Interim Results Released from Phase 2 Study on TREMFYA®▼ (guselkumab) in Patients with Crohn’s Disease

Oct 14, 2020

The Janssen Pharmaceutical Companies of Johnson & Johnson have released Phase 2 interim data from the GALAXI 1 study, which showed TREMFYA® (guselkumab) demonstrated results at week 12 in adult patients with moderately to severely active Crohn’s disease (CD) with inadequate response or intolerance to conventional therapies and/or biologics.

CD is one of the two main forms of inflammatory bowel disease, which affects up to 2 million people across Europe. CD is a chronic inflammatory condition of the gastrointestinal tract with no known cause, but the disease is associated with abnormalities of the immune system that could be triggered by a genetic predisposition, diet or other environmental factors. Symptoms of CD can vary but often include abdominal pain and tenderness, frequent diarrhoea, rectal bleeding, weight loss and fever.

Guselkumab is the first approved fully human monoclonal antibody that selectively binds to the p19 subunit of interleukin (IL)-23 and inhibits its interaction with the IL-23 receptor. Guselkumab is approved in the EU, U.S., Canada, Japan and a number of other countries worldwide for the treatment of adult patients with moderate to severe plaque psoriasis who may benefit from taking injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet [UV] light). IL-23 is an important driver of the pathogenesis of immune-mediated inflammatory diseases such as psoriasis.

At 12 weeks, guselkumab induced significantly greater improvements compared to placebo across key clinical and endoscopic outcome measures, with a safety profile consistent with approved indications. Guselkumab is not currently approved for the treatment of CD in the European Union (EU).

These new data were presented as an oral presentation (Abstract OP089) at the 28th United European Gastroenterology (UEG) Week.

“While there have been substantial treatment breakthroughs in Crohn’s disease, there are still patients who are not gaining benefit from any of the currently approved mechanisms of action for their symptoms,” said lead study investigator William J. Sandborn, M.D., Chief of Gastroenterology, Professor of Medicine, University of California, San Diego, who is delivering the oral presentation virtually at UEG Week. “I am encouraged by these early data, which show that guselkumab across three different dosing groups induced a significant response in key clinical and endoscopic outcome measures in Crohn’s disease.”

GALAXI 1 evaluated the efficacy and safety of guselkumab compared with placebo in CD. The interim analyses reported results through week 12 from the first 250 patients enrolled. Approximately 50 percent of patients had previously failed biologic therapy; and baseline disease characteristics were consistent with moderately to severely active CD (Crohn’s Disease Activity Index [CDAI], mean 306.6; Simple Endoscopic Score for Crohn’s Disease [SES-CD], median 11.0). Patients were randomised equally into five treatment arms, including treatment with guselkumab dosed at 200, 600 or 1200 mg intravenously (IV) at weeks 0, 4 and 8, respectively; or treatment with ustekinumab dosed at ~6 mg/kg IV at week 0 and then dosed at 90 mg subcutaneously at week 8; or placebo.

At week 12, there were significantly greater reductions from baseline in the CDAI observed in each guselkumab group (200, 600 or 1200 mg IV doses) compared with placebo (Least Squares [LS] means: -154.1, -144.3 and -149.5 versus -36.0, respectively; all p<0.001). A significantly higher proportion of patients assigned to each guselkumab dose achieved clinical remission compared with placebo (CDAI<150): 54.0 percent, 56.0 percent, 50.0 percent, respectively, versus 15.7 percent (p<0.001). Among conventional therapy failures, 61.6 percent in the guselkumab-combined group versus 18.5 percent treated with placebo achieved clinical remission at week 12. Among patients who had previously failed biologic therapy, 45.5 percent in the guselkumab combined group compared with 12.5 percent in the placebo group achieved clinical remission at week 12.1 Furthermore, at week 12, a significantly higher proportion of patients treated with guselkumab achieved clinical response (p<0.001), patient reported outcome (PRO)-2 remission (p<0.001), clinical-biomarker response (p<0.001), and endoscopic response (p<0.001) compared with patients treated with placebo. Endoscopic healing is an important outcome for long-term disease control; 37.3 percent of patients in the guselkumab-combined group compared with 11.8 percent in the placebo group achieved endoscopic response after only 12 weeks of induction treatment (p<0.001).1

“For patients living with moderately to severely active Crohn’s disease, including those who have not had an adequate response or have intolerance to other therapies, these results show that guselkumab may play an important role as a new treatment option pending results from the ongoing registration trials,” said Jan Wehkamp, M.D., Vice President, Gastroenterology Disease Area Leader, Janssen Research & Development, LLC. “Although more research is needed, we are encouraged by the data and the potential role for selective IL-23 inhibition in helping patients manage their Crohn’s disease symptoms and treating the underlying disease process.”