J&J Seeks FDA Approval for Subcutaneous Guselkumab Induction in Ulcerative Colitis
核心洞察
Johnson & Johnson submitted a sBLA to the FDA for a subcutaneous induction regimen of guselkumab (Tremfya) to treat adults with moderately to severely active ulcerative colitis (搜索).
The submission is based on Phase 3 ASTRO study data, which showed statistically significant and clinically meaningful results for clinical remission at week 12.
Guselkumab is a fully human, dual-acting monoclonal antibody that neutralizes inflammation by blocking IL-23 (搜索) and binding to CD64 (搜索).
Johnson & Johnson has submitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) seeking approval for a subcutaneous (SC) induction regimen of guselkumab (Tremfya) for the treatment of adults with moderately to severely active ulcerative colitis (搜索) (UC). This submission is supported by data from the phase 3 ASTRO study, which evaluated the efficacy and safety of guselkumab SC induction therapy in this patient population.
The sBLA aims to expand the approved uses of guselkumab, already available for UC via intravenous induction followed by subcutaneous maintenance. The potential approval of a fully SC induction and maintenance regimen would provide versatility and convenience for both patients and healthcare providers in managing inflammatory bowel disease (IBD).
ASTRO Study Details and Results
The phase 3 ASTRO study was a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. It assessed guselkumab SC induction therapy (400 mg at weeks 0, 4, and 8) in adults with moderately to severely active UC who had an inadequate response or intolerance to conventional therapy, prior biologics, and/or ozanimod or approved JAK inhibitors. Patients were randomized (1:1:1) to receive:
- Guselukmab 400 mg SC induction at weeks 0, 4, and 8 followed by guselkumab 200 mg SC every 4 weeks
- Guselkumab 400 mg SC induction at weeks 0, 4 and 8, followed by guselkumab 100 mg SC every 8 weeks
The study met its primary endpoint, demonstrating statistically significant and clinically meaningful results for clinical remission at week 12 with the 400 mg SC induction dose of guselkumab administered at weeks 0, 4, and 8. All secondary endpoints, including endoscopic improvement and histologic-endoscopic mucosal improvement, were also met. The safety data from ASTRO were consistent with the safety findings from the QUASAR program.
Guselkumab Mechanism of Action
Guselkumab is the first approved fully human, dual-acting monoclonal antibody designed to neutralize inflammation at its source. It functions by blocking interleukin (IL)-23 and binding to CD64 (搜索), a receptor on the cell that produces IL-23 (搜索). This mechanism helps to reduce the inflammatory response in patients with UC.
Current Guselkumab Approvals and Usage
Guselkumab received FDA approval for UC on September 11, 2024, based on data from the phase 2b/3 QUASAR study. This study highlighted guselkumab’s ability to induce clinical and endoscopic remission in adult patients with moderately to severely active UC who had an inadequate response or intolerance to conventional therapy, other biologics, and/or JAK inhibitors. In addition to UC, guselkumab is also approved for treating adults with moderate to severe plaque psoriasis (搜索) and active psoriatic arthritis (搜索).
Currently, the approved regimen for UC involves a 200 mg intravenous induction dose at weeks 0, 4, and 8, followed by a maintenance dosage of either 100 mg SC every 8 weeks or 200 mg SC every 4 weeks.