S1P modulator disappoints in Crohn’s disease phase 3 study


By Michael Woodhead

2 Apr 2024

The S1P modulator ozanimod has delivered ‘disappointing’ results in people with Crohn’s disease, according to the preliminary analysis of a phase 3 trial.

Study sponsor Bristol Myers Squibb announced on 28 March (link here) that the YELLOWSTONE trial evaluating oral ozanimod (Zeposia) did not meet its primary endpoint of clinical remission at week 12 of the induction phase of the study.

The international clinical trial  – including Australian centres – consists of two 12-week induction studies involving approximately 600 patients with moderate to severe active Crohn’s disease who are treated with 1mg ozanimod or placebo.

The YELLOWSTONE study (link here) population was adults who have endoscopically-confirmed Crohn’s disease for at least three months and who have not improved on or have not been able to tolerate, at least one prior Crohn’s disease medication such as corticosteroids or immunomodulators.

Nonresponders, those with disease relapse during maintenance, and completers of the maintenance study have the option to enrol in the open-label extension trial.

However the sponsor has released initial results showing that the active treatment group did not meet the primary endpoint of the proportion of patients with a Crohn’s Disease Activity Index (CDAI) score of less than 150.

The co-primary endpoints of the maintenance study are the proportion of patients with a CDAI score of less than 150 and the proportion of patients with a Simple Endoscopic Score for Crohn’s disease (SES-CD) score decrease from baseline of at least 50%.

“To date, no S1P modulator has shown an effect in a Phase 3 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 Dr Roland Chen, senior vice president and head, Immunology, Cardiovascular and Neuroscience development, Bristol Myers Squibb.

He said the safety profile of ozanimod in the study was consistent with that observed in previously reported trials.

Dr Chen added that the company will complete a full evaluation of the YELLOWSTONE trial data and work with investigators to share the results with the scientific community in the future.

“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.”

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