FDA Approval Sought for 2 Pediatric Indications for Guselkumab

In July 2017, the U.S. Food & Drug administration (FDA) approved guselkumab (Tremfya) for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.¹ The FDA subsequently approved guselkumab for the treatment of adults with active psoriatic arthritis (PsA) and moderate to severe active ulcerative colitis. An injectable interleukin (IL) 23 antagonist, guselkumab is administered as a subcutaneous injection every four weeks for most of its current adult indications.² It is not currently approved for pediatric conditions. However, in December 2024, Johnson & Johnson submitted two supplemental biologics license applications (sBLAs) to the FDA for guselkumab for the treatment of:

• Children 5 years and older with active juvenile PsA; and
• Children 6 years and older with moderate to severe plaque psoriasis.³

Background: Juvenile PsA presents as chronic joint inflammation, with swelling and psoriasis. It’s a rare childhood condition affecting about 5% of patients with juvenile idiopathic arthritis (JIA). Children are classified by the International League of Associations for Rheumatology (ILAR) as having juvenile PsA if they have arthritis and psoriasis or if they don’t have psoriatic lesions but do have at least two of the following: dactylitis, nail pitting, onycholysis or a family history of psoriasis in a first-degree relative.⁴

Juvenile PsA differs from adult PsA. In juvenile PsA, skin disease often appears 10 years before the patient develops arthritis, which makes its diagnosis challenging.

Supporting Research

The application for guselkumab as a treatment for juvenile PsA is based on pharmacokinetic extrapolation analyses from two phase 3 PsA studies in adults, DISCOVER 1 (NCT03162796) and DISCOVER 2 (NCT03158285).^5,6 The application also includes efficacy and safety data from the PROTOSTAR (NCT03451851) study.⁷

DISCOVER 1 evaluated the efficacy and safety of subcutaneous guselkumab in participants with active PsA, including those previously treated with one to two tumor necrosis factor inhibitors (TNFi’s). The primary end point was achieving an ACR20 response at week 24. A total of 383 participants were enrolled, of whom 381 received at least one dose of guselkumab. In total, 126 patients received placebo, 127 patients received 100 mg of guselkumab at weeks 0 and 4, then once every eight weeks, and 128 patients received 100 mg of guselkumab once every four weeks.⁵

DISCOVER 2 evaluated the efficacy and safety of subcutaneous guselkumab in adult patients with active PsA who were biologic naive. The study’s primary end point was also the ACR20 response at week 24. A total of 741 participants were randomized into groups, and 739 participants received at least one dose of guselkumab. In the study groups, 246 patients received placebo, 248 patients received 100 mg of guselkumab at weeks 0 and 4, then once every eight weeks, and 245 patients received 100 mg of guselkumab once every four weeks.⁶

These two trials were used for the FDA approval of guselkumab for the treatment of PsA in adult patients. The pharmacokinetic data from these trials were extrapolated for the biologics license applications submission for juvenile PsA. More treatments are needed for younger patients and time will tell whether this agent garners approval for these patients.

Plaque Psoriasis

The phase 3 PROTOSTAR study evaluated the efficacy, safety and pharmacokinetics of subcutaneous guselkumab for the treatment of chronic plaque psoriasis in pediatric patients 6 years and older. The study’s primary end points were an Investigator Global Assessment score of 0/1 and Psoriasis Area and Severity Index 75 response at week 16. This study has been completed, but results have not yet been reported.

Michele B. Kaufman, PharmD, BCGP, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.

References

1. Tremfya (guselkumab) injection biologics license application approval letter. U.S. Food & Drug administration. 2017 Jul 13.
2. Highlights of prescribing information: Tremfya (guselkumab) injection. U.S. Food & Drug administration. 2024 Sep 11.
3. Johnson & Johnson seeks U.S. FDA approval for first pediatric indications for Tremfya (guselkumab) [news release]. Johnson & Johnson. 2024 Dec 2.
4. Brunello F, Tirelli F, Pegoraro L, et al. New insights on juvenile psoriatic arthritis. Front Pediatr. 2022 May 26:10:884727.
5. 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) [NCT03162796]. ClinicalTrials.gov. 2021 Feb 3.
6. A study evaluating the efficacy and safety of guselkumab administered subcutaneously in participants with active psoriatic arthritis [NCT03158285]. ClinicalTrials.gov. 2022 Dec 22.
7. A study to evaluate the efficacy, safety, and pharmacokinetics of subcutaneously administered guselkumab for the treatment of chronic plaque psoriasis in pediatric participants (PROTOSTAR) [NCT03451851]. ClinicalTrials.gov. 2025 Jan 13.