Novel agent VTX002 holds promise in ulcerative colitis

The investigational, oral, selective, sphingosine-1-phosphate-1 (S1P1) receptor modulator VTX002 was associated with increased clinical, endoscopic, and histologic remission rates compared with placebo in patients with moderately to severely active ulcerative colitis (UC) in a phase 2 study. Moreover, the agent was well tolerated in this study population.

“Various S1P receptor modulators have been approved for the treatment of multiple sclerosis and/or UC, with ozanimod and etrasimod being available agents in UC,” outlined Prof. Bruce Sands (Icahn School of Medicine at Mount Sinai, NY, USA) [1]. VTX002 is a novel S1P1 receptor modulator, with a different receptor selectivity than ozanimod and etrasimod.

In a multicentre, randomised, double-blind phase 2 trial (NCT05156125), Prof. Sands and colleagues tested VTX002 in patients with moderately to severely active UC. The participants (n=213) were randomised 1:1:1 to 60 mg VTX002 once daily, 30 mg VTX002 once daily, or a placebo. The primary endpoint was clinical remission (defined as modified Mayo score [MMS] stool frequency subscore ≤1, rectal bleeding subscore =0, and endoscopic subscore ≤1) at week 13.

In the 60 mg and 30 mg VTX002 arms, 27.9% and 23.9% of the participants achieved clinical remission by week 13, respectively; in the placebo arm, 11.4% achieved this endpoint. These findings significantly favoured the experimental arms over the placebo arm (P=0.018; P=0.041). Notably, the effect appeared to be present regardless of experience with advanced therapies.

Secondary efficacy endpoints, such as endoscopic improvement (36.8%; 32.4%; 15.7%), histologic remission (19.1%; 28.2%; 7.1%), and symptomatic remission (42.6%; 40.8%; 25.7%) all favoured the experimental arms over the placebo arm.

“The novel agent was generally well tolerated,” stated Prof. Sands. The rate of adverse events (AEs) was somewhat higher in the experimental arms than in the placebo arm (47% vs 34.3%), but the rate of serious AEs was low with 2.7% and 4.3% in the 60 mg arm and 30 mg arm, respectively. “Finally, there were no cases of bradycardia, atrioventricular block, serious infections, macular oedema, or death,” Prof. Sands noted.

In conclusion, VTX002 was associated with improved health outcomes compared with placebo and had an acceptable safety profile in a population of patients with moderately to severely active UC.

1. Sands BE, et al. Efficacy and safety of the oral selective sphingosine-1-phosphate-1 receptor modulator VTX002 in moderately to severely active ulcerative colitis: results from a randomised, double-blind, placebo-controlled, phase 2 trial. OP03, 19^th Congress of ECCO, 21–24 February 2024, Stockholm, Sweden.

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Posted on 18 April, 2024