Drug Trials Snapshots: SKYRIZI
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 SKYRIZI Package Insert for complete information.
SKYRIZI (risankizumab-rzaa)
Sky-RIZZ-ee
AbbVie, Inc.
Approval date: April 23, 2019
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
SKYRIZI is a drug for treatment of moderate to severe plaque psoriasis in adults who may benefit from taking injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet or UV light).
How is this drug used?
SKYRIZI is given as two injections under the skin (subcutaneous) 4 weeks apart for the initial two doses, then once every twelve weeks.
What are the benefits of this drug?
SKYRIZZI was better than placebo in improving signs and symptoms of plaque psoriasis. The benefit was maintained through follow up at one year.
What are the benefits of this drug (results of trials used to assess efficacy)?
The table below summarizes efficacy results for the evaluated patients in Trials 1 and 2. The co-primary endpoints were the proportion of patients who achieved a static Physician’s Global Assessment (sPGA) score of 0 (“clear”) or 1 (“almost clear”) and at least a 90% reduction from baseline Psoriasis Area and Severity Index (PASI 90).
Table 2. Efficacy Results at Week 16 in Adults with Plaque Psoriasis in Trial 1 and Trial 2
| Trial 1 | Trial 2 | |||
|---|---|---|---|---|
| SKYRIZI (N=304) n (%) |
Placebo (N=102) n (%) |
SKYRIZI (N=294) n (%) |
Placebo (N=98) n (%) |
|
| sPGA 0 or 1 (“clear or almost clear”)a | 267 (88) | 8 (8) | 246 (84) | 5 (5) |
| PASI 90a | 229 (75) | 5 (5) | 220 (75) | 2 (2) |
| sPGA 0 (“clear”) | 112 (37) | 2 (2) | 150 (51) | 3 (3) |
| PASI 100 | 109 (36) | 0 (0) | 149 (51) | 2 (2) |
a Co-primary endpoints
SKYRIZI Prescribing Information
Efficacy results for the evaluated patients in Trial 3 are presented below. The co-primary endpoints were the proportion of patients who achieved a static Physician’s Global Assessment (sPGA) score of 0 (“clear”) or 1 (“almost clear”) and at least a 90% reduction from baseline Psoriasis Area and Severity Index (PASI 90).
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
- Sex: SKYRIZI worked similarly in men and women.
- Race: Most of the patients were White. Differences in how well SKYRIZI worked among races could not be determined because of the limited number of patients in other races.
- Age: SKYRIZI 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?
The tables below summarize efficacy results by sex, race and age group.
Table 3. sPGA score of 0 or 1 at Week 16 by Sex, Race and Age Group for Trials 1 and 2
| Trial 1 | Trial 2 | |||||
|---|---|---|---|---|---|---|
| SKYRIZI | Placebo | Biologic Active control | SKYRIZI | Placebo | Biologic Active control | |
| Randomized | 294 | 98 | 99 | 304 | 102 | 100 |
| Sex | ||||||
| Men | 171/203 (84%) | 4/67 (6%) |
38/66 (58%) |
186/212 (88%) |
6/79 (8%) |
43/70 (61%) |
| Women | 75/91 (82%) |
1/31 (3%) |
23/33 (70%) |
81/92 (88%) |
2/23 (9%) |
20/30 (67%) |
| Race | ||||||
| White | 215/255 (84%) | 4/87 (5%) |
58/91 (64%) |
174/200 (87%) |
5/71 (7%) |
44/74 (59%) |
| Black or African American | 8/10 (80%) |
1/2 (50%) |
2/2 (100%) |
7/10 (70%) |
0/1 (0%) |
1/1 (100%) |
| Asian | 19/25 (76%) |
0/7 (0%) |
0/4 (0%) |
79/86 (92%) |
2/28 (7%) |
17/22 (77%) |
| American Indian or Alaska Native | 2/2 (100%) |
0/1 (0%) |
0 | 6/7 (86%) |
1/2 (50%) |
0/2 (0%) |
| Native Hawaiian or Other Pacific Islander |
0 | 0/1 (0%) |
1/1 (100%) |
1/1 (100%) |
0 | 1/1 (100%) |
| Other | 2/2 (100%) |
0 | 0/1 (0%) |
0 | 0 | 0 |
| Age Group | ||||||
| <65 years | 221/266 (83%) |
4/86 (5%) |
53/82 (65%) |
237/268 (88%) | 6/86 (7%) |
53/88 (60%) |
| ≥65 years | 25/28 (89%) |
1/12 (8%) |
8/17 (47%) |
30/36 (83%) |
2/16 (13%) |
10/12 (83%) |
FDA Review
What are the possible side effects?
SKYRIZI may lower the ability of the immune system to fight infections and may increase the risk of infections.
The most common side effects are upper respiratory infections, headache, tiredness, injection site reactions, and fungal infections.
Before starting SKYRIZI, patients should be evaluated for tuberculosis infection.
What are the possible side effects (results of trials used to assess safety)?
The table below summarizes adverse reactions in patients with moderate to severe plaque psoriasis in the combined five trials (safety population).
Table 4. Adverse Drug Reactions Occurring in ≥ 1% of Subjects on SKYRIZI through Week 16
| Adverse Drug Reactions |
SKYRIZI N = 1306 n (%) |
Placebo N = 300 n (%) |
|---|---|---|
| Upper respiratory infectionsa | 170 (13.0) | 29 (9.7) |
| Headacheb | 46 (3.5) | 6 (2.0) |
| Fatiguec | 33 (2.5) | 3 (1.0) |
| Injection site reactionsd | 19 (1.5) | 3 (1.0) |
| Tinea infectionse | 14 (1.1) | 1 (0.3) |
a Includes: respiratory tract infection (viral, bacterial or unspecified), sinusitis (including acute), rhinitis, nasopharyngitis, pharyngitis (including viral), tonsillitis
b Includes: headache, tension headache, sinus headache, cervicogenic headache
c Includes: fatigue, asthenia
d Includes: injection site bruising, erythema, extravasation, hematoma, hemorrhage, infection, inflammation, irritation, pain, pruritus, reaction, swelling, warmth
e Includes: tinea pedis, tinea cruris, body tinea, tinea versicolor, tinea manuum, tinea infection
SKYRIZI 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 were White. The occurrence of side effects was similar in White and Asian patients. Differences in the occurrence of side effects among races could not be determined because of the limited number of patients in other races.
- Age: The occurrence of side effects was similar in patients younger and older that 65 years of age.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
The table below summarizes the occurrence of treatment-emergent adverse events (TEAEs) by subgroup.
Table 5. Subgroup Analysis of TEAEs (safety population)
| Demographic Characteristics | SKYRIZI n/N (%) |
Placebo n/N (%) |
|---|---|---|
| Sex, n (%) | ||
| Men | 430/908 (47.4) | 104/219 (47.5) |
| Women | 208/398 (52.3) | 41/81 (50.6) |
| Race, n (%) | ||
| White | 505/1020 (49.5) | 113/240(47.1) |
| Black or African American | 16/49 (32.7) | 2/5 (40.0) |
| Asian | 110/216 (50.9) | 28/50 (56.0) |
| Age Group, n (%) | ||
| < 65 years | 582/1165 (50.0) | 128/261 (49.0) |
| > 65 years | 56/141 (39.7) | 17/39 (43.6) |
FDA Review
WHO WAS IN THE CLINICAL TRIALS?
Who participated in the clinical trials?
The FDA approved SKYRIZI based on evidence primarily from five clinical trials (Trial 1/NCT0202684370, Trial 2/NCT02684357, Trial 3/NCT02672852, Trial 4/ NCT02694523 and Trial 5/NCT02054481) of 1606 patients with moderate to severe plaque psoriasis. The trials were conducted in Asia, Canada, Europe, Mexico, South America, and the United States.
Figure 1 summarizes how many men and women were in the clinical trials used to evaluate safety.
Figure 1. Baseline Demographics by Sex
FDA Review
Figure 2 summarizes the percentage of patients by race in the clinical trials used to evaluate safety.
Figure 2. Baseline Demographics by Race
*Other includes American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander, and multiple
FDA Review
Table 1. Demographics of Trials by Race
| Race | Number of Patients | Percentage of Patients |
|---|---|---|
| White | 1260 | 78% |
| Black or African American | 54 | 3% |
| Asian | 266 | 17% |
| American Indian or Alaska Native | 14 | 1% |
| Native Hawaiian or other Pacific Islander | 6 | less than 1% |
| Other | 6 | less than 1% |
FDA Review
Figure 3 summarizes the percentage of patients by age in the clinical trials used to evaluate safety.
Figure 3. Baseline Demographics by Age
FDA Review
Who participated in the trials?
The table below summarizes the demographics of the patients in the clinical trials. The combined safety population from Trials 1, 2, 3, 4 and 5 is presented below.
Table 6. Demographics of Patients in the Clinical Trials (Safety Population)
| Demographic Characteristics | SKYRIZI N=1306 |
Placebo N=300 |
Total N=1606 |
|---|---|---|---|
| Sex | |||
| Men | 908 (70%) | 219 (73 %) | 1127 (70 %) |
| Women | 398 (30 %) | 81 (27 %) | 479 (30%) |
| Race | |||
| White | 1020 (78 %) | 240 (80 %) | 1260 (78 %) |
| Black or African American | 49 (4%) | 5 (2 %) | 54 (3 %) |
| Asian | 216 (17%) | 50 (17%) | 266 (17%) |
| American Indian or Alaska Native | 11 (1%) | 3 (1 %) | 14 (1%) |
| Native Hawaiian or Other Pacific Islander | 4 (<1%) | 2 (<1%) | 6 (<1%) |
| Other | 6 (<1%) | 0 (0) | 6 (<1%) |
| Age Group (years) | |||
| < 65 | 1165 (89 %) | 261 (87 %) | 1426 (89%) |
| 65 - 74 | 124 (10%) | 35 (12%) | 159 (10 %) |
| > 75 | 17 (1 %) | 4 (1 %) | 21(1%) |
| Ethnicity | |||
| Hispanic | 142 (11%) | 42 (14%) | 184 (11%) |
| Non-Hispanic | 1164 (89%) | 258 (86%) | 1422 (89%) |
| Region | |||
| Asia | 144 (11%) | 32 (11%) | 176 (11%) |
| Canada | 244 (19%) | 76 (25%) | 320 (20%) |
| Europe | 334 (25%) | 55 (18%) | 389 (24%) |
| Other | 36 (3%) | 8 (3%) | 44 (3%) |
| South America | 21 (2%) | 5 (2%) | 26 (2%) |
| United States | 524 (40%) | 124 (41%) | 648 (40%) |
Clinical Trial Data
How were the trials designed?
The benefit and side effects of SKYRIZI were evaluated in five clinical trials of patients with moderate to severe psoriasis. Neither the patients nor the health care providers knew which treatment was being given until after the first 16 weeks of the trials were completed.
Patients in Trials 1 and 2 received treatment with either SKYRIZI, placebo, or a drug approved to treat psoriasis at week 0, week 4, and every 12 weeks thereafter for a total of 40 weeks of treatment. Patients were followed for 52 weeks total to assess the duration of benefit.
Patients in Trial 3 received treatment with one of two doses of SKYRIZI or placebo. Patients received treatment at week 0, week 4, and every 12 weeks thereafter for a total of 44 weeks of treatment.
The efficacy of SKYRZI was evaluated in Trials 1, 2, and 3 after 16 weeks of treatment by scoring of the extent, nature and severity of psoriatic changes of the skin.
Patients in Trial 4 received treatment with SKYRIZI or a drug used to treat plaque psoriasis. Patients in the SKYRIZI group received treatment at week 0, week 4, and every 12 weeks thereafter. Patients in the other group received treatment at weeks 0, 1 and every other week through week 15. Starting at week 16, some patients were switched to SKYRIZI. Patients received treatment for 44 weeks.
Patients in Trial 5 received varying doses of SKYRIZI or another psoriasis treatment at weeks 0, 4, and 16.
Data from Trials 4 and 5 were primarily used to assess the side effects.
How were the trials designed?
The safety and efficacy of SKYRIZI were established in 5 randomized, double-blind, placebo and active-comparator controlled trials (Trials 1, 2, 3, and 4). All patients had moderate to severe plaque psoriasis for at least 6 months with a minimum body surface area involvement of 10%, a static Physician Global Assessment (sPGA) score of ≥3, a Psoriasis Area and Severity Index (PASI) score ≥12, and were candidates for phototherapy or systemic therapy.
In Trials 1 and 2, patients were randomized to SKYRIZI 150 mg, placebo, or a biologic active control at 0, 4, and every 12 weeks thereafter for a total of 40 weeks of treatment. The co-primary endpoints assessed at week 16 were the proportion of patients who achieved an sPGA score of 0 (clear) or 1 (almost clear), and the proportion of patients who achieved at least a 90% reduction from baseline PASI (PASI90)
In Trial 3, patients were randomized to SKYRIZI 150 mg, SKYRIZI 100 mg, or placebo. Patients received treatment at weeks 0, 4, and every 12 weeks thereafter for a total of 44 weeks of treatment. The co-primary endpoints assessed at week 16 were sPGA 0 and PASI 100.
In Trial 4, patients were randomized to SKYRIZI 150 mg at weeks 0, 4, and every 12 weeks thereafter or a biologic active control at week 0, 40 mg at week 1 and every other week through week 15. Starting at week 16, some patients were switched to SKYRIZI. Patients received treatment for a total of 44 weeks. The FDA used data from this trial to primarily assess side effects.
Trial 5 was a dose-ranging trial. Patients were randomized to one of 3 doses of SKYRIZI (18 mg at week 0, 90 mg at weeks 0, 4, 6 and 180 mg at weeks 0, 4 and 16) or a biologic active control at weeks 0, 4, and 16. The FDA used data from this trial to assess side effects.
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.