Positive outcomes for etrasimod in UC

The small molecule etrasimod was evaluated in 2 phase 3 trials with a duration of 12 and 52 weeks in patients with moderate-to-severe ulcerative colitis (UC). Significant better results were seen in the etrasimod groups which included about 4 times higher clinical remission rates at year 1.

Etrasimod is a selective sphingosine-1-phospate-receptor modulator that is currently evaluated for various immuno-inflammatory indications. Newly reported was data on ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369), 2 phase 3 trials on UC that were conducted by Prof. William J Sandborn (University of California San Diego, CA, USA) and colleagues [1].

Participating adults in both studies suffered from moderate-to-severe UC defined by activity measures of a modified Mayo Score of 4‒9, plus a centrally read endoscopic subscore ≥2 beside a rectal bleeding subscore ≥1. In line with the previous history at baseline, the assessment was stratified according to the type of prior treatments and corticosteroid medication. The 2 trials randomised 354 (ELEVATE UC 12) and 433 (ELEVATE UC 52) patients 2:1 to the study drug groups with a regimen of 2 mg of etrasimod once daily or placebo. Between 61.8% and 62.9% of the patients in both studies had never received biologics or Janus kinase inhibitors before. While ELEVATE UC 12 involved a 12-week induction only setting, the design of ELEVATE UC 52 foresaw a 40-week period of therapy subsequent to induction over 12 weeks. Change to a currently still ongoing open-label extension trial (ELEVATE UC OLE; NCT03950232) was available for patients with treatment failure at week 12.

The presented results revealed that etrasimod met all its primary and secondary efficacy endpoints in both studies. The rate for the primary endpoint of clinical remission in ELEVATE UC 12 was 24.8% for etrasimod versus 15.2% for placebo (P=0.026). The respective outcomes in ELEVATE UC 52 were 27% versus 7.4% after 3 months and even higher after 1 year with 32.1% versus 6.7% (P˂0.001 for both comparisons). The secondary endpoints included: mucosal healing, endoscopic improvement, symptomatic remission, and sustained clinical remission.  Steroid-free remission was achieved in >4-fold more patients on etrasimod than on placebo (32.1% vs 6.7%; P<0.001).

The researchers pointed out that in both studies, treatment-emergent adverse events (AE) and serious AEs were similarly reported between treatment groups. They also highlighted that there were no serious AEs of bradycardia or atrioventricular block. The most common AEs in ELEVATE UC 52 were headache, nausea, and SARS-CoV-2 infection.

1. Sandborn WJ, et al. Etrasimod 2 mg once daily as treatment for moderately to severely active ulcerative colitis: results from the phase 3 ELEVATE UC 52 and ELEVATE UC 12 Lecture 968a, Digestive Disease Week 2022, 21‒24 May, San Diego, CA, USA.

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Posted on 14 June 20228 April 2024