DOP052 Etrasimod as induction and maintenance therapy in Asian patients with moderately to severely active Ulcerative Colitis: Results from the maintenance period of a randomised, double-blind, placebo-controlled, multi-centre Phase 3 study (ES101002)
Authors: Wu K , Zheng C , Cao Q , Gao X , Ding Y , Zhong J , Zhang H , Wang X , Wang B , Zhang Z , Wang N , Cao X , Ye L , Liang J , Liu X , Zhou Y , Chiu C T , Kim T O , Chou J W , Xu B , Shen X , Chen D , Chen W C , Liu Y , Shen J , Liu F , Zhan Q , Ding X , Zeng S , Lin Y , Ying L , Chen X 
Published: January 2025

Background

Etrasimod (ETR) is an oral, once daily (qd), selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). ES101002 was a registrational Phase (Ph) 3 study evaluating the efficacy and safety of ETR in Asian patients (pts) with moderately to severely active UC (NCT04176588). ETR has shown significant benefit vs placebo (PBO) as induction and maintenance therapy in pts with UC, including in the 12-week (wk) induction period (IP) of ES101002.1–4 Here, we report results from the 40-wk maintenance period (MP) of ES101002.

Methods

The study comprised a 12-wk IP, 40-wk MP, and open-label (OL) period (up to 40 wks). Eligible pts were enrolled from the Chinese mainland, Taiwan, and South Korea, had confirmed moderately to severely active UC, and had failed ≥1 UC treatment (conventional and/or biologics/JAK inhibitors). Pts randomised 2:1 into the IP received ETR 2 mg qd or PBO for 12 wks. Clinical responders at wk 12 were re-randomised 1:1 into the MP and received ETR or PBO for 40 wks. In the MP, stratification factors were treatment in the IP, previous exposure to biologics/JAK inhibitors, and concomitant use of corticosteroids at IP baseline. IP non-responders or pts who experienced UC worsening in IP/MP were offered entrance into the OL period. The objectives for the MP of the study were to evaluate the efficacy and safety of ETR vs PBO.

Results

A total of 158 pts were randomised into the MP and received treatment (77 ETR; 81 PBO). Baseline pt demographics and disease characteristics, including mean age (43.8 years [yrs] ETR; 40.7 yrs PBO), proportion of female pts (45.5% ETR; 40.0% PBO), and mean baseline modified Mayo Score (6.0 ETR; 5.8 PBO), were balanced between groups. A higher proportion of pts receiving ETR (89.6%) vs PBO (51.9%) completed the 40-wk MP. All efficacy objectives in the 40-wk MP were achieved (Figure 1). A significantly greater proportion of pts receiving ETR vs PBO achieved clinical remission, clinical response, endoscopic improvement, endoscopic normalisation, mucosal healing, and symptomatic remission (P&lt;.0001 each). Most treatment-emergent adverse events (TEAEs) were mild to moderate in severity (Table 1). ETR vs PBO resulted in fewer Grade 3 TEAEs (ETR 10.4%, PBO 13.6%) and serious adverse events (ETR 7.8%, PBO 8.6%). In each group, there was a single treatment discontinuation due to a TEAE (UC worsening) with no Grade 4 TEAEs or deaths.

Conclusion

Consistent with previous studies, ETR resulted in clinically meaningful and statistically significant improvement of UC in Asian pts across clinical, endoscopic, and histologic endpoints, and was safe and well-tolerated.

References

1.Sandborn WJ, Peyrin-Biroulet L, Zhang J, et al. Efficacy and Safety of Etrasimod in a Phase 2 Randomized Trial of Patients With Ulcerative Colitis. Gastroenterology. 2020;158:550-561.

2.Sandborn WJ, Vermeire S, Peyrin-Biroulet L, et al. Etrasimod as induction and maintenance therapy for ulcerative colitis (ELEVATE): two randomised, double-blind, placebo-controlled, phase 3 studies. Lancet. 2023;401:1159-1171.

3.Vermeire S, Chiorean M, Panés J, et al. Long-term Safety and Efficacy of Etrasimod for Ulcerative Colitis: Results from the Open-label Extension of the OASIS Study. J Crohns Colitis. 2021;15:950-959.

4.Wu K, Zhang Z, Ding Y, et al. P1750: Efficacy and safety of etrasimod induction therapy in Asia patients with moderately to severely active ulcerative colitis: Results from the 12-week induction period of a Phase 3, randomized, placebo-controlled, double-blind, multicenter, China registrational study (ES101002). Presented at: United European Gastroenterology; October 15, 2024.