CULTIVATE: Promising signal for etrasimod in Crohn’s disease

Etrasimod was associated with favourable efficacy outcomes and tolerability in participants with moderately to severely active Crohn’s disease (CD) in the extension period of a phase 2 trial. Later-phase studies are needed to further explore the potential of etrasimod in the CD population.

The selective S1P receptor modulator etrasimod was tested in the seamless phase 2/3 CULTIVATE trial (NCT04173273) among participants with moderately to severely active CD. Prof. Geert D’Haens (Amsterdam University Medical Center, the Netherlands) presented data from the extension phase of substudy A [1]. Substudy A was a phase 2 study within the CULTIVATE trial, consisting of a 14-week induction period followed by a 52-week maintenance and extension period.

In this substudy, 65 participants who were refractory to at least 1 CD therapy were randomised 1:1 to etrasimod 2 mg or 3 mg daily. After 14 weeks, non-responders were re-randomised to the 2 or 3 mg arm. This analysis primarily assessed the endoscopic response after 52 weeks of therapy. An endoscopic response was defined as endoscopic remission or at least a 50% reduction in Simple Endoscopic Score for CD (SES-CD).

In the treat-through analysis, 19.5% of the participants in the 3 mg arm and 14.3% of those in the 2 mg arm achieved an endoscopic response. Furthermore, clinical remission, according to Crohn's Disease Activity Index (CDAI), was reached by 34.1% and 28.6% of the participants in the 3 mg and 2 mg arms, respectively. Also, clinical remission according to the patient-reported outcome (PRO2) questionnaire was observed in 36.6% and 19% of the participants.

“Etrasimod was well tolerated,” highlighted Prof. D’Haens. The most common treatment-emergent adverse events in the 2 mg and 3 mg arms were worsening of CD (25% and 21.6%, respectively), headache (10.7% and 16.2%), arthralgia (10.7% and 13.5%), and COVID-19 (10.7% and 24.3%). “Severe infections were seen in 3.6% and 5.4% of the participants in the 2 and 3 mg arms,” added Prof. D’Haens. Finally, 2 participants in the 3 mg arm had a first-degree AV block, 1 participant in the 2 mg experienced bradycardia, and 1 participant in the 3 mg arm had hypertension.

“Etrasimod may be an effective agent in moderately to severely active CD, with higher efficacy at the 3 mg dose,” concluded Prof. D’Haens. “Further placebo-controlled studies are ongoing.”

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   1. D’Haens G, et al. Etrasimod for moderately to severely active Crohn’s disease: results from the extension period of a phase 2 study. LB06, UEG Week 2024, 12–15 October, Vienna, Austria.

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Posted on 28 November 2024