA +
DMARD groups and greater than observed in Placebo + DMARD
†Pre-rescue, placebo-controlled population (Weeks 0-16 for Trial 1, Weeks 0-12 for Trial 2)
KEVZARA 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: Most of the patients were White. Differences in the occurrence of side among races could not be determined because of the small number of patients in other races.
- Age: The occurrence of side effects was similar in participants above and below age 65.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Tables below summarize the occurrence of adverse events of interest by subgroups. This was based on the larger safety population that includes additional patients from Part A of Trial 1 (a phase 2 study) and follows patients through the end of study rather than pre-rescue (52 weeks for Trial 1 and 24 weeks for Trial 2).
Table 6. Subgroup Analysis by Sex
| Placebo + DMARD | KEVZARA 150 mg + DMARD | KEVZARA 200 mg + DMARD | |
|---|---|---|---|
| Women | 538 | 527 | 551 |
| Any adverse event | 313 (58%) | 376 (71%) | 414 (75%) |
| Serious adverse event | 25 (5%) | 34 (7%) | 52 (9%) |
| Any infection | 160 (30%) | 186 (35%) | 195 (35%) |
| Men | 123 | 133 | 110 |
| Any adverse event | 65 (53%) | 89 (67%) | 74 (67%) |
| Serious adverse event | 6 (5%) | 8 (6%) | 7 (6%) |
| Any infection | 29 (24%) | 41 (31%) | 38 (35%) |
Table 7. Subgroup Analysis by Race
| Placebo + DMARD | KEVZARA 150 mg + DMARD | KEVZARA 200 mg + DMARD | |
|---|---|---|---|
| White | 543 | 553 | 545 |
| Any adverse event | 311 (57%) | 388 (70%) | 400 (73%) |
| Serious adverse event | 26 (5%) | 37 (7%) | 52 (10%) |
| Any infection | 156 (28%) | 194 (35%) | 187 (34%) |
| Black or African American | 17 | 21 | 18 |
| Any adverse event | 7 (41%) | 14 (67%) | 14 (78%) |
| Serious adverse event | 1 (6%) | 0 | 1 (6%) |
| Any infection | 2 (12%) | 7 (33%) | 9 (50%) |
| Asian | 38 | 37 | 36 |
| Any adverse event | 25 (66%) | 27 (73%) | 31 (86%) |
| Serious adverse event | 2 (5%) | 8 (8%) | 4 (11%) |
| Any infection | 8 (21%) | 12 (32%) | 16 (44%) |
| All Other | 63 | 49 | 62 |
| Any adverse event | 35 (56%) | 36 (74%) | 43 (69%) |
| Serious adverse event | 2 (3%) | 2 (4%) | 2 (3%) |
| Any infection | 23 (37%) | 14 (29%) | 21 (34%) |
Table 8. Subgroup Analysis by Age
| Placebo + DMARD | KEVZARA 150 mg + DMARD | KEVZARA 200 mg + DMARD | |
|---|---|---|---|
| 65> | 573 | 574 | 569 |
| Any adverse event | 326 (57%) | 406 (71%) | 418 (74%) |
| Serious adverse event | 24 (4) | 35 (6) | 42 (7%) |
| Any infection | 166 (29%) | 200 (35%) | 194 (34%) |
| 65-75 years | 84 | 79 | 82 |
| Any adverse event | 49 (58%) | 54 (68%) | 63 (77%) |
| Serious adverse event | 7 (8%) | 7 (9%) | 16 (20%) |
| Any infection | 22 (26%) | 24 (30%) | 35 (43%) |
| ≥75 years | 4 | 7 | 10 |
| Any adverse event | 3 (75%) | 5 (71%) | 7 (70%) |
| Serious adverse event | 0 | 0 | 1 (10%) |
| Any infection | 1 (25) | 3 (43) | 4 (40%) |
Clinical trial data
WHO WAS IN THE CLINICAL TRIALS?
Who participated in the clinical trials?
The FDA approved KEVZARA based primarily on evidence from two clinical trials of 1740 patients with moderate to severe RA who had an inadequate response or intolerance to one or more DMARDs. The trials were conducted in the United States, Europe, Asia, Australia, and Latin and South America.
Figure 1 summarizes how many men and women were in the clinical trials.
Figure 1. Baseline Demographics by Sex
Clinical trial data
Figure 2 and Table 1 summarize the percentage of patients by race in the clinical trials.
Figure 2. Baseline Demographics by Race
Clinical trial data
Table 1. Baseline Demographics by Race
| Race | Number of Patients | Percentage |
|---|---|---|
| White | 1418 | 81 |
| Black or African American | 48 | 3 |
| Asian | 102 | 6 |
| Other | 172 | 10 |
Clinical trial data
Figure 3 summarizes the percentage of patients by age in the clinical trials.
Figure 3. Baseline Demographics by Age
Clinical trial data
Who participated in the trials?
The table below summarizes demographics of patients (safety population) in clinical Trials 1 and 2 combined.
Table 9. Baseline and Demographics (Safety Population)
| Demographic Parameter | Placebo + DMARD (N=579) | KEVZARA 150 mg + DMARD (N=579) | KEVZARA 200 mg + DMARD (N=582) | Total (N=1740) |
|---|---|---|---|---|
| Sex, n (%) | ||||
| Men | 104 (18) | 120 (21) | 95 (16) | 319 (18) |
| Women | 475 (82) | 459 (79) | 487 (84) | 1421 (82) |
| Age (years) | ||||
| Mean (SD) | 51.2 (11.6) | 51.4 (11.9) | 51.5 (12.2) | 51.3 (11.9) |
| Median | 52 | 53 | 53 | 52 |
| Min, Max | 19,79 | 18,88 | 19,87 | 18,88 |
| Age Group (years) n (%) | ||||
| > | 509 (88) | 507 (88) | 501 (86) | 1517 (87) |
| 65 to 75 | 66 (11) | 65 (11) | 71 (12) | 202 (12) |
| ≥75 | 4 (1) | 7 (1) | 10 (2) | 21 (1) |
| Race | ||||
| White | 467 (81) | 478 (83) | 473 (81) | 1418 (81) |
| Black or African American | 17 (3) | 18 (3) | 13 (2) | 48 (3) |
| Asian | 33 (6) | 35 (6) | 34 (6) | 102 (6) |
| All Other* | 62 (10) | 48 (8) | 62 (11) | 172 (10) |
| Ethnicity | ||||
| Hispanic | 216 (37) | 230 (40) | 239 (41) | 685 (39) |
| Not Hispanic | 363 (63) | 349 (60) | 343 (59) | 1055 (61) |
*includes Mixed and Multiracial
Clinical trial data
How were the trials designed?
There were two trials that established the benefits and side effects of KEVZARA. Trials enrolled patients with moderately to severely active RA who had an inadequate response or intolerance to one or more DMARDs (Trial 1) or one or more TNF-inhibitors (Trial 2).
In Trial 1, patients taking methotrexate were randomly assigned to receive either KEVZARA (150 mg or 200 mg) or placebo every two weeks for 52 weeks. Neither the patients nor the health care providers knew which injection was being given until after the trial was completed.
In Trial 2, patients taking conventional DMARDS (methotrexate, sulfasalazine, leflunomide, and/or hydroxychloroquine) were randomly assigned to receive either KEVZARA (150 mg or 200 mg) or placebo every two weeks for 24 weeks. Neither the patients nor the health care providers knew which injection was being given until after the trial was completed.
The benefit of KEVZARA was measured by comparing the proportion of patients treated with KEVZARA who achieved an American College of Rheumatology 20 (ACR20) response at Week 24 to the proportion of patients treated with placebo who achieved an ACR20 response. ACR20 response is based on standardized criteria used to assess the benefit of arthritis medications on signs and symptoms of RA, such as improvement in the number of tender and swollen joints.
How were the trials designed?
There were two randomized, multicenter, double-blind, placebo control trials that evaluated safety and efficacy of KEVZARA in patents with moderately to severely active rheumatoid arthritis.
In Trial 1, patients who had an inadequate clinical response to methotrexate (MTX) received subcutaneous KEVZARA 200 mg, KEVZARA 150 mg, or placebo every two weeks with concomitant MTX.
In Trial 2, patients who had an inadequate clinical response or were intolerant to one or more TNF-inhibitors received subcutaneous KEVZARA 200 mg, KEVZARA 150 mg, or placebo every two weeks with concomitant conventional DMARD(s) (MTX, sulfasalazine, leflunomide, and/or hydroxychloroquine).
In both trials, the primary efficacy endpoint was the proportion of patients who achieved an American College of Rheumatology 20 (ACR20) response at Week 24.
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