SUMMARY

• Two phase 3, multicenter, randomized, double-blind, placebo and active comparator-controlled studies, VOYAGE 1 AND VOYAGE 2, evaluated the efficacy and safety of TREMFYA compared to placebo and adalimumab in patients with moderate to severe plaque psoriasis (PsO). In both studies, significantly more patients receiving TREMFYA achieved the coprimary endpoints of an Investigator’s Global Assessment (IGA) score of cleared (0) or minimal (1) and ≥90% improvement in Psoriasis Area and Severity Index (PASI 90) response at week 16 vs placebo (P<0.001). IGA 0, IGA 0 or 1, and PASI 90 responses were also significantly higher in patients receiving TREMFYA vs adalimumab throughout the studies (P<0.001).^1,2

CLINICAL DATA

VOYAGE 1

Blauvelt et al (2016)¹ reported results from 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 837 patients with moderate to severe plaque PsO.

Study Design/Methods

• Adult patients (≥18 years of age) with a diagnosis of plaque PsO for ≥6 months who were candidates for phototherapy or systemic therapy and had a baseline IGA score ≥3, a PASI score ≥12, and ≥10% of their body surface area (BSA) involved were eligible for enrollment.
• Patients with guttate, erythrodermic, pustular, or drug-induced PsO were excluded.³
• Eligible patients were randomized in a 2:1:2 ratio (TREMFYA [n=329]: placebo [n=174]: adalimumab [n=334]) to 1 of 3 treatment arms as shown in Figure: VOYAGE 1 Study Design.

• The coprimary endpoints were the proportion of patients achieving an IGA score of cleared (0) or minimal (1) and the proportion of patients who achieved a PASI 90 response at week 16, in the TREMFYA group compared to placebo.
• Major secondary endpoints for TREMFYA vs placebo and TREMFYA vs adalimumab are listed in Table: VOYAGE 1 - Major Secondary Endpoints.

• Additional regional psoriasis efficacy assessments included: fingernail Physician Global Assessment (f-PGA); Nail Psoriasis Severity Index (NAPSI); and Physician Global Assessment of Hands and/or Feet (hf-PGA).
• In addition to the psoriasis symptoms and signs diary (PSSD), patient reported outcomes were also assessed using the Dermatology Life Quality Index (DLQI), where a score of 0 or 1 indicated no impact of PsO on health-related quality of life.
• Safety was monitored through week 48.

Results

Patient Characteristics

• Treatment discontinuation, through week 48, occurred in 6.9% (12 of 174), 8.5% (28 of 329), and 15.6% (52 of 334) of patients in the placebo, TREMFYA, and adalimumab groups, respectively.
• Demographic and disease characteristics were comparable across treatment groups at baseline.

Efficacy

• At week 16, the coprimary endpoint results of an IGA score of 0 or 1 and PASI 90 were achieved by significantly more TREMFYA patients vs placebo patients (85.1% [280/329] vs 6.9% [12/174] and 73.3% [241/329] vs 2.9% [5/174], respectively; P<0.001 for each).
• Major secondary endpoints are described in Table: IGA and PASI Response Rates for TREMFYA and Adalimumab Groups at Weeks 16, 24, and 48.
• TREMFYA was superior to placebo and/or adalimumab for the coprimary endpoints and all major secondary endpoints (P<0.001 for all).

• At week 24, PASI 75 and PASI 100 were achieved by more TREMFYA patients vs adalimumab patients (91.2% [300/329] vs 72.2% [241/334] and 44.4% [146/329] vs 24.9% [83/334]).
• At week 48, PASI 75 and PASI 100 were achieved by more TREMFYA patients vs adalimumab patients (87.8% [289/329] vs 62.6% [209/334] and 47.4% [156/329] vs 23.4% [78/334]).
• PASI responses and IGA scores were observed through week 48 in Figure: Percentage of Patients Achieving PASI 90 Response, PASI 100 Response, IGA Score of Cleared (0) or Minimal (1), and IGA Score of Cleared (0) Through Week 48 by Visit; Patients Randomized at Week 0.

Regional Psoriasis Measures

• At week 16, the proportion of patients in the TREMFYA group achieving scalp-specific IGA (ss-IGA) score 0/1 (absent/very mild scalp psoriasis) was significantly higher compared with placebo (83.4% [231/277] vs 14.5% [21/145], P<0.001).
• A better response in ss-IGA was observed at both week 24 and 48 in the TREMFYA group vs the adalimumab group (84.5% [234/277] vs 69.2% [198/286] and 78.3% [217/277] vs 60.5% [173/286]).
• At week 16, the proportion of patients achieving f-PGA score 0/1 (clear/minimal) and the percent improvement in NAPSI score were higher for TREMFYA vs placebo (39.1% [68/174] vs 15.9% [14/88] and 34.4±42.46 vs -0.9±57.89). The f-PGA response at week 48 was greater for TREMFYA vs adalimumab (74.7% [130/174] vs 61.8% [107/173]).
• The proportion of patients achieving hf-PGA score 0/1 (clear/almost clear) was higher for TREMFYA vs placebo at week 16 (73.3% [66/90] vs 14.0% [6/43]), and responses to TREMFYA were superior to adalimumab at week 24 (78.9% [71/90] vs 56.8% [54/95]) and week 48 (75.6% [68/90] vs 62.1% [59/95]).

Health-Related Quality of Life Measures

• At week 16, the improvement from baseline in DLQI score was significantly greater for TREMFYA-treated patients compared with placebo-treated patients (mean change -11.2 vs -0.6, P<0.001).
• The change in PSSD symptom score and sign score at week 16 for TREMFYA-treated patients and placebo-treated patients were -41.9±24.61and -3.0±19.56 for symptom score and -44.6±22.00 and -4.1±17.87 for sign score, respectively.
• At week 24, a DLQI score of 0 or 1 was achieved by 60.9% (195/320) of the TREMFYA-treated patients and 39.5% (126/319) of the adalimumab-treated patients. Similar results were seen at week 48 (62.5% [200/320] vs 38.9% [124/319]).
• For patients with a baseline PSSD ≥1, the proportion of patients who achieved a PSSD of 0 at week 24 was 36.3% (90/248) for the TREMFYA group and 21.6% (59/273) for the adalimumab group.

Safety

• Through week 16, the proportion of patients with at least 1 adverse events (AEs) was comparable across treatment groups (49.4% placebo, 51.7% TREMFYA, 51.1% adalimumab), and the most commonly reported events were nasopharyngitis and upper respiratory tract infection.
• Through week 48, AEs were reported at a similar rate in the TREMFYA and adalimumab groups (73.9% vs 74.5%, respectively).
• Through week 16, serious AEs (SAEs) were reported in 1.7%, 2.4%, and 1.8% of placebo-, TREMFYA-, and adalimumab-treated patients, respectively.
• Through week 48, SAEs were reported in 4.9% of TREMFYA-treated patients and 4.5% of adalimumab-treated patients.
• Serious infections occurred in 2 TREMFYA-treated patients and 3 adalimumab-treated patients, through week 48.
• Two malignancies (prostate and breast) were reported in the TREMFYA group, through week 48.
• One major adverse cardiovascular event (MACE) occurred in each of the active treatment groups (both myocardial infarction [MI]) through week 16. No additional MACE occurred through week 48.
• Through week 48, injection site reactions (ISRs) occurred in 2.2% of TREMFYA-treated patients and in 9.0% of adalimumab-treated patients. Most ISRs were mild.
• Antibodies to guselkumab were detected in 5.3% (26/492) of patients through week 44, with titers being generally low (81% ≤1:320). The occurrence of ISRs was not observed to be related to antibody development.

VOYAGE 2

Reich et al (2016)² 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

• Adult patients (≥18 years of age) with a diagnosis of plaque PsO for ≥6 months who were candidates for phototherapy or systemic therapy and had a baseline IGA score ≥3, a PASI score ≥12, and ≥10% of their BSA involved were eligible for enrollment.
• Patients with guttate, erythrodermic, pustular, or drug-induced PsO were excluded.⁵
• 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.

• The coprimary endpoints were the proportion of patients achieving an IGA of cleared (0) or minimal (1) and the proportion of patients achieving a PASI 90 response at week 16, comparing the TREMFYA and placebo groups.
• Major secondary endpoints for the TREMFYA vs placebo groups, the TREMFYA vs adalimumab groups, and the maintenance vs withdrawal groups are listed in Table: VOYAGE 2 - Major Secondary Endpoints.

• Safety was monitored through week 48.

Results

Patient Characteristics

• Overall, treatment discontinuation occurred in 9.7% (96/992) of patients (TREMFYA 7.9%; placebo 11.7%; adalimumab 11.3%) through week 48.
• Baseline demographics and disease characteristics were generally comparable among treatment groups.

Efficacy

• At week 16, the coprimary endpoints of an IGA score of 0 or 1 and PASI 90 were achieved by significantly more TREMFYA patients vs placebo patients (84.1% [417/496] vs 8.5% [21/248] and 70.0% [347/496] vs 2.4% [6/248], respectively; P<0.001 for both).
• A significantly higher PASI score percent improvement was observed at week 2 in the TREMFYA group vs the placebo group (P<0.001).
• Major secondary endpoints results are described in Table: Efficacy Measures and Patient-Reported Outcomes at Week 16 and Week 24.

• PASI responses and IGA scores were observed through week 28 in Figure: Percentage of Patients Achieving PASI 90 Response, PASI 100 Response, IGA Score of Cleared (0) or Minimal (1), or IGA Score of Cleared (0) Through Week 28 by Visit; Patients Randomized at Week 0.

Randomized Withdrawal and Retreatment Period (Week 28-48)

• During the randomized withdrawal and retreatment period (week 28-48), PASI 90 response was better maintained by the TREMFYA week-28 responders who continued TREMFYA vs those who were rerandomized to placebo.
• Among patients withdrawn from TREMFYA at week 28, PASI 90 response rates began to diverge from the maintenance group at week 32.
• The medium time to loss of PASI 90 response in patients withdrawn from TREMFYA was 15.2 weeks (23 weeks after the last TREMFYA dose).
• Through week 48, 88.6% of patients in the maintenance group sustained a PASI 90 response vs 36.8% of patients in the withdrawal group.
• Clinical responses (IGA, PASI) and improvements in DLQI and PSSD symptom or sign scores from baseline were all greater in the maintenance group than in the withdrawal group.
• Through week 48, a small number of patients (n=16) were retreated with TREMFYA due to ≥50% loss of week-28 PASI 90 response.

Safety

Placebo-controlled period (weeks 0-16):

• At least 1 AE occurred in 44.8% (111/248), 47.6% (235/494), and 48.4% (120/248) of patients in the placebo, TREMFYA, and adalimumab groups, respectively.
• The most commonly reported AEs were nasopharyngitis, headache, and upper respiratory tract infection.
• The rates of infections, infections requiring treatment and serious infections were similar among the groups.
• No malignancies or nonmelanoma skin cancers (NMSC) were reported.
• One MACE (MI) occurred in the adalimumab group.
• ISRs occurred in 6.9% of adalimumab-treated patients vs 2.6% of TREMFYA-treated patients.

Active-comparator period (weeks 0-28):

• The proportion of patients with 1 or more AE, AEs leading to discontinuation, and SAEs were comparable between the TREMFYA and adalimumab groups (58.3% vs 62.9%, 2.2% vs 2.4%, and 3.6% vs 3.6%, respectively).
• Infections and infections requiring treatment were also comparable between TREMFYA and adalimumab groups.
• Three serious infections were reported in both the TREMFYA and adalimumab groups and 1 serious infection was reported in the placebo→TREMFYA group.
• One malignancy and 1 NMSC were reported in the TREMFYA group and 2 NMSCs were reported in the placebo→TREMFYA group.²
• One MACE (MI) was reported in each of the TREMFYA and adalimumab groups.

Randomized withdrawal and retreatment period (weeks 28-48):

• No patients discontinued treatment because of an AE during this period.
• One serious infection was reported in the maintenance group.
• No additional malignancies, NMSC, 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.²
• 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 ISR development.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 06 May 2024.

Summarized in this response are relevant clinical data from VOYAGE 1 and VOYAGE 2 studies.