Pharmacological properties and clinical efficacy of sphingosine 1-phosphate (S1P) receptor modulator, Ozanimod (ZEPOSIA<sup>®</sup>)

Ozanimod hydrochloride (Product name: ZEPOZIA^® Capsule Starter Pack, ZEPOZIA^® Capsules 0.92 mg; Nonproprietary name: ozanimod hydrochloride, hereinafter referred to as ozanimod) is an orally available receptor modulator that acts on the sphingosine 1-phosphate (S1P) receptor and selectively binds with high affinity to S1P₁ and S1P₅ receptors. Following binding to and activation of S1P₁ receptors, ozanimod acts as a functional S1P₁ receptor antagonist by inducing internalization of S1P₁ receptors expressed on the surface of cells such as lymphocytes through agonism of S1P₁ receptors. These effects may ameliorate the pathologic changes of the autoimmune disease ulcerative colitis (UC). The Japanese phase II/III study (Study RPC01-3103) demonstrated the efficacy and safety of this drug in Japanese patients with moderate to severe ulcerative colitis. In Japan, it was approved by the Ministry of Health, Labour and Welfare (MHLW) in December 2024 for the treatment of moderate to severe UC in patients who have had an inadequate response to conventional therapies, and was launched in March 2025. Existing UC treatments show significant therapeutic effects, but medications for moderate to severe UC have respective advantages and disadvantages in efficacy, safety, and administration routes. No treatment meets all criteria. Ozanimod, with a novel mechanism, offers sustained high efficacy in improving clinical symptoms and mucosal damage in moderate to severe UC patients. It has a favorable safety profile, high medication compliance, and is a convenient oral treatment for long-term use. Thus, providing Ozanimod as a new UC treatment option is of high clinical significance.