Two supplemental biologics license applications (sBLAs) for guselkumab (Tremfya; Johnson & Johnson) seeking approval for pediatric indications were submitted to the FDA. The new indications would be for the treatment of children aged 6 years and older with moderate to severe plaque psoriasis (PsO) and children aged 5 years and older with active juvenile psoriatic arthritis (jPsA).1
Guselkumab is the first approved monoclonal antibody that selectively binds to the p19 subunit of interleukin (IL)-23—an important driver of immune-mediated diseases such as plaque PsO and PsA—and inhibits its interaction with the IL-23 receptor. It originally received FDA approval in July 2017 for moderate-to-severe plague PsO and July 2020 for PsA. Additionally, guselkumab received FDA approval for the treatment of moderate to severe ulcerative colitis in September 2024.1,2
According to experts, the PsO sBLA submission follows data from the phase 3 PROTOSTAR study (NCT03451851)3, which enrolled pediatric patients with moderate-to-severe plague PsO to bridge pharmacokinetic data from the phase 3 VOYAGE 1 (NCT02207231) and 2 (NCT02207244) studies that evaluated adult patients. The jPsA submission was based on pharmacokinetic extrapolation analyses from the adult PsA studies DISCOVER-1 (NCT03162796)4 and DISCOVER-2 (NCT03158285)5 as well as guselkumab efficacy and safety data demonstrated in the PROTOSTAR study.1
About the Trials
PROTOSTAR
- Trial Name: A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Subcutaneously Administered Guselkumab for the Treatment of Chronic Plaque Psoriasis in Pediatric Participants (PROTOSTAR)
- ClinicalTrials.gov ID: NCT03451851
- Sponsor: Janssen Research & Development, LLC
- Completion Date (Estimated): December 18, 2026
DISCOVER-1
- Trial Name: A Study Evaluating the Efficacy and Safety of Guselkumab Administered Subcutaneously in Participants With Active Psoriatic Arthritis Including Those Previously Treated With Biologic Anti -Tumor Necrosis Factor (TNF) Alpha Agent(s) (Discover-1)
- ClinicalTrials.gov ID: NCT03162796
- Sponsor: Janssen Research & Development, LLC
- Completion Date: November 18, 2019
DISCOVER-2
- Trial Name: A Study Evaluating the Efficacy and Safety of Guselkumab Administered Subcutaneously in Participants With Active Psoriatic Arthritis
- ClinicalTrials.gov ID: NCT03158285
- Sponsor: Janssen Research & Development, LLC
- Completion Date: November 10, 2020
The PROTOSTAR study (NCT03451851) is a randomized, multicenter, placebo- and active comparator-controlled phase 3 trial evaluating the efficacy, safety, and pharmacokinetics of guselkumab when subcutaneously administered in pediatric patients with plague PsO aged 6 to 17 years. Patients received doses of guselkumab or placebo based on their weight, and the active comparator doses of etanercept (Enbrel; Immunex Corp) was also weight-based, but the maximum dose was 50 mg. Co-primary end points were Investigator’s Global Assessment (IGS) score of 0 or 1 and percentage of patients who achieve a Psoriasis Area and Severity Index (PASI) 75 response at week 16. The trial is currently ongoing.1,3
DISCOVER-1 (NCT03162796) and DISCOVER-2 (NCT03158285) were both multicenter, randomized, double-blind studies that evaluated the efficacy and safety of 100 mg of subcutaneously administered guselkumab compared with placebo in patients with active PsA. DISCOVER-1 included patients previously treated with 1 to 2 tumor necrosis factor inhibitors (TNFi), whereas DISCOVER-2 included biologic-naïve patients. The primary end point for both studies was percentage of patients who achieved an American College of Rheumatology 20 response at week 24.1,4,5
The findings for DISCOVER-1 and DISCOVER-2 demonstrated that through week 24, adverse events (AEs) were consistent between patients who were treated with placebo and guselkumab. The investigators observed that AEs were about 142.8 per 100 people-years and 150.6 per 100 people-years, whereas serious AEs were 7.1 per 100 people-years and 4.4 per 100 people-years, respectively. In addition, AEs that lead to discontinuation of treatment were about were 4.1 per 100 people-years and 3.8 per 100 people-years, respectively.6
Further, patients treated with guselkumab had no occurrences of uveitis, active tuberculosis, opportunistic infections, or inflammatory bowel disease, and low rates of malignancy and major adverse cardiovascular events through 1 year. Additionally, injection site reactions were reported by approximately 1.7% of patients, and antibodies to guselkumab in 4.5% of patients through 1 year. Most antibodies to guselkumab were nonneutralizing. Serum hepatic transaminase elevations and decreased neutrophil counts were also observed, but these were generally mild, transient, and did not require treatment discontinuation, with minimal change from week 24 to 1 year.6
"There is a critical gap in the treatment of children and adolescents with these skin and joint conditions, where debilitating symptoms can present challenges related to physical appearance and ability to function…we are working to address this gap by investigating the efficacy and well-characterized safety profile of [guselkumab] for pediatric patients,” Liza O'Dowd, MD, vice president, immunodermatology disease area leader, Johnson & Johnson Innovative Medicine, said in a news release.1
REFERENCES
PR Newswire. Johnson & Johnson seeks U.S. FDA approval for first pediatric indications for TREMFYA® (guselkumab). News release. December 2, 2024. Accessed December 3, 2024. https://www.prnewswire.com/news-releases/johnson--johnson-seeks-us-fda-approval-for-first-pediatric-indications-for-tremfya-guselkumab-302317847.html
Gallagher, A. FDA Approves Guselkumab for Treatment of Ulcerative Colitis. Pharmacy Times. September 12, 2024. Accessed December 3, 2024. https://www.pharmacytimes.com/view/fda-approves-guselkumab-for-treatment-of-ulcerative-colitis
A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Subcutaneously Administered Guselkumab for the Treatment of Chronic Plaque Psoriasis in Pediatric Participants (PROTOSTAR). ClinicalTrials.gov identifier: NCT03451851. Updated October 15, 2024. Accessed December 3, 2024. https://clinicaltrials.gov/study/NCT03451851
A Study Evaluating the Efficacy and Safety of Guselkumab Administered Subcutaneously in Participants With Active Psoriatic Arthritis Including Those Previously Treated With Biologic Anti -Tumor Necrosis Factor (TNF) Alpha Agent(s) (Discover-1). ClinicalTrials.gov identifier: NCT03162796. Updated February 3, 2021. Accessed December 3, 2024. https://clinicaltrials.gov/study/NCT03162796
A Study Evaluating the Efficacy and Safety of Guselkumab Administered Subcutaneously in Participants With Active Psoriatic Arthritis. ClinicalTrials.gov identifier: NCT03158285. Updated December 22, 2022. Accessed December 3, 2024. https://clinicaltrials.gov/study/NCT03158285
Rahman P, Ritchlin CT, Helliwell PS, et al. Pooled Safety Results Through 1 Year of 2 Phase III Trials of Guselkumab in Patients With Psoriatic Arthritis. J Rheumatol. 2021;48 (12)1815-1823; doi:10.3899/jrheum.201532
