Summary

• NAVIGATE was a phase 3, randomized, double-blind, active-comparator controlled study that evaluated the efficacy and safety of TREMFYA in patients with moderate to severe plaque psoriasis (PsO) with an inadequate response to ustekinumab. Patients receiving TREMFYA had a significantly greater number of visits from week 28 to week 40 with an Investigator’s Global Assessment (IGA) score of 0 or 1 and ≥2-grade improvement from week 16 vs patients receiving ustekinumab (P<0.001).^1-3
• In the open-label extension of VOYAGE 1, a phase 3, multicenter, randomized, double-blind, placebo and active comparator-controlled study that evaluated the efficacy and safety of TREMFYA in patients with moderate to severe plaque PsO, 73% of patients originally randomized to adalimumab at week 0 who were Psoriasis Area Severity Index 90 (PASI 90) nonresponders and were switched to TREMFYA at week 52 achieved ≥90% improvement in PASI 90 at week 100.^4,5
• A phase 3, multicenter, randomized, double-blind, placebo and active comparator-controlled study, VOYAGE 2, evaluated the efficacy and safety of TREMFYA compared to placebo and adalimumab in patients with moderate to severe plaque PsO. Of those patients originally randomized to adalimumab at week 0 who were PASI 90 nonresponders and were switched to TREMFYA at week 28, 75% achieved a PASI 90 response at week 100.^4,6
• At week 252, 82.5% (N=246) and 79.1% (N=177) of patients in the adalimumab→TREMFYA group achieved a PASI 90 response from the VOYAGE 1 and VOYAGE 2 studies, respectively.⁷
• Safety of adalimumab→TREMFYA-treated patients was further evaluated in a pooled analysis of VOYAGE 1 and VOYAGE 2 studies through week 264.⁸

CLINICAL STUDIES

NAVIGATE

Langley et al (2017)^1-3 reported results from a phase 3, randomized, double-blind, active comparator-controlled study evaluating the efficacy and safety of TREMFYA in 268 patients with moderate to severe PsO with an inadequate response to ustekinumab.

Study Design/Methods

• The study consisted of a 16 week open-label treatment period; a 28-week randomized, double-blinded, active-treatment period; and a 16-week follow-up period.
• Patients received open-label ustekinumab (weight ≤100 kg: 45 mg; weight >100 kg: 90 mg) at week 0 and week 4.
• At week 16:
  • Patients who had an IGA score of ≥2 were randomized in a double-blinded fashion to TREMFYA 100 mg at weeks 16 (12 weeks after the last dose of ustekinumab), 20, and every 8 weeks or to continue ustekinumab at week 16 and every 12 weeks (randomized group).
  • Patients who had an IGA score of 0 or 1 continued treatment with open-label ustekinumab (n=585) every 12 weeks (nonrandomized group).
• The study compared the TREMFYA and ustekinumab groups among randomized patients who had an inadequate response (IGA score of ≥2) to ustekinumab at week 16.
• The primary endpoint was the number of visits from week 28 to week 40 in which patients had an IGA score of 0 or 1 and ≥2-grade improvement from week 16.
• Secondary endpoints included the number of visits between week 28 and week 40 in which patients had a PASI 90 response or IGA 0 response, the proportions of patients achieving an IGA score of 0 or 1 and ≥2-grade improvement (from week 16) at weeks 28 and 52, and the proportions of patients achieving a PASI 90 response at weeks 28 and 52.
• Patient-reported outcomes and health-related quality of life measurements included: the proportions of patients who achieved Psoriasis Symptom & Sign Diary (PSSD) symptoms or signs score of 0 at week 52, the proportions of patients who achieved an individual PSSD symptom or sign score of 0 at week 52, the proportions of patients who achieved PSSD symptoms or signs score of 0 from week 28 through week 52, and the proportions of patients who achieved a Dermatology Life Quality Index (DLQI) score of 0 or 1 from week 16 through week 52.

Results

Patient Characteristics

• A total of 871 patients received open-label ustekinumab through week 16.
• At week 16, 30.8% of patients (n=268) had an IGA score of ≥2 and were randomized to either TREMFYA 100 mg (n=135) or ustekinumab (n=133). A total of 67.2% of patients (n=585) had an IGA score of 0 or 1 and continued open-label ustekinumab.

Efficacy

• Primary and secondary endpoints of the study are noted in Table. Results from Randomized Patients Who Had an IGA ≥2 at Week 16: Primary and Secondary Endpoints.

• At week 52, a greater proportion of randomized patients achieved a PASI 100 response in the TREMFYA-treated group vs the placebo-treated group (20.0% vs 7.5%, respectively [P=0.003]).

Patient-Reported Outcomes and Health-Related Quality of Life

• The proportions of patients who achieved (individual) PSSD symptoms or signs scores of 0 at week 52, along with the proportions of patients who achieved a DLQI score of 0 or 1 from week 16 through week 52 are detailed in Table: Results: Patient-Reported Outcomes of Psoriasis Symptoms and Signs, and Health-Related Quality of Life.

Safety

Open-Label Ustekinumab Run-In Period (Weeks 0-16)

• Adverse events (AEs) were reported in 254 (29.2%) patients receiving ustekinumab through week 16.
• The most common AEs were nasopharyngitis and upper respiratory tract infections (URTI).
• Serious adverse events (SAEs) were reported in 11 (1.3%) patients receiving ustekinumab.
• Serious infections were reported in 2 patients (pneumonia and anal abscess).
• Malignancies were reported in 2 patients (basal cell carcinoma in both).
• No opportunistic infections, active tuberculosis (TB), major adverse cardiovascular events (MACE), or deaths were reported.

Randomized TREMFYA and Ustekinumab Groups (Weeks 16-60)

• AEs were reported in 87 (64.4%) patients receiving TREMFYA and 74 (55.6%) patients receiving ustekinumab.
• The most common AEs in both randomized groups were infections (TREMFYA, 41.5%; ustekinumab, 35.3%).
• The higher overall rate of AEs in the TREMFYA group appeared to be related to a higher reported incidence of musculoskeletal and connective tissue disorders (TREMFYA, 12.6%; ustekinumab 6.8%), with a higher proportion of AEs reported with back pain and psoriatic arthropathy, and general disorders and administration site conditions (TREMFYA, 11.9%; ustekinumab, 1.5%) with the majority being injections site reactions which were all mild.
• SAEs were reported in 9 (6.7%) patients receiving TREMFYA and 6 (4.5%) patients receiving ustekinumab.
• One serious infection (bacterial arthritis) occurred in the TREMFYA group.
• No opportunistic infections or active TB were reported.
• Two malignancies (transitional cell carcinoma of the bladder and a fatal squamous cell carcinoma of the neck [origin unknown]) were reported in the TREMFYA group. The patient was diagnosed just prior to the final study visit and died 9 months later.
• Myocardial infarctions (MIs) were reported in 3 patients (TREMFYA, 2; ustekinumab, 1). All 3 patients had at least 2 known cardiovascular risk factors.
• Injections site reactions were uncommon during this period and all were mild.
• There were no anaphylactic or serum sickness-like reactions or AEs of Crohn’s disease.

Nonrandomized Open-Label Ustekinumab Continuation Group (Weeks 16-60)

• AEs were reported in 242 (41.4%) nonrandomized patients receiving ustekinumab.
• The most common AEs were nasopharyngitis and URTI.
• SAEs were reported in 20 (3.4%) of patients after week 16. These included 5 serious infections (appendicitis, epididymitis, periodontitis, paraspinal abscess each occurred in 1 patient; salpingitis and urinary tract infections, both occurred in the same patient).
• No opportunistic infections or active TB were reported.
• Malignancies were reported in 4 patients (bile duct cancer, fatal metastatic pancreatic carcinoma, basal cell carcinoma, and squamous cell carcinoma of the skin).
• One acute MI was reported in a patient with multiple known risk factors.
• One death occurred in the previous mentioned patient with metastatic pancreatic carcinoma.
• Two injections-site reactions occurred (2/1734 injections [0.1%]), neither was severe.
• No anaphylactic or serum sickness-like reactions or AEs of Crohn’s disease were reported.
• For additional safety data see Table: AEs through Week 60.

VOYAGE 1

Blauvelt et al (2017)⁵  reported results from 837 moderate to severe plaque PsO patients in a phase 3, multicenter, randomized, double-blind, placebo and active comparator-controlled study that evaluated efficacy and safety of TREMFYA in patients with moderate to severe plaque PsO. Patients originally randomized to adalimumab at week 0 were switched to TREMFYA 100 mg starting at week 52 (5 weeks after the last dose of adalimumab), then every 8 weeks thereafter as shown in Figure: VOYAGE 1 Study Design.^4,5,9

Study Design/Methods

• The responses at week 100 in patients who were adalimumab PASI 90 nonresponders at week 52 (n=138) are shown in Table: VOYAGE 1 Response Rates at Week 100 in Patients Who Were Adalimumab PASI 90 Nonresponders at Week 52.⁴

• The response at week 252 in patients who crossed over from adalimumab to TREMFYA at week 52 are shown in Table: VOYAGE 1 Response Rates at Week 252 in Patients Who Crossed Over from Adalimumab to TREMFYA at Week 52.⁷

VOYAGE 2

Reich et al (2017)⁶ reported results from 992 moderate to severe plaque PsO patients in a phase 3, multicenter, randomized, double-blind, placebo and active comparator-controlled study evaluating the efficacy and safety of TREMFYA compared to placebo and adalimumab. Other efficacy and safety assessments were conducted in patients with interrupted TREMFYA treatment, and patients who were adalimumab nonresponders who were switched to TREMFYA.

Study Design/Methods

• Eligible patients were randomized in a 2:1:1 ratio (TREMFYA [n=496]: placebo [n=248]: adalimumab [n=248]) to 1 of 3 treatment arms as shown in Figure: VOYAGE 2 Study Design.^6,10

Results

• The responses at week 100 in patients who were adalimumab PASI 90 nonresponders at week 28 (n=112) are shown in Table: VOYAGE 2 Response Rates at Week 100 in Patients Who Were Adalimumab PASI 90 Nonresponders at Week 28.⁴

• The responses at week 252 in patients from the adalimumab→TREMFYA group are shown in Table: VOYAGE 2 Response Rates at Week 252 in Patients from Adalimumab→TREMFYA Group.⁷

Safety

Randomized Withdrawal and Retreatment Period (Weeks 28-48)

• No patients discontinued treatment because of an AE during this period.⁶
• One serious infection was reported in the maintenance group.
• No additional malignancies, nonmelanoma skin cancers (NMSCs), or MACE were reported.
• There were no AEs reported among the 16 patients who were retreated.

Additional Safety Through Week 48

• Two additional NMSCs occurred in the placebo→TREMFYA group.
• One additional MACE (MI) was reported in the placebo→TREMFYA group.
• No serious infections, malignancies, or MACE occurred in the adalimumab→TREMFYA group.
• No deaths, opportunistic infections, hypersensitivities, or anaphylactic reactions occurred through week 48.
• Antibodies to guselkumab were detected in 6.6% (57/869) of patients through week 48, with generally low titers (88% ≤1:160).
• No association was observed between antibody development and decreased efficacy or injection site reaction development.

Pooled Safety Data from Adalimumab-Treated Patients in VOYAGE 1 and VOYAGE 2 through Week 264

• Event rates per 100 patient-years (PY) of follow-up at week 264 from pooled safety data of VOYAGE 1 and VOYAGE 2 are shown in Table: Event Rates Per 100 PY of Follow-up, Pooled VOYAGE 1 and VOYAGE 2 Data Through Week 264 Among Adalimumab→TREMFYA Patients.⁸

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 25 December 2024. Summarized above include moderate to severe plaque PsO data from pivotal clinical trials.