Johnson & Johnson Seeks FDA Approval for Subcutaneous Tremfya Regimen for Ulcerative Colitis

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Johnson & Johnson has submitted a supplemental Biologics License Application (sBLA) to the FDA seeking the approval of a subcutaneous (SC) induction regimen of Tremfya (guselkumab) to treat adult patients with moderately to severely active ulcerative colitis (UC).¹ The sBLA submission is based on positive findings from the Phase III ASTRO trial (NCT05528510),² which demonstrated significant clinical remission and safety consistency with Tremfya in this patient population.

"With the ASTRO study in UC and the GRAVITI study in Crohn's disease, we are focused on delivering versatility and options for administration of treatment for people with inflammatory bowel disease (IBD),” Esi Lamousé-Smith, MD, PhD, vice president, Gastroenterology Disease Area lead, Immunology, Johnson & Johnson Innovative Medicine, said in a press release. “Tremfya is the first IL-23 inhibitor to potentially offer a fully SC induction and maintenance regimen, which if approved, can provide choice and simplicity for patients and providers."¹

Tremfya was the first FDA-approved, fully-human, dual-acting monoclonal antibody to block interleukin (IL)-23—a significant driver of the pathogenesis of inflammatory diseases—by attaching to the p19 subunit of IL-23 and to CD64, a receptor on cells that produce IL-23. Tremfya is currently indicated to treat adult patients with moderate to severe plaque psoriasis who may benefit from systemic therapy or phototherapy; for adult patients with active psoriatic arthritis; and was most recently approved in September 2024 for adults with moderately to severely active UC.³

The FDA granted the approval of Tremfya for UC based on findings from the ongoing randomized, double-blind, placebo-controlled, parallel group, multicenter Phase II/III QUASAR trial (NCT04033445), which analyzed its efficacy and safety in UC patients who showed an inadequate response or intolerance to conventional therapy, prior biologics, and/or Janus kinase (JAK) inhibitors. Results of the QUASAR trial show that patients administered Tremfya achieved significant clinical and endoscopic improvements, as 50% of patients administered the 200 mg dose and 45% administered the 100 mg dose experienced clinical remission by week 44, compared to 19% of patients administered placebo.³

The randomized, double-blind, placebo-controlled, parallel-group, multicenter, treat-through ASTRO trial analyzed the efficacy and safety of Tremfya as SC induction therapy at a dose of 400 mg administered at weeks zero, four, and eight. The trial included adults with moderately to severely active UC who showed an inadequate response or intolerance to conventional therapy, prior biologics therapy, and/or ozanimod or approved JAK inhibitors.

Patients were randomly assigned in a 1:1:1 ratio to receive Tremfya 400 mg SC induction at weeks zero, four, and eight followed by Tremfya 200 mg SC every four weeks (q4w); or Tremfya 400 mg SC induction at weeks zero, four, and eight, followed by Tremfya 100 mg SC every eight weeks (q8w); or placebo. Maintenance doses of Tremfya in the ASTRO trial of 200 mg SC q4w and 100 mg SC q8w were the same dosages as those evaluated in the Phase III QUASAR program, which established the efficacy and safety of intravenous induction followed by SC maintenance therapy in patients with moderately to severely active UC.

Tremfya achieved the primary endpoint of the ASTRO trial by producing statistically significant and clinically meaningful clinical remission at week 12 with the 400 mg SC induction dose administered at weeks zero, four, and eight. Tremfya also achieved the trial’s secondary endpoints, which included endoscopic improvement and histologic-endoscopic mucosal improvement. In terms of safety, adverse event (AE) reports were consistent with prior findings from the QUASAR program. The most common AEs associated with Tremfya include respiratory tract infections, injection site reactions, and arthralgia.

Full results from the ASTRO trial are planned to be presented at upcoming medical meetings, according to Johnson & Johnson.

“The ASTRO results add to the compelling data generated from the QUASAR program in UC and build on the promise of Tremfya in the treatment of IBD as we look to transform outcomes for patients,” Lamousé-Smith added.¹

References

1. Johnson & Johnson seeks U.S. FDA approval for subcutaneous induction regimen of TREMFYA® (guselkumab) in ulcerative colitis, a first for an IL-23 inhibitor. News release. Johnson & Johnson. November 22, 2024. Accessed November 22, 2024. https://prnmedia.prnewswire.com/news-releases/johnson--johnson-seeks-us-fda-approval-for-subcutaneous-induction-regimen-of-tremfya-guselkumab-in-ulcerative-colitis-a-first-for-an-il-23-inhibitor-302313913.html

2. A Study of Guselkumab Therapy in Participants With Moderately to Severely Active Ulcerative Colitis (ASTRO). ClinicalTrials.gov. Updated October 31, 2024. Accessed November 22, 2024. https://clinicaltrials.gov/study/NCT05528510?term=astro&intr=guselkumab&rank=1

3. TREMFYA® (guselkumab) receives U.S. FDA approval for adults with moderately to severely active ulcerative colitis, strengthening Johnson & Johnson’s leadership in inflammatory bowel disease. J&J. September 11, 2024. Accessed November 22, 2024. https://www.jnj.com/media-center/press-releases/tremfya-guselkumab-receives-u-s-fda-approval-for-adults-with-moderately-to-severely-active-ulcerative-colitis-strengthening-johnson-johnsons-leadership-in-inflammatory-bowel-disease