BMS Presents Positive Late-Breaking Data from Phase 3 True North Trial Evaluating Zeposia in Adult Patients with Moderate to Severe Ulcerative Colitis
Posted on October 13, 2020
Bristol Myers Squibb announced detailed results from True North, a pivotal, placebo-controlled Phase 3 trial evaluating oral Zeposia (ozanimod) as an induction and maintenance therapy in adult patients with moderate to severe ulcerative colitis (UC). True North met both primary endpoints, demonstrating highly statistically significant and clinically meaningful results for clinical remission compared to placebo at induction at Week 10 (18.4% versus 6.0%; p-value<0.0001) and in maintenance at Week 52 (37.0% vs 18.5%; p<0.0001).The study also met key secondary endpoints, including clinical response, endoscopic improvement and mucosal healing in induction at Week 10 and in maintenance at Week 52. Significantly more patients treated with Zeposia compared to placebo achieved clinical response at Week 10 (47.8% vs 25.9%; p<0.0001) and at Week 52 (60.0% vs 41.0%; p<0.0001) with consistent results across sub-analyses. The overall safety observed was consistent with the known safety profile for Zeposia and patients with moderate to severe UC.
Efficacy and safety results from the 10-week induction period (Abstract LB02, UEG Research Prize 2020 Session) and from the maintenance period at Week 52 (Abstract LB10) from True North will be presented on October 11 at 12:32 CEST and at 15:24 CEST, respectively, in two late-breaking oral presentations at UEG Week Virtual 2020.
“The data from the Zeposia True North trial demonstrate patients with moderate to severe ulcerative colitis achieved clinically meaningful improvements in key clinical, endoscopic and mucosal healing endpoints,” said William Sandborn, M.D., chief, Division of Gastroenterology and director, Inflammatory Bowel Disease Center at University of California (UC), San Diego Health and professor of medicine, UC San Diego School of Medicine. “Notably, the endoscopic and histologic benefits, which can be difficult to achieve, suggest Zeposia has the potential to address the need for a safe and effective oral treatment option for this serious, chronic disease.”
All key secondary efficacy endpoints showed statistically significant improvements for patients treated with Zeposia compared to placebo at Week 10 and Week 52. Findings include:
Induction Period (Week 10)
At Week 10, key secondary endpoints were highly statistically significant and showed more patients treated with Zeposia achieved clinical response, endoscopic improvement and mucosal healing compared to placebo.
In patients with prior TNF-inhibitor exposure, clinical remission results favored Zeposia over placebo, but findings were not significant at Week 10. A nominally statistically significant difference was observed for clinical response (p=0.008).
Maintenance Period (Week 52)
At Week 52, highly statistically significant results were achieved for patients treated with Zeposia compared to placebo, including clinical response, endoscopic improvement, maintenance of remission, corticosteroid-free remission, mucosal healing and durable remission.
Clinical remission and response improved with Zeposia regardless of previous TNF-inhibitor use at Week 52.
In the induction period, the most common treatment-emergent adverse events (TEAEs) for patients who received Zeposia versus placebo, respectively, were anemia (4.2% vs 5.6%), nasopharyngitis (3.5% vs 1.4%) and headache (3.3% vs 1.9%). In the maintenance period, the most common TEAEs for Zeposia versus placebo, respectively, were alanine aminotransferase increase (4.8% vs 0.4%; no serious events), and headache (3.5% vs 0.4%).
“These Zeposia True North results represent a meaningful achievement for patients living with ulcerative colitis, many of whom have an inadequate response or do not respond at all to currently available therapies,” said Mary Beth Harler, M.D., head of Immunology and Fibrosis Development, Bristol Myers Squibb. “We look forward to working with health authorities to bring Zeposia to this patient population and remain committed to pursuing new scientific advances to help deliver transformational medicines for the gastroenterology community.”
Virtual Investor Event
Bristol Myers Squibb will host a virtual Investor Event on Monday, October 12, 2020 at 8:00 a.m. EDT to discuss the Zeposia Phase 3 True Northdata presented at UEG Week Virtual 2020. Company executives will provide an overview of data presented and address questions from investors and analysts.
Investors and the general public are invited to listen to a live webcast at http://investor.bms.com or by calling the U.S. toll free at 1-800-458-4121 or international +1 313-209-6672, confirmation code: 9071827, or using this link, which becomes active 15 minutes prior to the scheduled start time and entering your information to be connected. Materials related to the webcast will be available at the same website prior to the event. An archived edition of the session will be available later that day.
About True North
True North is a Phase 3, multicenter, randomized, double-blind, placebo-controlled trial comparing the efficacy and safety of Zeposia 1mg in patients with moderate to severe ulcerative colitis who did not adequately respond to prior treatment. In the induction phase, a total of 645 patients were randomized to receive Zeposia (n=429) or placebo (n=216), of whom 94% and 89%, respectively, completed the induction period. At study entry, mean age was 42 years, 60% were male and mean disease duration was 7 years; patient characteristics were well-balanced across treatment groups. Cohort 1 patients were randomized 2:1 to Zeposia or placebo and treated once daily for 10 weeks. Cohort 2 (n=367) was an open-label arm, and included to allow adequate patient numbers for the maintenance phase of the trial. Cohort 2 patients were treated once daily with Zeposia for 10 weeks.
For the maintenance phase, 457 patients were re-randomized to maintenance treatment with either Zeposia (n=230) or placebo (n=227). Of these, 80% and 54.6% of patients who received Zeposia and placebo, respectively, completed the study; disease relapse (13.5% Zeposia, 33.9% placebo) was the most common reason for discontinuation. Patients on Zeposia from either Cohort 1 or 2 who achieved clinical response in the induction phase at Week 10 were re-randomized 1:1 to Zeposia or placebo through Week 52. Patients on placebo who achieved clinical response in the induction phase at Week 10 remained on placebo during this blinded maintenance phase.
In Cohort 1 of the induction phase and in the re-randomized patient group in the maintenance phase, 30% of patients had prior TNF-inhibitor exposure.
All eligible patients were rolled into an open-label extension trial, which is ongoing and designed to assess the longer-term profile of Zeposia for the treatment of moderate to severe ulcerative colitis.
The primary endpoints in True North are the proportion of patients in clinical remission based on a composite clinical and endoscopic score (3-component Mayo Score) at Week 10 in the induction phase, and at Week 52 for the maintenance phase. Secondary endpoints include the proportion of patients achieving clinical response at Week 10 and Week 52, the proportion of patients with endoscopic improvement (endoscopy score ≤1) at Week 10 and Week 52, the proportion of patients with mucosal healing at Week 10 and Week 52, and clinical remission at Week 52 in patients that were in remission at Week 10. In this study, mucosal healing is defined as endoscopic improvement with histologic remission. More information can be found on www.clinicaltrials.gov, NCT02435992.
Topline results from True North were previously announced in June 2020.
About Ulcerative Colitis
Ulcerative colitis, a chronic inflammatory bowel disease (IBD), is characterized by an abnormal, prolonged immune response that creates long-lasting inflammation and ulcers (sores) in the mucosa (lining) of the large intestine (colon) or rectum. Symptoms, including bloody stools, severe diarrhea and frequent abdominal pain, usually develop over time rather than suddenly. Ulcerative colitis has a major impact on patients’ health-related quality of life, including physical functioning, social and emotional well-being and ability to work. Many patients have an inadequate response or do not respond at all to currently available therapies. It is estimated that approximately 12.6 million people worldwide have IBD.
About Zeposia (ozanimod)
Zeposia (ozanimod) is an oral, sphingosine-1-phosphate (S1P) receptor modulator that binds with high affinity to S1P receptors 1 and 5. Zeposia reduces the capacity of lymphocytes to exit from lymph nodes, reducing the number of circulating lymphocytes in peripheral blood. The mechanism by which Zeposia exerts therapeutic effects in ulcerative colitis is unknown but may involve the reduction of lymphocyte migration into the inflamed intestinal mucosa.
The U.S. Food and Drug Administration (FDA) approved Zeposia for the treatment of adults with relapsing forms of multiple sclerosis (RMS) in March 2020.The European Commission approved Zeposia for the treatment of adult patients with relapsing remitting multiple sclerosis (RRMS) with active disease as defined by clinical or imaging features in May 2020. Bristol Myers Squibb is also investigating Zeposia forthe treatment of moderately to severely active Crohn’s disease in the ongoing Phase 3 YELLOWSTONE clinical trial program.
U.S. FDA-APPROVED INDICATION FOR ZEPOSIA
ZEPOSIA is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.
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