Drug Trials Snapshots: ILUMYA
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 ILUMYA Package Insert for complete information.
ILUMYA (tildrakizumab-asmn)
e-loom’-me-a
Merck Sharp & Dohme Corp.
Approval date: March 20, 2018
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
ILUMYA is a drug for treatment of moderate to severe plaque psoriasis, in adults, who may benefit from taking injections or pills (systemic therapy) or treatment using ultraviolet or UV light (phototherapy).
How is this drug used?
ILUMYA is an injection given under the skin. The first two injections are given 4 weeks apart, followed by an injection once every 12 weeks.
What are the benefits of this drug?
ILUMYA was better than placebo in improving symptoms of plaque psoriasis and maintaining the improvement through at least a year of treatment.
What are the benefits of this drug (results of trials used to assess efficacy)?
Table 2 below summarizes the efficacy results for Trials 2 and 3. Demographics of this population (efficacy population) is presented in Table 8 under MORE INFO section.
Efficacy assessment at Week 12 of treatment was based on the two co-primary endpoints: 1) the proportion of subjects with a Physicians Global Assessment (PGA) score of 0 (clear) or 1 (minimal) and at least a 2-point improvement from baseline and 2) Psoriasis Area and Severity Index (PASI) 75, the proportion of subjects that achieved at least a 75% reduction in the PASI composite score that takes into consideration both, the percentage of body surface area affected as well as the nature and severity of psoriatic changes (induration, erythema, and scaling) within the affected region.
Results are presented using the efficacy, or ITT (Intent to Treat), population.
Table 2. Efficacy Results at Week 12 in Adults with Plaque Psoriasis in Trials 2 and 3 (NRI*)
| Trial 2 | Trial 3 | |||
|---|---|---|---|---|
| ILUMYA (N=309) n (%) | Placebo (N=154) n (%) | ILUMYA (N=307) n (%) | Placebo (N=156) n (%) | |
| PGA of 0 or 1†,‡ | 179 (58) | 11 (7) | 168 (55) | 7 (4) |
| PASI 75† | 197 (64) | 9 (6) | 188 (61) | 9 (6) |
*NRI = Non-Responder Imputation
† Co-Primary Endpoints
‡ PGA score of 0 (cleared) or 1 (minimal)
Adapted from ILUMYA Prescribing Information
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
- Sex: ILUMYA worked similarly in men and women.
- Race: The majority of patients were White. The number of patients in other races was limited; therefore, differences in response among races could not be determined.
- Age: The number of patients above 65 years of age was limited; therefore, differences in response between patients above and below 65 years of age could not be determined.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
The figures below summarize the efficacy results by subgroup for Trials 2 and 3 based on the efficacy, or ITT, population.
Figure 4. Results for the Co-Primary Efficacy Endpoints at Week 12 for Trial 2
n[I]= number of patients in ILUMYA subgroup; n[P] number of patients in placebo subgroup
Adapted from FDA Review
Figure 5. Results for the Co-Primary Efficacy Endpoints at Week 12 for Trial 3
n[I]= number of patients in ILUMYA subgroup; n[P] number of patients in placebo subgroup
Adapted from FDA Review
What are the possible side effects?
ILUMYA may cause serious side effects including excessive allergic reactions and infections. Before starting ILUMYA, patients should be evaluated for tuberculosis.
The most common side effects of ILUMYA are upper respiratory infections, injection site reactions, and diarrhea.
What are the possible side effects (results of trials used to assess safety)?
The table below summarizes adverese reactions in patients with moderate to severe plaque psoriasis, who received at least one dose of ILUMYA, in Trials 1, 2, and 3 (safety population).
Table 3. Adverse Reactions Occurring in ≥1% of Subjects in the ILUMYA Group and More Frequently than in the Placebo Group in the Plaque Psoriasis Trials 1, 2, and 3
| Adverse Reaction | ILUMYA (N=705) N (%) | Placebo (N=355) N (%) |
|---|---|---|
| Upper respiratory infectionsa | 98 (14) | 41 (12) |
| Injection-site reactionsb | 24 (3) | 7 (2) |
| Diarrhea | 13 (2) | 5 (1) |
a Upper respiratory infections include nasopharyngitis, upper respiratory tract infection, viral upper respiratory tract infection, and pharyngitis.
b Injection site reactions include injection site urticaria, pruritus, pain, reaction, erythema, inflammation, edema, swelling, bruising, hematoma, and hemorrhage.
ILUMYA Prescribing Information
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 were White. The number of patients in other races was limited; therefore, differences in side effects among races could not be determined.
- Age: The majority of patients were below 65 years of age. The difference in side effects between patients below and above age 65 years could not be determined.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
The tables below summarize adverse reactions (ARs) by subgroup for the pooled safety population from Trials 1, 2, and 3.
Table 4. Upper Respiratory Infections ARs by Demographic Subgroup
| Subgroups | ILUMYA (N=705) m/n* (%) | Placebo (N=355) m/n* (%) |
|---|---|---|
| Sex | ||
| Males | 70/503 (13.9) | 29/249 (11.6) |
| Females | 28/202 (13.9) | 12/106 (11.3) |
| Race | ||
| White | 77/569 (13.5) | 35/278 (12.6) |
| Black | 1/21 (4.8) | 1/7 (14.3) |
| Asian | 16/93 (17.2) | 5/56 (8.9) |
| Other | 1/22 (4.5) | 0/14 (0.0) |
| Age (years) | ||
| > | 94/644 (14.6) | 39/319 (12.2) |
| > 65 | 4/61 (6.6) | 2/36 (5.6) |
*m/n = number of participants with adverse reaction (m) in the subgroup (n)
FDA Review
Table 5. Injection-site Reactions by Demographic Subgroup
| Subgroups | ILUMYA (N=705) m/n* (%) | Placebo (N=355) m/n* (%) |
|---|---|---|
| Sex | ||
| Males | 15/503 (3.0) | 4/249 (1.6) |
| Females | 9/202 (4.5) | 3/106 (2.8) |
| Race | ||
| White | 23/569 (4.0) | 7/278 (2.5) |
| Black | 0/21 (0.0) | 0/7 (0.0) |
| Asian | 0/93 (0.0) | 0/56 (0.0) |
| Other | 1/22 (4.5) | 0/14 (0.0) |
| Age (years) | ||
| > | 23/644 (3.6) | 6/319 (1.9) |
| > 65 | 1/61 (1.6) | 1/36 (2.8) |
*m/n = number of participants with adverse reaction (m) in the subgroup (n)
FDA Review
Table 6. Diarrhea ARs by Demographic Subgroup
| Subgroups | ILUMYA (N=705) m/n* (%) | Placebo (N=355) m/n* (%) |
|---|---|---|
| Sex | ||
| Males | 9/503 (1.8) | 4/249 (1.6) |
| Females | 4/202 (2.0) | 2/106 (1.9) |
| Race | ||
| White | 13/569 (2.3) | 6/278 (2.2) |
| Black | 0/21 (0.0) | 0/7 (0.0) |
| Asian | 0/93 (0.0) | 0/56 (0.0) |
| Other | 0/22 (0.0) | 0/14 (0.0) |
| Age (years) | ||
| > | 10/644 (1.6) | 5/319 (1.6) |
| > 65 | 3/61 (4.9) | 1/36 (2.8) |
*m/n = number of participants with adverse reaction (m) in the subgroup (n)
FDA Review
WHO WAS IN THE CLINICAL TRIALS?
Who participated in the clinical trials?
The FDA approved ILUMYA based on evidence from three clinical trials of 1,060 patients with moderate to severe plaque psoriasis.
Trial 1 (NCT01225731) was conducted at 65 sites in the following 12 countries: Austria, Belgium, Canada, Denmark, France, Germany, Hungary, Finland, Japan, Norway, United Kingdom, and the United States.
Trial 2 (NCT01722331) was conducted at 112 sites in the following 5 countries: Australia, Canada, Japan, United Kingdom, and the United States.
Trial 3 (NCT01729754) was conducted at 123 sites in the following 9 countries: Austria, Belgium, Canada, Czech, Denmark, France, Germany, Hungary, and the United States.
Figures 1 – 3 below summarize by sex, race, and age how many patients participated in the three combined clinical trials (safety population).
Figure 1. Baseline Demographics by Sex (safety population)
FDA Review
Figure 2 summarizes the percentage of patients by race enrolled in the clinical trials used to evaluate efficacy.
Figure 2. Baseline Demographics by Race (safety population)
FDA Review
Table 1. Baseline Demographics by Race (safety population)
| Race | Number of Patients | Percentage of Patients |
|---|---|---|
| White | 847 | 80 |
| Black or African American | 28 | 3 |
| Asian | 149 | 14 |
| Other | 27 | 3 |
| Missing | 9 | less than 1 |
FDA Review
Figure 3. Baseline Demographics by Age (safety population)
FDA Review
Who participated in the trials?
Table 7. Baseline Demographics: Trials 1, 2, and 3 (Safety Population)
| ILUMYA (N=705) | Placebo (N=355) | Total (N=1060) | |
|---|---|---|---|
| Sex | |||
| Male | 503 (71%) | 249 (70%) | 752 (71%) |
| Female | 202 (29%) | 106 (30%) | 308 (29%) |
| Race | |||
| White | 569 (81%) | 278 (78%) | 847 (80%) |
| Black or African American | 21 (3%) | 7 (2%) | 28 (3%) |
| Asian | 93 (13%) | 56 (16%) | 149 (14%) |
| Other | 18 (3%) | 9 (3%) | 27 (3%) |
| Missing | 4 (1%) | 5 (1%) | 9 (> |
| Age | |||
| Mean (SD) | 45.5 (13.3) | 47.0 (12.8) | 46.0 (13.1) |
| Median | 45.0 | 47.0 | 46.0 |
| Range | 18 to 82 | 19 to 76 | 18 to 82 |
| Age Group | |||
| 65=""> | 644 (91%) | 319 (90%) | 963 (91%) |
| ≥ 65 years | 61 (9%) | 36 (10%) | 97 (9%) |
| Ethnicity | |||
| Hispanic | 60 (9%) | 35 (10%) | 95 (9%) |
| Non-Hispanic | 635 (90%) | 314 (88%) | 949 (90%) |
| Not Reported | 3 (> | 1 (> | 4 (> |
| Unknown | 4 (1%) | 2 (> | 6 (> |
| Missing | 3 (> | 3 (1%) | 6 (> |
| Country | |||
| U.S. | 231 (33%) | 119 (34%) | 350 (33%) |
| Non-U.S. | 474 (67%) | 236 (66%) | 710 (67%) |
FDA Review
Table 8. Baseline Demographics: Trials 2 and 3 (Efficacy Population)
| Trial 2 | Trial 3 | |||
|---|---|---|---|---|
| ILUMYA (N=309) | Placebo (N=155) | ILUMYA (N=307) | Placebo (N=156) | |
| Sex | ||||
| Male | 207 (67%) | 100 (65%) | 220 (72%) | 112 (72%) |
| Female | 102 (33%) | 55 (35%) | 87 (28%) | 44 (28%) |
| Race | ||||
| White | 217 (70%) | 101 (65%) | 279 (91%) | 144 (92%) |
| Black or African American | 12 (4%) | 6 (4%) | 7 (2%) | 1 (1%) |
| Asian | 70 (23%) | 42 (27%) | 9 (3%) | 3 (2%) |
| Other | 10 (3%) | 6 (4%) | 12 (4%) | 8 (5%) |
| Age | ||||
| Mean (SD) | 46.0 (13.0) | 48.0 (14.0) | 46.0 (14.0) | 46.0 (12.0) |
| Median | 48.0 | 48.0 | 44.0 | 46.0 |
| Range | 18 to 82 | 19 to 76 | 19 to 80 | 20 to 76 |
| Age Group | ||||
| 65=""> | 281 (91%) | 136 (88%) | 280 (91%) | 142 (91%) |
| ≥ 65 years | 28 (9%) | 18 (12%) | 27 (9%) | 14 (9%) |
| Country | ||||
| U.S. | 131 (42%) | 69 (45%) | 85 (28%) | 44 (28%) |
| Non-U.S. | 178 (58%) | 88 (55%) | 222 (72%) | 112 (72%) |
FDA Review
How were the trials designed?
The benefit and side effects of ILUMYA were evaluated in three clinical trials of patients with moderate to severe plaque psoriasis. Trial 1 was used for evaluation of safety only. Trials 2 and 3 were used to evaluate both, safety and benefits of ILUMYA.
In Trial 1, patients were randomly assigned to receive various ILUMYA doses or placebo for up to Week 52. Neither, the patients nor the health care providers knew which treatment was being given until after the trial was completed.
In Trials 2 and 3, patients received treatment with ILUMYA or placebo at Week 0, Week 4, and every twelve weeks thereafter up to 64 weeks. Neither, the patients nor the health care providers knew which treatment was being given until after the trial was completed. At Week 12, patients were evaluated for improvement of psoriasis by scoring the extent, nature, and severity of psoriatic changes of the skin.
How were the trials designed?
ILUMYA was studied in 3 clinical trials.
Trial 1 was a randomized, double-blind, placebo-controlled dose-ranging trial with dosing up to Week 52. This trial was primarily used for safety assessment.
Trials 2 and 3 were randomized, double-blind, placebo-controlled trials where patients received either placebo or ILUMYA (100 mg) at Week 0, Week 4, and every twelve weeks thereafter up to 64 weeks. The co-primary efficacy endpoints were the proportion of patients who achieved PASI 75 response and the proportion of subjects with a PGA score 0 (clear) or 1 (minimal) with at least a 2-point reduction from baseline at Week 12. Both trials were used to established the efficacy and safety of ILUMYA.
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.