FDA Expands Approval of IL-23 Drug to Ulcerative Colitis

The FDA expanded the indications for guselkumab (Tremfya) to include adults with moderately to severely active ulcerative colitis, Johnson & Johnson announced on Wednesday.

Approval of the dual-acting interleukin (IL)-23 inhibitor in ulcerative colitis was based on findings from QUASAR, an ongoing phase IIb/III induction and maintenance program involving patients with inadequate response to conventional drugs, biologics, or a Janus kinase (JAK) inhibitor.

The studies showed that treatment with guselkumab led to higher rates of clinical remission at 44 weeks (45-50% vs 19% with placebo, P<0.001), which was the primary endpoint, and higher rates of endoscopic remission at 1 year of maintenance (34-35% vs 15%, P<0.001).

In the trials, some patients without a response at week 12 later achieved responses during maintenance.

“Treatment with Tremfya resulted in significant improvement in the chronic symptoms of ulcerative colitis, and importantly, normalization in the endoscopic appearance of the intestinal lining,” lead investigator David Rubin, MD, director of the Inflammatory Bowel Disease Center at University of Chicago Medicine, said in a statement. “Today’s approval of Tremfya builds on the clinical and well-established safety profile of this IL-23 inhibitor and marks a significant step forward in the treatment of this chronic inflammatory disease.”

IL-23 is a known driver of immune-mediated diseases like ulcerative colitis. Along with blocking IL-23, guselkumab also “binds to CD64, a receptor on cells that produce IL-23,” according to the drugmaker.

Guselkumab enters a crowded field of options for ulcerative colitis, however. Along with JAK inhibitors, tumor necrosis factor blockers, and the selective sphingosine-1-phosphate receptor modulator etrasimod (Velsipity), other agents that selectively block IL-23 have been approved by the FDA as well — including risankizumab (Skyrizi) and mirikizumab (Omvoh).

During induction, the recommended dosing for guselkumab is 200 mg intravenously at weeks 0, 4, and 8. Maintenance dosing options with subcutaneous injections include either a 100-mg dose every 8 weeks starting at week 16, or a 200-mg dose every 4 weeks starting at week 12. It is recommended to use the lowest effective dose that maintains treatment response.

Adverse events with the monoclonal antibody in the QUASAR program included respiratory tract infections (≥2%) during induction as well as injection site reactions, arthralgia, and upper respiratory tract infections (≥3%) during maintenance.

The drug’s labeling includes warnings and precautions about hypersensitivity reactions, including anaphylaxis; an increased risk for infections, with recommendations to evaluate for tuberculosis and other clinically important active infections prior to starting treatment; and a warning against the use of live vaccines.

Guselkumab is also approved for plaque psoriasis and active psoriatic arthritis and is being evaluated in Crohn’s disease.

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