Janssen Research & Development, LLC (Janssen) Phase 3 data presented for the first time at Digestive Disease Week® 2016 showed that a significantly greater proportion of adult patients with moderate to severe Crohn's disease receiving STELARA®(ustekinumab) subcutaneous (SC) maintenance therapy were in clinical remission at one year.
The Phase 3 IM-UNITI maintenance study, which evaluated 388 patients who achieved clinical response eight weeks after a single intravenous infusion of STELARA® in the UNITI-1 and UNITI-2 Phase 3 induction studies, showed that 53 percent of patients receiving a STELARA® 90 mg SC injection every eight weeks (Q8W) and 49 percent of patients receiving a STELARA® 90 mg SC injection every 12 weeks (Q12W) were in clinical remission at week 44, the study's primary endpoint, compared with 36 percent of patients receiving placebo (P = 0.005 and P = 0.040, respectively). Clinical remission was defined by a Crohn's Disease Activity Index (CDAI) score of less than 150 points; CDAI is a symptom-based disease assessment tool commonly used in clinical trials to quantify Crohn's disease activity.
Applications seeking approval of STELARA® for the treatment of moderately to severely active Crohn's disease are currently under review in the United States and Europe. STELARA®, approved for the treatment of moderate to severe plaque psoriasis and active psoriatic arthritis in many countries, is a novel biologic therapy that targets interleukin (IL)-12 and IL-23 cytokines, which are believed to play a role in immune-mediated diseases, including Crohn's disease.
"The totality of the induction and maintenance data over the course of one year show the potential of this biologic therapy in inducing and maintaining a clinically relevant therapeutic effect in patients with moderate to severe Crohn's disease," said William Sandborn, M.D., Chief, Division of Gastroenterology, and Professor of Medicine, University of California, San Diego, and study investigator. "The results of this comprehensive Phase 3 program-which included anti-tumor necrosis factor (TNF)-alpha naïve, exposed and failure patients-demonstrate the potential of STELARA® to provide significant benefit for patients in need of an effective therapy."
The IM-UNITI maintenance study represents the third pivotal study in the year-long, comprehensive Phase 3 clinical development program investigating STELARA® for the treatment of moderate to severe Crohn's disease. The findings, presented as part of the Distinguished Abstract Plenary at Digestive Disease Week 2016, follow Phase 3 results from the UNITI-1 induction study, which demonstrated the efficacy and safety of STELARA® in patients who had previously failed or were intolerant to treatment with one or more anti-TNF-alpha therapies, and the Phase 3 UNITI-2 induction study, which demonstrated the efficacy and safety of STELARA® in patients who had previously failed conventional therapy, the majority of whom were naïve to treatment with anti-TNF-alpha therapy. Patients responding to a single intravenous dose of STELARA® in the induction studies were re-randomized in the IM-UNITI maintenance study to receive STELARA® 90 mg SC Q8W, STELARA® 90 mg SC Q12W or placebo (withdrawal from therapy) and were followed for a combined one year of treatment. All patients randomized in the IM-UNITI maintenance study had achieved clinical response to STELARA® at week 8, and approximately 60 percent of patients were in clinical remission at entry into the IM-UNITI study.
Major secondary endpoints of the IM-UNITI study included clinical response, clinical remission among patients in remission after induction, corticosteroid-free remission, and clinical remission in patients refractory or intolerant to anti-TNF-alpha therapies (UNITI-1 subpopulation), all at week 44.
- Clinical response (an improvement in a CDAI score of at least 100 points after STELARA® induction) was maintained in a significantly greater proportion of patients receiving STELARA® 90 mg SC Q8W (59 percent) and STELARA® 90 mg SC Q12W (58 percent) compared with patients receiving placebo (44 percent) [P = 0.018 and P = 0.033, respectively].
- Of those patients who were in clinical remission at the start of the IM-UNITI study, 67 percent receiving STELARA® 90 mg SC Q8W and 56 percent of patients receiving STELARA® 90 mg SC Q12W were in clinical remission at week 44 compared with 46 percent of patients receiving placebo (P < 0.01; P = not significant, respectively).
- A significantly higher percentage of patients receiving STELARA® 90 mg SC Q8W (47 percent) and a higher percentage of patients receiving STELARA® 90 mg SC Q12W (43 percent) who were not receiving concomitant corticosteroids were in clinical remission at week 44 compared with 30 percent of patients receiving placebo (P = 0.004; nominal P = 0.035, respectively).
- Numerically higher proportions within the subgroup of patients who had previously failed or were intolerant to treatment with one or more anti-TNF-alpha therapies (UNITI-1 subpopulation) achieved clinical remission while receiving STELARA® maintenance therapy at week 44, with similar treatment effects to the overall population, (41 percent for STELARA® 90 mg SC Q8W and 39 percent for STELARA® 90 mg SC Q12W) compared with 26 percent of patients receiving placebo (P = not significant for both).
Through week 44 (placebo-controlled period), adverse events (AEs) were reported in similar proportions across STELARA® and placebo treatment groups. Serious AEs occurred in 10 percent, 12 percent and 15 percent of patients receiving a STELARA® 90 mg SC Q8W, STELARA® 90 mg SC Q12W and placebo, respectively; 2 percent, 5 percent and 2 percent of patients reported serious infections in these respective groups. In the placebo controlled period, no deaths or major adverse cardiovascular events (MACE) were reported, and two patients reported malignancies (one case of basal cell carcinoma in each of the placebo and STELARA® 90 mg SC Q8W groups).
"These maintenance data complement the induction data previously presented and provide important insights into the efficacy and safety profile of STELARA® for the treatment of moderately to severely active Crohn's disease," said Newman Yeilding, M.D., Head of Immunology Development, Janssen Research & Development, LLC. "Pending approval, we look forward to bringing STELARA® to patients who may benefit from this new therapeutic option and providing gastroenterologists with a new alternative to treat Crohn's disease."
Additional data from the STELARA® Phase 3 Crohn's disease clinical development program being presented at Digestive Disease Week®2016 include:
- Assessment of Serum C-Reactive Protein, Fecal Lactoferrin, and Fecal Calprotectin in Patients With Moderate-Severely Active Crohn's Disease: Results From the IM-UNITI Maintenance Study
- Evidence of Content Validity and Psychometric Properties of SF-36 for Measuring Health-Related Quality of Life of Patients With Crohn's Disease
- Molecular Response to Ustekinumab in Moderate-to-severe Crohn's Disease by Serum Protein Analysis: Results from UNITI-1 Induction, UNITI-2 Induction, and IM-UNITI Maintenance Studies
- Pharmacokinetics and Exposure-Response Relationships of Ustekinumab during IV Induction and SC Maintenance Treatment of Patients with Crohn's Disease with Ustekinumab: Results from the UNITI-1, UNITI-2, and IM-UNITI Studies
- Ustekinumab Improves General Health Status and Disease-Specific Health Related Quality of Life of Patients with Moderate to Severe Crohn's Disease: Results from the UNITI and IM-UNITI Phase 3 Clinical Trials
About the IM-UNITI Trial
IM-UNITI, a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel group study, evaluated the efficacy and safety of STELARA® maintenance therapy in adult patients with moderate to severe Crohn's disease. Patients (n=388) who had responded to a single intravenous dose of STELARA® in the UNITI-1 or UNITI-2 induction studies were randomized equally to receive maintenance SC injections of STELARA® 90 mg SC Q8W or Q12W, or placebo). Together, the UNITI-1 and UNITI-2 induction studies and the IM-UNITI maintenance study represent one year of therapy. The primary endpoint was clinical remission at week 44, defined by CDAI scores less than 150 points. Major secondary endpoints at week 44 included clinical response, measured by the proportion of patients who achieved at least a 100-point reduction from baseline CDAI scores, corticosteroid-free clinical remission, clinical remission among patients in remission at the start of the IM-UNITI study, and clinical remission in the subgroup of patients refractory or intolerant to treatment with one or more anti-TNF-alpha therapies.
About Crohn's Disease
More than five million people worldwide are living with Crohn's disease and ulcerative colitis-collectively known as inflammatory bowel disease (IBD).1 Crohn's disease is a chronic inflammatory condition of the gastrointestinal tract that affects approximately 700,000 Americans. The cause of Crohn's disease is not known, but the disease is associated with abnormalities of the immune system that could be triggered by a genetic predisposition or diet and other environmental factors. Symptoms of Crohn's disease can vary but often include abdominal pain and tenderness, frequent diarrhea, rectal bleeding, weight loss and fever. There is currently no cure for Crohn's disease.2
About STELARA® (ustekinumab)
STELARA®, a human IL-12 and IL-23 antagonist, is approved in the United States for the treatment of adult patients (18 years or older) with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. STELARA® is also approved for the treatment of adult patients (18 years or older) with active psoriatic arthritis and can be used alone or in combination with methotrexate (MTX).
The Janssen Pharmaceutical Companies of Johnson & Johnson maintain exclusive worldwide marketing rights to STELARA®, which is currently approved for the treatment of moderate to severe plaque psoriasis in 87 countries and psoriatic arthritis in 71 countries.
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1. World IBD Day. Home. Available at http://www.worldibdday.org/index.html. Accessed May 10, 2016
2. Crohn's & Colitis Foundation of America. What is Crohn's Disease?. Available at http://www.ccfa.org/what-are-crohns-and-colitis/what-is-crohns-disease/. Accessed May 10, 2016.