SUMMARY

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• Please refer to local labeling for relevant information regarding TREMFYA and the occurrence of infections.
• In a pooled analyses of patients with moderate to severe plaque psoriasis (PsO) from the VOYAGE 1 and VOYAGE 2 studies, the overall incidence of infections ranged from 56.8 to 62.0 per 100 patient-years (PY) of follow-up through week 264 across all treatment groups (TREMFYA [includes patients randomized to TREMFYA and to placebo at baseline who crossed over and were treated with TREMFYA at week 16], adalimumab (ADA)→TREMFYA [includes patients randomized to ADA], and combined TREMFYA [includes both TREMFYA and ADA→TREMFYA]).¹
• In the NAVIGATE study of patients with moderate to severe plaque PsO, infections occurred in 56 (41.5%) TREMFYA-treated patients from week 16 to week 60.²
• In the ORION study of patients with moderate to severe plaque PsO, infections occurred in 19.4% of TREMFYA patients (N=62) through week 16 and 33.3% of TREMFYA patients (N=75) through week 40.³
• In a pooled analyses of patients with active psoriatic arthritis (PsA) from the DISCOVER 1 and DISCOVER 2 studies through week 60 and week 52, respectively, the number of infections reported in patients with ≥1 infection from the combined TREMFYA group (included patients treated in the TREMFYA 100 mg every 8 weeks [Q8W] and 100 mg every 4 weeks [Q4W] groups [including those who crossed over from placebo]) through 1 year was 39.2 per 100 PY (95% confidence interval [CI], 35.0-43.8).⁴
• In a long-term safety analysis of patients with PsA from DISCOVER-2 through week 112, the incidence of infections was 37.3 per 100 PY (95% CI, 34.1-40.6) in all TREMFYA-treated patients (includes all patients who received ≥1 administration of TREMFYA, including those who crossed over from placebo at week 24).⁵
• In the COSMOS study of patients with active PsA with inadequate response to tumor necrosis factor inhibitors (TNFi), the incidence of infections was 37.2 per 100 PY (95% CI, 30.1-45.5) in all TREMFYA-treated patients (includes all patients who received ≥1 administration of TREMFYA, including those randomized to placebo).⁶
• An integrated pooled safety analysis evaluated the incidence rates of infections from 11 phase 2 and 3 clinical trials in patients with PsO and PsA.⁷
  • During a placebo-controlled period, the exposure-adjusted incidence rates (EAIR) of infections was 76.0 per 100 PY in the combined-TREMFYA group (N=2257). Through the end of the reporting period, EAIR of infections was 61.2 per 100 PY in the all TREMFYA group (N=4399).⁷

CLINICAL TRIAL DATA - moderate to severe plaque psO

VOYAGE 1

Blauvelt et al (2017)⁸ and Griffiths et al (2020)⁹ evaluated the safety and efficacy of TREMFYA in VOYAGE 1, a phase 3, randomized, double-blind, placebo- and ADA comparator-controlled study in patients with moderate to severe plaque PsO.

Study Design/Methods

• Patients were randomized 2:1:2 to:
  • TREMFYA 100 mg at weeks 0 and 4, then Q8W (n=329)
  • Placebo through week 16, then TREMFYA 100 mg at weeks 16 and 20, then Q8W (n=174)
  • ADA 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).
  • The TREMFYA group (n=494) included patients randomized to TREMFYA at baseline (n=329) and to placebo who crossed over and were treated with TREMFYA at week 16 (n=165).
  • The ADA→TREMFYA group (n=280) included patients randomized to ADA at baseline who crossed-over and were treated with TREMFYA at or after week 28.
  • The combined TREMFYA group (n=774) included both TREMFYA and ADA→TREMFYA groups, as defined above.

Results

• Incidence of infections through week 48 are presented in Table: Incidence of Infections through Week 48 - VOYAGE 1.
• During the placebo-controlled period (weeks 0-16), 2 patients in the ADA group experienced serious infections (both cellulitis).
• Between weeks 16 and 48, serious infections were reported in 2 patients in the TREMFYA group (thigh abscess and cellulitis with postoperative wound infection) and
  2 patients in the ADA group (abdominal abscess and staphylococcal pneumonia with a fatal outcome).
• Through week 264, a total of 357 patients (72.3%) in the combined TREMFYA group and 190 patients (67.9%) in the ADA→TREMFYA group experienced ≥1 infection.⁹
• A total of 188 patients (38.1%) in the combined TREMFYA group and 101 patients (36.1%) in the ADA→TREMFYA group experienced ≥1 infection requiring antibiotics through week 264.
• A total of 18 patients (3.6%) in the combined TREMFYA group and 4 patients (1.4%) in the ADA→TREMFYA group experienced ≥1 serious infection through week 264.

VOYAGE 2

Reich et al (2017)¹⁰ and Reich et al (2021)¹¹ evaluated the safety and efficacy of TREMFYA in VOYAGE 2, a phase 3, randomized, double-blind, placebo- and ADA comparator-controlled study in patients with moderate to severe plaque PsO.

Study Design/Methods

• Patients were randomized 2:1:1 to:
  • 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)
  • ADA 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.
  • ADA 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 ADA nonresponders initiated TREMFYA at week 28 (5 weeks after the last dose of ADA), 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).¹¹
  • The TREMFYA group (n=727) included patients randomized to TREMFYA at baseline and to placebo who crossed over and were treated with TREMFYA at week 16 (n=165).
  • The ADA→TREMFYA group (n=220) included patients randomized to ADA at baseline who crossed-over and were treated with TREMFYA at or after week 28.
  • The combined TREMFYA group (n=947) included both TREMFYA and ADA→TREMFYA groups, as defined above.

Results

• Incidence of infections through week 48 are presented in Table: Incidence of Infections through Week 48 - VOYAGE 2.
• During the active-comparator period (weeks 0-28), 3 serious infections each were reported in the TREMFYA (bronchitis, erysipelas, and soft-tissue infection) and ADA (2 cases of tuberculosis [TB; 1 disseminated], and 1 injection-site abscess) groups.
• From weeks 28-48 (randomized withdrawal and retreatment period), 1 serious infection (appendicitis) was reported in the maintenance group.
• Between weeks 28-48, no events of serious infections occurred in the ADA→TREMFYA group.
• No opportunistic infections (OIs) occurred through week 48.
• Through week 264, a total of 485 patients (66.7%) in the TREMFYA group and 151 patients (68.6%) in the ADA→TREMFYA group experienced ≥1 infection.¹¹
• A total of 297 patients (40.9%) in the TREMFYA group and 83 patients (37.7%) in the ADA→TREMFYA group experienced ≥1 infection requiring antibiotics through week 264.
• Twenty-three patients (3.2%) in the TREMFYA group and 5 patients (2.3%) in the ADA→TREMFYA group experienced ≥1 serious infection through week 264.

Pooled Safety Data from VOYAGE 1 and VOYAGE 2 through 5 Years

Blauvelt et al (2021)^12,13 and Langley et al (2021)¹ conducted a pooled safety analyses of VOYAGE 1 and VOYAGE 2 through week 264 (5 years).

• Through week 252, 78.4% (1349/1721) completed treatment with study drug.¹
• The incidence of infections, serious infections and common types of serious infections reported in TREMFYA-treated patients per 100 PY of follow-up through week 264 are summarized in Table: Incidence of Infections, Serious Infections, and Common Types of Serious Infections per 100 PY of Follow-Up Across Pooled VOYAGE 1 and VOYAGE 2 Data of Patients Treated with TREMFYA through Week 264.

• Incidence of infections per 100 PY of follow-up by year are summarized across pooled VOYAGE 1 and VOYAGE 2 data for patients in the combined TREMFYA group (see Table: Pooled VOYAGE 1 and VOYAGE 2 Incidence of Infections in TREMFYA-Treated Patients per 100 PY of Follow-Up by Year).

• Incidence of the most common types of infections (≥2.0 per 100 PY in any group) are summarized in Table: Incidence of the Most Common Types of Infections per 100 PY of Follow-up Across Pooled VOYAGE 1 and VOYAGE 2 Data through Week 264.

• Treatment-emergent adverse events of interest including Candida and herpes zoster infections are summarized in Table: Incidence of Candida, Herpes Zoster, and Herpes Zoster Oticus Infections per 100 PY of Follow-up Across Pooled VOYAGE 1 and Voyage 2 Data through Week 264.
• The most common Candida infections reported in the TREMFYA group were vulvovaginal candidiasis (0.29 per 100 PY; 95% CI, [0.16 to 0.47]) and skin candida infections (0.11 per 100 PY; 95% CI, [0.04 to 0.25]).¹

NAVIGATE

Langley et al (2017)² reported results from NAVIGATE, a phase 3 study to evaluate the safety and efficacy of TREMFYA in patients with moderate to severe plaque PsO with an inadequate response to ustekinumab.

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.
• 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

• Incidence of infections through week 60 are presented in Table: Incidence of Infections through Week 60 - NAVIGATE.
• AEs in the open-label ustekinumab run-in group (week 0-week 16):
  • Two patients reported a serious infection (pneumonia and anal abscess).
  • No OIs or cases of active TB occurred through week 16.
• AEs in the randomized TREMFYA and ustekinumab groups (weeks 16-60):
  • Infections were the most common AEs in both the randomized TREMFYA and ustekinumab groups.
  • One serious infection occurred (bacterial arthritis in the TREMFYA group).
  • No OIs or cases of active TB were reported.
• AEs in the nonrandomized open-label ustekinumab continuation group (weeks 16-60):
  • The most common AEs in the nonrandomized ustekinumab group were nasopharyngitis and upper respiratory tract infections.
  • Five patients in this group had a serious infection after week 16 (appendicitis, epididymitis, periodontitis, and paraspinal abscess each occurred in 1 patient; salpingitis and urinary tract infection both occurred in the same patient).
  • There were no OIs or cases of active TB.

ORION

Ferris et al (2019)³ reported results from 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.

Study Design/Methods

• Adult patients (≥18 years of age) with a diagnosis of moderate to severe PsO for≥6 months who were candidates for phototherapy or systemic therapy and had a baseline IGA score ≥3, a PASI score ≥12, and a body surface area involvement of ≥10% were eligible for enrollment.
• Patients with a history or current signs of severe, progressive, or uncontrolled medical condition or history of, or current, malignancy (exclusive of nonmelanoma skin cancer) were excluded.
• Eligible patients were randomized in a 4:1 ratio to receive subcutaneous (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.
• Efficacy was evaluated Q4W through week 32 and again at week 40.
• Safety was assessed continuously through week 40.
• The co-primary endpoints were the proportions 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.
• Major secondary endpoints, also assessed at week 16, were the proportions of patients achieving IGA 0 (cleared) and PASI 100 responses.

Results

• Infections occurred in 19.4% of TREMFYA patients (N=62) and 6.3% of placebo-treated patients (N=16) through week 16 and 33.3% of TREMFYA patients (N=75) through week 40.
• At week 16, the proportion of patients requiring antimicrobial treatment was 9.7% of TREMFYA-treated patients (N=52) and 6.3% of placebo-treated patients (N=16).
• One serious infection (diverticulitis) occurred in a TREMFYA-treated patient through week 40.
• No cases of active TB or OIs were reported through week 40.

CLINICAL TRIAL DATA - active pSoriatic arthritis

DISCOVER-1 and DISCOVER-2

Rahman et al (2021)⁴ reported pooled safety results for TREMFYA in adult patients with active PsA through 1 year of two phase 3, randomized, controlled studies (DISCOVER-1 and DISCOVER-2).

Study Design/Methods

• Patients included were adults with active PsA despite previous therapy with nonbiologic disease modifying antirheumatic drugs (DMARDs), apremilast, and/or nonsteroidal anti-inflammatory drugs.
  • In DISCOVER-1, patients were required to have ≥3 swollen joints, ≥3 tender joints, and a C-reactive protein (CRP) level ≥0.3 mg/dL.
  • In DISCOVER-2, patients were required to have ≥5 swollen joints, ≥5 tender joints, and a CRP level ≥0.6 mg/dL.
• All patients were biologic-naïve, except for approximately 30% of patients in DISCOVER-1 who were previously treated with up to 2 TNFi.
• Patients in the studies were randomized 1:1:1 to receive:
  • TREMFYA 100 mg at week 0 and 4, then Q8W (n=375).
  • TREMFYA 100 mg at week 0, then Q4W (n=373).
  • Placebo through week 20, then TREMFYA 100 mg at week 24, then Q4W (n=372).
• Safety for TREMFYA was evaluated through week 60 in DISCOVER-1 and week 52 in DISCOVER-2 based on AEs, clinical laboratory test results (classification of abnormalities based on the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE] grade), physical examinations, vital signs, concomitant medications, and screening for TB.

Results

• Incidence of infection AEs through week 24 are presented in Table: Summary of Incidence of Infections through Week 24 - Integrated Safety Results from DISCOVER-1 and DISCOVER-2.
  • In DISCOVER-1, serious infections were not reported in the TREMFYA-treated group and occurred in 2 (2%) of 126 patients in the placebo group (limb abscess and upper respiratory tract infection).¹⁴
  • In DISCOVER-2, serious infections occurred in 3 (1%) of 245 patients receiving TREMFYA Q4W (acute hepatitis B [de novo], influenza pneumonia, and oophoritis), 1 (<1%) of 248 patients receiving TREMFYA Q8W (pyrexia, probably of urinary origin), and 1 (<1%) of 246 patients in the placebo group (post-procedural fistula).¹⁵
  • No OIs or cases of active TB occurred through week 24.^12,13,16

• Incidences of infections per 100 PY through 1 year are presented in Table: Summary of the Number of Infections Per 100 PY through 1 Year - Pooled Safety Results from DISCOVER-1 and DISCOVER-2.
• The most common AEs reported in TREMFYA-treated patients (n=1100), including those who crossed over from placebo at week 24 through 1 year, were infections (nasopharyngitis, 8.4%; upper respiratory infections, 7.1%; and bronchitis, 3.4%).
• There were no safety signals for TB and OIs through 1 year.
  • Nonserious oral thrush was reported in 1 TREMFYA-treated patient who had a history of asthma and concomitant inhalational corticosteroid use.

DISCOVER-2

McInnes et al (2022)⁵ evaluated the long-term safety of TREMFYA in patients with PsA through 2 years (through week 112).

• Through 2 years, infections were the most common type of AE reported in TREMFYA-treated patients, and the most common infections were upper respiratory tract infections (8.5%) and nasopharyngitis (7.5%).
• The incidence of infections and serious infections reported through 2 years in the DISCOVER-2 study are reported in Table: DISCOVER-2: Incidence of Infection and Serious Infection through 2 Years.

• Among all TREMFYA-treated patients that reported a serious infection (n=21), 6 patients reported pneumonia (Q4W, n=2; Q8W, n=3; placebo→TREMFYA, n=1), and two had diverticulitis (Q4W, n=1 with perforation; Q8W, n=1).
  • Other serious infections that were reported include acute hepatitis B and oophoritis (Q4W); appendicitis, herpes zoster, cystitis, one patient with bacterial vaginosis and trichomoniasis, and one patient with pyrexia and urinary tract infection (Q8W); and acute hepatitis C, bacterial meningitis, costochondritis, dengue fever, infective periostitis, influenza, pericarditis, and tracheitis (placebo→TREMFYA).
• After week 52, 3 TREMFYA-treated patients experienced OIs including fungal esophagitis (concomitant methotrexate; long-standing history of gastroesophageal reflux disease and recent course of antibiotics) and herpes zoster disseminated (no concomitant DMARDs; history of diabetes and no zoster vaccination) in the Q8W group and meningitis listeria in the placebo→TREMFYA group.
• No patients developed active TB.

COSMOS

Coates et al (2022)⁶ reported the results of a phase 3b, randomized, double-blind, placebo-controlled study that assessed the efficacy and safety of TREMFYA through 1 year in patients with PsA with an inadequate response to TNFi.

Study Design/Methods

• Adult patients with active PsA (according to the ClASsification criteria for Psoriatic ARthritis [CASPAR]; ≥3 swollen joints and ≥3 tender joints), active (≥1 psoriatic plaque of ≥2 cm) or a documented history of plaque PsO or current nail PsO, and who had shown a lack of benefit or intolerance to 1-2 TNFi were included.
• At week 0, patients were randomized 2:1 to receive:
  • TREMFYA 100 mg SC at weeks 0 and 4, then Q8W through week 44.
  • Placebo at weeks 0, 4, 12, and 20, followed by TREMFYA 100 mg at weeks 24, 28, 36, and 44.
• Safety assessments were done through week 56.

Results

• Through week 24, the most common AEs in patients randomized to TREMFYA were nasopharyngitis (5%) and upper respiratory tract infection (4%); the incidence was similar in the placebo group (nasopharyngitis, 5% and upper respiratory tract infection, 3%).
• Through week 56, the most common AEs in TREMFYA-treated patients were infections (37.2 events per 100 PY); the number of events in the placebo group was 99.6 per 100 PY.
• The incidence of infections and serious infections reported as AEs and serious AEs through week 56 in the COSMOS study are reported in Table: Incidence of Infections through Week 56 in COSMOS.

• Serious infections were reported in 2 patients as follows:
  • A patient randomized to the TREMFYA group with a history of chronic obstructive pulmonary disease and heart disease was hospitalized with community-acquired pneumonia at week 12. Treatment with antibiotics led to recovery, and the patient resumed TREMFYA treatment.
  • A patient in the placebo→TREMFYA group was hospitalized with acute pneumonia at week 48. Treatment with antibiotics led to recovery, and the patient continued study participation.
• No OIs, cases of active TB, or deaths were reported.

Pooled Clinical Trial Data - Plaque pso and psA

Integrated Safety Analysis

Strober et al (2024)⁷ evaluated the safety of TREMFYA in an integrated pooled analysis of data from 11 randomized, phase 2 and 3 plaque PsO and PsA studies.

Study Design/Methods

• All plaque PsO studies (X-PLORE, VOYAGE 1, VOYAGE 2, ORION, Japan Registration) included a placebo-controlled period (weeks 0-16), except NAVIGATE (active comparator: ustekinumab) and ECLIPSE (active comparator: secukinumab).
• All active PsA studies (Phase 2, DISCOVER-1, DISCOVER-2, COSMOS) included a placebo-controlled period (weeks 0-24).
• This long-term safety analysis included a total of 4399 patients (PsO, n=2891; PsA, n=1508) who received ≥1 administration of TREMFYA for a total follow-up of 10,787 patient-years (PYs); see Table: Safety Reporting Period for Clinical Studies Included in the Integrated Analysis.
• The median duration of TREMFYA exposure was 1.7 years, 3.5 years, and 1.2 years in the pooled population, PsO group, and PsA group, respectively.

Results for Infections

• During the placebo-controlled period, the most common infections reported were nasopharyngitis and upper respiratory tract infection with EAIRs of 76.0/100 PY, and 72.2/100 PY in the TREMFYA and placebo groups, respectively.
• The EAIRs of infections per 100 PY of follow-up during the placebo-controlled period is presented in Table: Exposure Adjusted Incidence Rates of Infections Per 100 Patient-Years of Follow-Up (95% CI) During the Placebo-Controlled Period.

• The EAIR of infections in the TREMFYA group through the end of the reporting period was 61.2 per 100 PY.
• The EAIR of infections per 100 PY through the end of the reporting period are presented in Table: Pooled EAIRs of Infections through the End of the Reporting Period.

• The EAIR of serious infections was lower in the TREMFYA group (1 per 100 PY) compared to the placebo group (2.3 per 100 PY) during the placebo-controlled period and remained low with TREMFYA (1.0 per 100 PY) through the end of the reporting period.
• Through the end of reporting, following serious infections were reported in ≥1 patient in the TREMFYA group:
  • Pneumonia (n=15; 0.14/100 PY), cellulitis (n=12; 0.11/100 PY), appendicitis (n=10; 0.09/100 PY), diverticulitis (n=5; 0.05/100 PY), erysipelas (n=4; 0.04/100 PY), pyelonephritis (n=3; 0.03/100 PY), bronchitis (n=2; 0.02/100 PY), influenza (n=2; 0.02/100 PY), ovarian abscess (n=2; 0.02/100 PY), cystitis (n=2; 0.02/100 PY), urosepsis (n=2; 0.02/100 PY), and limb abscess (n=2; 0.02/100 PY).
• During the placebo-controlled period:
  • Three patients in the placebo group reported Candida infections (2 events of vulvovaginal candidiasis and 1 event of oral candidiasis; EAIR, 0.76/100 PY) and 2 patients in the TREMFYA group (1 event of vulvovaginal candidiasis and 1 event of cutaneous candidiasis; EAIR, 0.23/100 PY).
  • All the events of Candida infections occurred in PsO studies.
• Through the end of the reporting period:
  • Candida infections in the TREMFYA group remained low (EAIR, 0.50/100 PY) and included vulvovaginal candidiasis (n=23; 0.21/100 PY), cutaneous candidiasis (n=16; 0.15/100 PY), oral candidiasis (n=10; 0.09/100 PY), Candida infection (n=2; 0.02/100 PY), genital candidiasis (n=2; 0.02/100 PY), and Candida balanitis (n=1; 0.009/100 PY).
  • All events of Candida infections were reported in PsO studies, except for 1 case of oral thrush in DISCOVER-1 and 1 case of cutaneous candidiasis in DISCOVER-2 (EAIR of Candida infections in the pooled PsA studies through 2 years, 0.09/100 PY).
  • The rate of nonpathogen-specific fungal infections suspicious for Candida was low in the TREMFYA group (0.12/100 PY).
    • In the PsO and PsA population, the infections were as follows:
      • Vulvovaginal mycotic infection (n=9; 0.08/100 PY), oral fungal infection (n=2; 0.02/100 PY), fungal esophagitis (n=1; 0.009/100 PY), and genital fungal infection (n=1; 0.009/100 PY).
  • No OIs were reported in the TREMFYA group from PsO studies; however, 3 OIs were reported in the TREMFYA group (EAIR, 0.14/100 PY) from PsA studies.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 23 September 2024.

Summarized in this response are relevant data from phase 2 studies, phase 3 studies and pooled analyses of phase 2/3 studies.