Credit: luchschenF | stock.adobe.com
Pooled data from the Phase III GALAXI trial (NCT03466411) and the Phase III QUASAR maintenance trial (NCT04033445) show that Tremfya (guselkumab) produced high rates of endoscopic remission in both patients with Crohn disease (CD) and ulcerative colitis (UC), including among those who are biologic-naïve and biologic-refractory.1-3 Notably, these data, presented at the United European Gastroenterology Week 2024, demonstrated the superiority of Tremfya over Stelara (ustekinumab) among the overall CD patient population.1
“These results show the potential of Tremfya to offer a differentiated treatment option for patients with CD and UC, including those starting on a biologic for the first time, and those who have failed prior biologics and traditionally have been less likely to respond to other therapies,” Esi Lamousé-Smith, MD, PhD, vice president, Gastroenterology Disease Area Lead, Immunology, Johnson & Johnson Innovative Medicine, said in a press release.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 most recently for adult patients with moderately to severely active ulcerative colitis.4
The randomized, double-blind, placebo-controlled, active-controlled, multicenter GALAXI Phase II/III program analyzed the efficacy and safety of Tremfya in patients with moderately to severely active CD who showed an inadequate response or intolerance to conventional therapies and/or biologics. The program included the Phase II dose-ranging GALAXI 1 trial and the independent, identically designed, confirmatory Phase III GALAXI 2 and 3 trials. Each trial used a treat-through design, with patients remaining on the treatment that they were initially randomly assigned to, as well as a long-term extension trial tracking clinical, endoscopic, and safety outcomes with Tremfya for five years.
Among 873 patients in the GALAXI 2 and 3 dataset, 52% had previously shown an inadequate response to biologics, 41.8% were biologic-naïve, and 6% were biologic experienced without documented inadequate response or intolerance. The results of GALAXI 2 and 3 showed that Tremfya achieved superior rates of endoscopic remission compared to Stelara at week 48 in biologic-naïve patients with CD. Endoscopic remission was achieved by 44% of patients administered subcutaneous (SC) Tremfya 100 mg every eight weeks (q8w) and 46.1% of patients administered SC Tremfya 200 mg every four weeks (q4w), compared with 29.8% of patients administered Stelara.
The randomized, double-blind, placebo-controlled, parallel group, multicenter, Phase IIb/III QUASAR program analyzed the efficacy and safety of Tremfya in adult patients with moderately to severely active UC with a history of inadequate response or intolerance to conventional therapy, biologics, and/or JAK inhibitors. The QUASAR program included a Phase IIb dose-ranging induction trial, a confirmatory Phase III induction trial, and a Phase III, randomized withdrawal maintenance trial.
Patients enrolled in the induction trial were administered Tremfya 200 mg or placebo via intravenous infusion at weeks zero, four, and eight. For the maintenance trial, patients were administered an SC maintenance regimen of either Tremfya 100 mg every eight weeks, Tremfya 200 mg every four weeks, or placebo.
Among 568 patients enrolled in the QUASAR maintenance trial, 42.3% previously showed an inadequate response or intolerance to biologics or JAK inhibitors, 54.4% were biologic or JAK inhibitor naïve, and 3.3% were biologic or JAK inhibitor experienced without a documented history of inadequate response or intolerance. Investigators found that endoscopic remission was achieved by biologic and JAK inhibitor-refractory patients with UC, at rates of 31.2% in those administered Tremfya 100 mg q8w SC injection and 23.9% of those administered Tremfya 200 mg q4w SC injection, compared with 8% of those administered placebo.
Applications have been filed with regulatory authorities for Tremfya in the treatment of adults with moderately to severely active CD and for adults with moderately to severely active UC.
“Tremfya builds upon our nearly three decades of leadership in [inflammatory bowel disease] therapy and focused innovation in the IL-23 pathway to address the needs of people living with ulcerative colitis and delivering meaningful improvements in symptoms and the potential for sustained remission,” Lamousé-Smith said in the release.1
References
1. TREMFYA® (guselkumab) demonstrates impressive results across biologic-naïve and biologic-refractory patients in Crohn’s disease and ulcerative colitis. News release. Johnson & Johnson. October 10, 2024. Accessed October 11, 2024. https://www.jnj.com/media-center/press-releases/tremfya-guselkumab-demonstrates-impressive-results-across-biologic-naive-and-biologic-refractory-patients-in-crohns-disease-and-ulcerative-colitis.
2. A Study of the Efficacy and Safety of Guselkumab in Participants With Moderately to Severely Active Crohn’s Disease (GALAXI). ClinicalTrials.gov. Updated September 19, 2024. Accessed October 11, 2024. https://clinicaltrials.gov/study/NCT03466411
3. A Study of Guselkumab in Participants With Moderately to Severely Active Ulcerative Colitis (QUASAR). ClinicalTrials.gov. Updated September 19, 2024. Accessed October 11, 2024. https://clinicaltrials.gov/study/NCT04033445
4. 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 October 11, 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