Drug Trials Snapshots: TREMFYA
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 TREMFYA Prescribing Information for complete information.
Tremfya (guselkumab)
trem fye´ ah
Janssen Biotech, Inc.
Approval date: July 13, 2017
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
TREMFYA 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?
TREMFYA is an injection given under the skin. First two injections are given 4 weeks apart followed by an injection once every eight weeks.
What are the benefits of this drug (results of trials used to assess efficacy)?
TREMFYA was better than a placebo in improving symptoms of plaque psoriasis and maintaining the improvement through a year of treatment.
What are the benefits of this drug (results of trials used to assess efficacy)?
The table below summarizes efficacy results for the clinical trials based on the two co-primary endpoints: 1) the proportion of subjects with a Physicians Global Assessment (PGA) score of 0 (clear) or 1 (almost clear), and 2) PASI 90, the proportion of subjects who achieved at least a 90% reduction in the Psoriasis Area and Severity Index (PASI) composite score that takes into consideration both the percentage of body surface area affected and the nature and severity of psoriatic changes (induration, erythema, and scaling) within the affected region. Results are presented using ITT (Intent to Treat) population.
Table 2. Efficacy Results at Week 16 in Adults with Plaque Psoriasis in Trials 1 and 2; NRIa
| Trial 1 | Trial 2 | |||||
|---|---|---|---|---|---|---|
| Endpoint | TREMFYA (N=329) n (%) |
Placebo (N=174) n (%) |
TREMFYA (N=496) n (%) |
Placebo (N=248) n (%) |
||
| IGA response of 0/1b, c | 280 (85) | 12 (7) | 417 (84) | 21 (8) | ||
| PASI 90 responseb | 241 (73) | 5 (3) | 347 (70) | 6 (2) | ||
a Non-Responder Imputation
b Co-primary endpoints
c IGA response of 0(clear) or 1 (minimal)
PASI= Psoriasis Area and Severity Index
TREMFYA Prescribing Information
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
- Sex: TREMYFA 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 efficacy results by subgroup for each trial based on co-primary endpoints.
Figure 4. IGA Score of 0 or 1 at Week 16 by Sex, Race, and Age, for Trial 1
n[T]= number of patients in TREMFYA subgroup; n[P] number of patients in placebo subgroup
Adapted from FDA Statistical review
Figure 5. PASI 90 Response at Week 16 by Sex, Race, and Age, for Trial 1
n[T]= number of patients in TREMFYA subgroup; n[P] number of patients in placebo subgroup
Adapted from FDA Statistical review
Figure 6. IGA Score of 0 or 1 at Week 16 by Sex, Race, and Age, for Trial 2
n[T]= number of patients in TREMFYA subgroup; n[P] number of patients in placebo subgroup
Adapted from FDA Statistical review
Figure 7. PASI 90 Response at Week 16 by Sex, Race, and Age, for Trial 2
n[T]= number of patients in TREMFYA subgroup; n[P] number of patients in placebo subgroup
Adapted from FDA Statistical review
What are the possible side effects?
TREMFYA may cause serious infections. Before starting TREMFYA, patients should be evaluated for tuberculosis infection.
The most common side effects of TREMFYA are upper respiratory tract infections, headache, injection site reactions, joint pain, diarrhea, stomach flu, fungal skin infections and herpes simplex infections.
What are the possible side effects (results of trials used to assess safety)?
The table below summarizes the most common adverse reactions that occurred in clinical trials. The results are based on safety population defined as all patients in the trials who received at least one dose of trial drug.
Table 3. Adverse Reactions Occurring in ≥1% of Patients through Week 16 in Trials 1 and 2
| TREMFYAa N=823 n (%) |
Adalimumabb N=196 n (%) |
Placebo N=422 n (%) |
|
|---|---|---|---|
| Upper respiratory infectionsc | 118 (14.3) | 21 (10.7) | 54 (12.8) |
| Headached | 38 (4.6) | 2 (1.0) | 14 (3.3) |
| Injection site reactionse | 37 (4.5) | 15 (7.7) | 12 (2.8) |
| Arthralgia | 22 (2.7) | 4 (2.0) | 9 (2.1) |
| Diarrhea | 13 (1.6) | 3 (1.5) | 4 (0.9) |
| Gastroenteritisf | 11 (1.3) | 4 (2.0) | 4 (0.9) |
| Tinea infectionsg | 9 (1.1) | 0 | 0 |
| Herpes simplex infectionsh | 9 (1.1) | 0 | 2 (0.5) |
a patients receiving 100 mg of TREMFYA at Week 0, Week 4, and every 8 weeks thereafter
b U.S. licensed adalimumab
c Upper respiratory infections include nasopharyngitis, upper respiratory tract infection (URTI), pharyngitis, and viral URTI
d Headache includes headache and tension headache.
e Injection site reactions include injection site erythema, bruising, hematoma, hemorrhage, swelling, edema, pruritus, pain, discoloration, induration, inflammation, and urticaria.
f Gastroenteritis includes gastroenteritis and viral gastroenteritis.
g Tinea infections include tinea pedis, tinea cruris, tinea infection, and tinea manuum infections.
h Herpes simplex infections include oral herpes, herpes simplex, genital herpes, genital herpes simplex, and nasal herpes simplex.
TREMFYA Prescribing Information
Were there any differences in side effects among 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 figure below summarizes treatment emergent adverse events (TEAEs) by subgroup for the pooled clinical trials.
Figure 8. Subgroup Analysis of TEAEs- Trials 1 and 2
Adapted from FDA review
WHO WAS IN THE STUDIES?
Who participated in the clinical trials?
The FDA approved TREMYFA based on evidence from two clinical trials of 1829 patients with moderate to severe psoriasis. The trials were conducted in the USA, Canada, Europe, Russia, Australia, Korea, and Taiwan.
The figure below summarizes how many men and women were enrolled in the clinical trials.
Figure 1. Baseline Demographics by Sex
FDA Review
Figure 2 and Table 1 below summarize the percentage of patients by race enrolled in the clinical trials.
Figure 2. Baseline Demographics by Race
FDA Review
Table 1. Baseline Demographics by Race
| Race | Number of Patients | Percentage |
|---|---|---|
| White | 1498 | 82 |
| Asian | 257 | 14 |
| Black or African American | 36 | 2 |
| Other | 38 | 2 |
Figure 3 summarizes the percentage of patients by age enrolled in the clinical trials.
Figure 3. Baseline Demographics by Age
FDA Review
Who participated in the trials?
The table below summarizes demographics of randomized patients in the clinical trials.
Table 4. Baseline Demographics of Randomized Patients in Clinical Trials
| Trial 1 | Trial 2 | |||||
|---|---|---|---|---|---|---|
| Demographic Parameter | TREMFYA (N=329) |
Adalimumab* (N=334) |
Placebo (N=174) |
TREMFYA (N=496) |
Adalimumab* (N=248) |
Placebo (N=248) |
| Age (years) | ||||||
| Mean (SD) | 44 (13) | 43 (13) | 45 (13) | 44 (12) | 43 (12) | 43 (12) |
| Median | 43 | 43 | 45 | 44 | 43 | 43 |
| Range | 19 – 76 | 18 – 87 | 19 – 77 | 18 – 74 | 19 – 70 | 18 – 71 |
| 18-64 | 311 (95%) | 318 (95%) | 164 (94%) | 473 (95%) | 237 (96%) | 239 (96%) |
| ≥ 65 | 18 (5%) | 16 (5%) | 10 (6%) | 23 (5%) | 11 (4%) | 9 (4%) |
| Sex | ||||||
| Men | 240 (73%) | 249 (75%) | 119 (68%) | 349 (70%) | 170 (69%) | 173 (70%) |
| Women | 89 (27%) | 85 (25%) | 55 (32%) | 147 (30%) | 78 (31%) | 75 (30%) |
| Race | ||||||
| White | 262 (80%) | 277 (83%) | 145 (83%) | 408 (82%) | 200 (81%) | 206 (83%) |
| Black or African American | 6 (2%) | 8 (2%) | 3 (2%) | 6 (1%) | 5 (2%) | 8 (3%) |
| Asian | 51 (15%) | 47 (14%) | 23 (13%) | 72 (15%) | 37 (15%) | 27 (11%) |
| Other | 10 (3%) | 2 (1%) | 3 (2%) | 10 (2%) | 6 (2%) | 7 (3%) |
| Ethnicity | ||||||
| Hispanic or Latino | 16 (5%) | 30 (9%) | 19 (11%) | 27 (5%) | 13 (5%) | 12 (5%) |
| Not Hispanic or Latino | 309 (94%) | 297 (89%) | 153 (88%) | 460 (93%) | 233 (94%) | 234 (94%) |
| Unknown | 2 (1%) | 3 (1%) | 0 | 1 (<> | 0 | 0 |
| Not reported | 2 (1%) | 4 (1%) | 2 (1%) | 8 (2%) | 2 (1%) | 2 (1%) |
| Country | ||||||
| US | 65 (20%) | 67 (20%) | 38 (22%) | 93 (19%) | 48 (19%) | 49 (20%) |
| Non-US | 264 (80%) | 267 (80%) | 136 (77%) | 403 (81%) | 200 (81%) | 199 (80%) |
* U.S. licenced adalimumab and EU approved adalimumab
Adapted from FDA Review and Clinical Trial Report
How were the trials designed?
The benefit and side effects of TREMFYA were evaluated in two clinical trials of patients with moderate to severe psoriasis. Patients received one of the three treatments: TREMFYA, placebo or drug approved for psoriasis called adalimumab. Neither the patients nor the health care providers knew which treatment was being given until after the benefit was evaluated.
Patients were evaluated for improvement of psoriasis after 16 weeks of treatment by scoring of the extent, nature and severity of psoriatic changes of the skin. Some patients who achieved success with TREMFYA at Week 16 continued the treatment for 12 months to determine how long the benefit would last.
How were the trials designed?
The safety and efficacy of TREMFYA were established in two randomized, double-blind, placebo and active (US licensed adalimumab) controlled trials (Trials 1 and 2).
All patients had moderate to severe plaque psoriasis defined as a minimum body surface area involvement of 10%, a Physician Global Assessment (PGA) score of ≥3, a Psoriasis Area and Severity Index (PASI) score ≥12, and were candidates for phototherapy or systemic therapy.
The primary efficacy outcome measures were the co-primary endpoints of PASI 90 and PGA of “0” (clear) or “1” (minimal) at Week 16.
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