The FINANCIAL — Phase 3 data presented for the first time showed treatment with STELARA (ustekinumab) induced clinical response and clinical remission in patients with moderate to severe Crohn’s disease who had previously failed conventional therapy, the majority of whom were naïve to treatment with anti-tumor necrosis factor (TNF)-alpha therapy.
The Phase 3 Janssen Research & Development, LLC-sponsored UNITI-2 study achieved its primary endpoint with STELARA treatment groups demonstrating significantly higher rates of clinical response at week 6 when compared with the placebo group. Major secondary endpoints of clinical response and clinical remission at week 8 were also significantly higher among patients receiving STELARA compared with patients receiving placebo. STELARA, approved for the treatment of moderate to severe plaque psoriasis and active psoriatic arthritis in many countries, is a monoclonal antibody that targets interleukin (IL)-12 and IL-23 cytokines believed to play a role in immune-mediated diseases, including Crohn’s disease, according to Johnson & Johnson.
“The UNITI-2 study results show STELARA induced clinical response and remission in patients with moderate to severe Crohn’s disease who had failed steroids and/or immunosuppressive therapy, but had not failed TNF inhibitors,” said Brian Feagan, M.D., Professor of Medicine, Chief Executive Officer and Senior Medical Director, Robarts Research Institute, University of Western Ontario, and study investigator. “Findings from this Phase 3 program provide an important first look into the efficacy and safety of STELARA induction therapy in the treatment of inflammatory bowel disease—a disease where new therapeutic options are needed as the incidence continues to rise globally.”
Patients participating in the Phase 3 UNITI-2 study received a single intravenous (I.V.) infusion of placebo, STELARA 130 mg or STELARA ~6 mg/kg (weight-tiered dosing: patients weighing less than or equal to 55 kg received 260 mg; patients weighing more than 55 kg and less than or equal to 85 kg received 390 mg; and patients weighing more than 85 kg received 520 mg) at week 0. Enrolled patients had previously failed steroids and/or immunomodulators and were either naïve to or had been exposed to anti-TNF-alpha therapy, but had not failed such biologic therapy.
At week 6, 52 percent of patients receiving STELARA 130 mg and 56 percent of patients receiving STELARA ~6 mg/kg achieved clinical response, as defined by a reduction from baseline in the Crohn’s Disease Activity Index (CDAI) score of at least 100 points, compared with 29 percent of patients receiving placebo (P < 0.001). CDAI is a symptom-based disease assessment tool commonly used in clinical trials to quantify Crohn’s disease activity.
At week 8, 47 percent and 58 percent of patients receiving STELARA 130 mg and STELARA ~6 mg/kg, respectively, achieved clinical response, compared with 32 percent of patients receiving placebo (P < 0.001). In addition, 31 percent of patients receiving STELARA 130 mg and 40 percent of patients receiving STELARA ~6 mg/kg achieved clinical remission at week 8, as defined by a CDAI score of less than 150 points, compared with 20 percent of patients receiving placebo (P = 0.009 for STELARA 130 mg; P < 0.001 for STELARA ~6 mg/kg).
In addition to significant improvements in signs and symptoms as measured by CDAI, both doses of STELARA resulted in statistically significant improvements in the Inflammatory Bowel Disease Questionnaire (IBDQ), a health-related quality of life measure for patients with IBD, as well as markers of inflammation, including C-reactive protein (CRP), fecal lactoferrin and calprotectin.
Through week 8, adverse events (AEs), serious AEs and infections (including serious infections) were reported in similar proportions across STELARA and placebo treatment groups. No malignancies, deaths, opportunistic infections, cases of tuberculosis or major adverse cardiovascular events (MACE) were observed in patients treated with STELARA.
“The STELARA Phase 3 UNITI-2 induction results are important findings, as induction of clinical response and clinical remission are important goals in the management of Crohn’s disease,” said Newman Yeilding, M.D., Head of Immunology Development, Janssen Research & Development, LLC. “We look forward to filing applications this year seeking approval of STELARA for the treatment of moderate to severe Crohn’s disease and remain committed to the continued development of this innovative medicine for the treatment of immune-mediated diseases.”