Bristol Myers Squibb’s Phase III Clinical Trial for Zeposia Fails to Meet Primary Endpoint of Clinical Remission in Crohn Disease

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Bristol Myers Squibb (BMS) revealed that despite its safety profile remaining consistent with previous studies, the Phase III YELLOWSTONE clinical trial evaluating Zeposia (ozanimod) did not meet its primary endpoint of clinical remission for moderate to severe active Crohn disease in adults after 12 weeks. Despite the unexpected setback, the organization stated that it plans to continue improving its research, providing a full evaluation of the YELLOWSTONE trial and share the trial data in the future. According to a press release, the trial is an evaluation of Zeposia's safety and efficacy, encompassing two induction studies, a maintenance study, and an open-label extension, involving doses of 0.92 mg (equivalent to 1 mg).¹

“To date, no S1P modulator has shown an effect in a Phase III trial in Crohn’s disease, where a high unmet medical need remains for new therapies that offer more patients relief from symptoms and the potential for remission,” said Roland Chen, MD, SVP, head, immunology, cardiovascular and neuroscience development, BMS, in the press release. “While we are disappointed that the primary endpoint was not reached in this first induction trial, we are committed to driving transformative science on behalf of individuals with immune-mediated diseases and would like to thank the investigators and patients who are participating in the YELLOWSTONE clinical trial program.”

At the end of last month, BMS announced positive results from its Phase III DAYBREAK study of Zeposia for relapsing forms of multiple sclerosis (MS). As part of the trial, 2,494 participants were exposed to the treatment for a total of 61 months. According to a company press release, three- and six-month confirmed disability progression was absent in 82.8% and 84.8% of participants in the trial, respectively.^2,3

“Currently no cure exists for multiple sclerosis, but effective strategies and treatments can help slow disease progression and alleviate symptoms,” said Jonathan Sadeh, MD, MSc, SVP, head of global program leaders, immunology, cardiovascular and neuroscience development, BMS, in a press release. “These DAYBREAK efficacy, safety and rebound data underscore a consistent and sustained safety and efficacy profile and add to the body of evidence supporting Zeposia’s role in the treatment armamentarium. We remain focused on advancing care and delivering meaningful innovations in neuroscience, including for the millions of people impacted by relapsing forms of multiple sclerosis.”

Common symptoms of Crohn disease include abdominal pain, malnutrition, diarrhea, cramping, and weight loss. It is most common in adolescents and young adults between the ages of 15-35 years. According to Healthline, it may affect close to 780,000 people in the United States.⁴

“During the years 2003 to 2013, there was no significant change in the hospitalization rate when Crohn’s disease was the primary diagnosis,” Healthline reported. “The hospitalization rate, however, increased significantly during this period when Crohn’s disease was the secondary diagnosis, rising from more than 120,000 hospital stays in 2003 to more than 196,000 in 2013.”

References

1. Bristol Myers Squibb Provides Update on the First Phase 3 YELLOWSTONE Trial Evaluating Oral Zeposia (ozanimod) in Patients with Moderate to Severe Active Crohn’s Disease. BMS. March 28, 2024. Accessed March 29, 2024. https://news.bms.com/news/corporate-financial/2024/Bristol-Myers-Squibb-Provides-Update-on-the-First-Phase-3-YELLOWSTONE-Trial-Evaluating-Oral-Zeposia-ozanimod-in-Patients-with-Moderate-to-Severe-Active-Crohns-Disease/default.aspx

2. Bristol Myers Squibb Reveals Promising Results from Trial of Zeposia for Multiple Sclerosis. Pharmaceutical Executive. March 1, 2024. Accessed March 29, 2024. https://www.pharmexec.com/view/bristol-myers-squibb-reveals-promising-results-from-trial-of-zeposia-for-multiple-sclerosis

3. Bristol Myers Squibb Announces New Data from the Long-Term DAYBREAK Study Reinforcing Efficacy and Safety of Zeposia (ozanimod) in Patients with Relapsing Forms of Multiple Sclerosis. BMS. February 29, 2024. Accessed March 29, 2024. https://news.bms.com/news/corporate-financial/2024/Bristol-Myers-Squibb-Announces-New-Data-from-the-Long-Term-DAYBREAK-Study-Reinforcing-Efficacy-and-Safety-of-Zeposia-ozanimod-in-Patients-with-Relapsing-Forms-of-Multiple-Sclerosis/default.aspx

4. Crohn’s Disease: Facts, Statistics, and You. Healthline. Accessed March 29, 2024. https://www.healthline.com/health/crohns-disease/facts-statistics-infographic#Causes