SUMMARY

• Please refer to local labeling for relevant information on hypersensitivity reactions.
• No systemic hypersensitivity reactions, including anaphylactic reactions or serum sickness-like reactions, were reported through week 264 in the VOYAGE 1 study, a phase 3, multicenter, randomized, double-blind, placebo and active comparator study evaluating the efficacy and safety of TREMFYA compared to placebo and adalimumab in patients with moderate to severe plaque psoriasis (PsO).¹
• Through week 264 in the VOYAGE 2 study, 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 in patients with moderate to severe plaque PsO, 1 patient reported an anaphylactic reaction to metamizole, which was considered unrelated to study agent, while being treated for an adverse event of herpes zoster.²
• No hypersensitivity reactions were reported in either the TREMFYA or ustekinumab  treatment groups in the NAVIGATE study, a phase 3, randomized, double-blind, active-comparator controlled study evaluating the efficacy and safety of TREMFYA compared to ustekinumab in patients with moderate to severe plaque PsO with an inadequate response to ustekinumab, through week 60.³
• One patient in the combined TREMFYA arm (N=75) reported a serious adverse event of drug hypersensitivity and no patients reported anaphylactic/serum sickness-like reactions through week 40 in the ORION study, a phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy, safety, and pharmacokinetics of TREMFYA compared to placebo, both administered via the One-Press patient-controlled injection device.⁴
• No serum sickness-like or anaphylactic reactions related to TREMFYA were reported in a pooled safety analysis across 7 plaque PsO trials (X-PLORE, VOYAGE 1, VOYAGE 2, NAVIGATE, ORION, ECLIPSE, Japan registration).⁵
• In two phase 3, multicenter, randomized, double-blind, placebo-controlled studies evaluating the efficacy and safety of TREMFYA in adults with active psoriatic arthritis, DISCOVER-1 and DISCOVER-2, no anaphylactic or serum sickness-like reactions were reported through week 60 and week 112, respectively.^6,7
• No serum sickness-like or anaphylactic reactions related to TREMFYA were reported in an integrated pooled safety analysis from 11 phase 2 and 3 clinical trials in patients with plaque PsO and active PsA (X-PLORE, VOYAGE 1, VOYAGE 2, NAVIGATE, ORION, ECLIPSE, Japan registration, Phase 2 PsA study, DISCOVER 1, DISCOVER 2, COSMOS).⁸
• Serious hypersensitivity reactions, including anaphylaxis, have been reported in the postmarketing setting. Some serious hypersensitivity reactions occurred several days after treatment with TREMFYA, including cases with urticaria and dyspnea.⁹

CLINICAL trial DATA – Moderate to Severe plaque psoriasis

VOYAGE 1

Study Design/Methods

• Patients were randomized 2:1:2 to:¹⁰
  • TREMFYA 100 mg at weeks 0 and 4, then every 8 weeks (q8w; n=329)
  • Placebo through week 16, then TREMFYA 100 mg at weeks 16 and 20, then q8w (n=174)
  • Adalimumab 80 mg at week 0, 40 mg at week 1, then every 2 weeks (q2w; n=334)
• All patients received open-label TREMFYA 100 mg q8w from week 52 through week 252 (5 years).
• Safety was assessed through week 264.

Results

• No anaphylactic or serum sickness-like reactions were reported through week 264 in the VOYAGE 1 study, a phase 3, multicenter, randomized, double-blind, placebo and active comparator study evaluating the efficacy and safety of TREMFYA compared to placebo and adalimumab in patients with moderate to severe plaque PsO.¹

VOYAGE 2

Study Design/Methods

• Patients were randomized 2:1:1 to:¹⁰
  • TREMFYA 100 mg at weeks 0 and 4, then q8w (n=496)
  • Placebo through week 16, then TREMFYA 100 mg at weeks 16 and 20, then q8w (n=248)
  • Adalimumab 80 mg at week 0, 40 mg at week 1, then q2w (n=248)
• At week 28:
  • TREMFYA-treated patients who achieved ≥90% improvement in Psoriasis Area and Severity Index (PASI 90) (responders) were rerandomized in a 1:1 ratio to TREMFYA or placebo, and upon loss of 50% or more of their week-28 PASI 90 response were retreated with TREMFYA, another dose 4 weeks later, then q8w thereafter. TREMFYA nonresponders continued TREMFYA treatment.
  • Placebo→TREMFYA responders received placebo q8w beginning at week 28, and upon loss of 50% or more of their week-28 PASI 90 response were retreated with TREMFYA, another dose 4 weeks later, then q8w thereafter. Placebo→TREMFYA nonresponders at week 28 continued TREMFYA q8w.
  • Adalimumab responders received placebo and upon loss of 50% or more of week 28 PASI 90 response, initiated TREMFYA, another dose 4 weeks later, then q8w thereafter, and adalimumab nonresponders initiated TREMFYA at week 28 (5 weeks after the last dose of adalimumab), another dose 4 weeks later, then q8w thereafter.
• All patients received open-label TREMFYA 100 mg q8w from week 76 through week 252 (5 years).
• Safety was assessed through week 264.

Results

• Though week 264, 1 patient reported an anaphylactic reaction to metamizole, which was considered not related to study agent, while being treated for an adverse event of herpes zoster.²

NAVIGATE

Study Design/Methods

• A total of 871 patients received open-label ustekinumab (45 mg [patients weighing ≤100 kg] or 90 mg [patients weighing >100 kg]) at weeks 0 and 4.³
• At week 16, patients with an inadequate response to ustekinumab (Investigator’s Global Assessment [IGA] score ≥2) were randomized to:
  • TREMFYA 100 mg at weeks 16, 20, and q8w thereafter through week 44 (n=135)
  • Continue ustekinumab at week 16 and every 12 weeks thereafter through week 40 (n=133)
• Patients with an IGA of 0 or 1 continued receiving open-label ustekinumab at week 16 and every 12 weeks thereafter through week 40 (n=585).

Results

• No hypersensitivity reactions were reported in either the TREMFYA or ustekinumab treatment groups in the NAVIGATE study, a phase 3, randomized, double-blind, active-comparator controlled study evaluating the efficacy and safety of TREMFYA compared to ustekinumab in patients with moderate to severe plaque PsO with an inadequate response to ustekinumab, through week 60.³

ORION

Study Design/Methods

• Eligible patients were randomized in a 4:1 ratio to receive SC TREMFYA 100 mg at weeks 0, 4, 12, 20, and 28 (N=62) or SC placebo at weeks 0, 4, and 12 with crossover to TREMFYA 100 mg at weeks 16, 20 and 28 (N=16), both delivered by the One-Press patient-controlled injection device. Patients randomized to TREMFYA received placebo at week 16 to maintain the blinding.⁴
• Efficacy was evaluated every 4 weeks through week 32 and again at week 40.
• Safety was assessed continuously through week 40.

Results

• One patient in the combined TREMFYA arm (N=75) reported a serious adverse event of drug hypersensitivity and no patients reported anaphylactic/serum sickness-like reactions through week 40 in the ORION study, a phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy, safety, and pharmacokinetics of TREMFYA compared to placebo, both administered via the One-Press patient-controlled injection device.⁴

CLINICAL DATA – ACTIVE PSORIATIC ARTHRITIS

DISCOVER-1 and DISCOVER-2

Study Design/Methods

• In DISCOVER-1, approximately 31% of patients were previously treated with up to 2 tumor necrosis factor inhibitor (TNFi) agents whereas in DISCOVER-2, all patients were biologic-naive.^11,12
• Patients in the studies were randomized 1:1:1 to:
  • TREMFYA 100 mg at week 0 and 4, then q8w
  • TREMFYA 100 mg at week 0, then every 4 weeks (q4w) or
  • Placebo through week 20, then TREMFYA 100 mg at week 24, then q4w
• Safety was assessed through week 60 for DISCOVER-1 and through week 112 for DISCOVER-2.^6,7

Results

• No anaphylactic or events of serum sickness (including serum sickness-like reactions) were reported through week 60 and through week 112 in DISCOVER-1 and in DISCOVER-2, respectively.^6,7

Literature Search

A literature search of MEDLINE^®, Embase, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 11 November 2024.

Data included in this response are from the following phase 3 clinical trials of TREMFYA in patients with plaque psoriasis or psoriatic arthritis (VOYAGE 1, VOYAGE 2, NAVIGATE, ORION, DISCOVER 1, DISCOVER 2). Additional information from relevant pooled safety analyses across PsO and/or active PsA are also included.