New Phase 3 study findings show Stelara maintained clinical remission after one year of treatment in patients with moderate to severe Crohn's disease

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 ustekinumab in the UNITI-1 and UNITI-2 Phase 3 induction studies, showed that 53 percent of patients receiving a ustekinumab 90 mg SC injection every eight weeks (Q8W) and 49 percent of patients receiving a ustekinumab 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).¹ 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.¹

Applications seeking approval of ustekinumab for the treatment of moderately to severely active Crohn's disease are currently under review in the United States and Europe. Ustekinumab, 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.²

"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 programme - which included anti-tumor necrosis factor (TNF)-alpha naïve, exposed and failure patients - demonstrate the potential of ustekinumab 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 programme investigating ustekinumab 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 ustekinumab in patients who had previously failed or were intolerant to treatment with one or more anti-TNF-alpha therapies (anti-TNF failure population),³ and the Phase 3 UNITI-2 induction study, which demonstrated the efficacy and safety of ustekinumab in patients who had previously failed conventional therapy, the majority of whom were naïve to treatment with anti-TNF-alpha therapy.4 Patients responding to a single intravenous dose of ustekinumab in the induction studies were re-randomised in the IM- UNITI maintenance study to receive ustekinumab 90 mg SC Q8W, ustekinumab 90 mg SC Q12W or placebo (withdrawal from therapy) and were followed for a combined one year of treatment.¹ All patients randomised in the IM-UNITI maintenance study had achieved clinical response to ustekinumab at week 8,¹ and approximately 60 percent of patients were in clinical remission at entry into the IM-UNITI study.⁴

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 44.¹

• Clinical response (an improvement in a CDAI score of at least 100 points after ustekinumab induction) was maintained in a significantly greater proportion of patients receiving ustekinumab 90 mg SC Q8W (59 percent) and ustekinumab 90 mg SC Q12W (58 percent) compared with patients receiving placebo (44 percent) (P = 0.018 and P = 0.033, respectively)¹
• Of those patients who were in clinical remission at the start of the IM-UNITI study, 67 percent receiving ustekinumab 90 mg SC Q8W and 56 percent of patients receiving ustekinumab 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)¹
• A significantly higher percentage of patients receiving ustekinumab 90 mg SC Q8W (47 percent) and a higher percentage of patients receiving ustekinumab 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)¹
• 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 ustekinumab maintenance therapy at week 44, with similar treatment effects to the overall population, (41 percent for ustekinumab 90 mg SC Q8W and 39 percent for ustekinumab 90 mg SC Q12W) compared with 26 percent of patients receiving placebo (P = not significant for both)¹

Through week 44 (placebo-controlled period), adverse events (AEs) were reported in similar proportions across ustekinumab and placebo treatment groups. Serious AEs occurred in 10 percent, 12 percent and 15 percent of patients receiving a ustekinumab 90 mg SC Q8W, ustekinumab 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 ustekinumab 90 mg SC Q8W groups).¹

"These maintenance data complement the induction data previously presented and provide important insights into the efficacy and safety profile of ustekinumab 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 ustekinumab to patients who may benefit from this new therapeutic option and providing gastroenterologists with a new alternative to treat Crohn's disease."

About the IM-UNITI Trial¹

IM-UNITI, a Phase 3, multicentre, randomised, double-blind, placebo-controlled, parallel group study, evaluated the efficacy and safety of ustekinumab maintenance therapy in adult patients with moderate to severe Crohn's disease. Patients (n=388) who had responded to a single intravenous dose of ustekinumab in the UNITI-1 or UNITI-2 induction studies were randomised equally to receive maintenance SC injections of ustekinumab 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.