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Deucravacitinib does not meet primary endpoint for ulcerative colitis

Presented by
Prof. Silvio Danese, Vita-Salute San Raffaele University, Italy
ECCO 2022
Deucravacitinib did not significantly improve response rates or clinical remission rates in participants with active ulcerative colitis (UC) compared with placebo. Pharmacodynamical data of the phase 2 LATTICE-UC trial showed that the target tyrosine kinase 2 (TYK2) was hit but that the dose may have been insufficient to reduce inflammation in participants with UC. Another phase 2 trial has been initiated to investigate a higher dose of deucravacitinib.

Deucravacitinib is an oral, selective TYK2 inhibitor. The randomised, double-blind, placebo-controlled phase 2 LATTICE-UC trial (NCT03934216) was conducted to assess the safety and efficacy of this agent in patients with active UC. In total, 131 participants with moderately to severely active UC who failed at least 1 prior therapy were randomised 2:1 to 6 mg deucravacitinib twice daily (n=88), or placebo (n=43). The primary endpoint was clinical remissiona. Prof. Silvio Danese (Vita-Salute San Raffaele University, Italy) presented the results [1].

At week 12, the primary endpoint was not met. Clinical remission was achieved by 14.8% of the participants in the deucravacitinib arm and by 16.3% of the participants in the placebo arm (P=0.59). In participants who had failed on 1 or more prior biologic therapies, proportion of participants achieving clinical remission was 16.1%.

Deucravacitinib was well tolerated in the LATTICE-UC trial and the safety profile was consistent to deucravacitinib’s safety profiles in psoriasis trials. Adverse events (AEs) were reported in 70.1% and 47.6% of the participants in the experimental arm and placebo arm, respectively. Serious AEs were observed in 9.2% of the participants in the deucravacitinib arm and 4.8% of the participants in the placebo arm. Rash (11.5%), acne (9.2%), and UC (6.9%) were the most common AEs in participants treated with deucravacitinib.

Prof. Danese mentioned that pharmacological data showed that TYK2 engagement was observed without a subsequent effect on downstream inflammatory markers. According to Prof. Danese, this result suggests that the deucravacitinib dosing may have been too low to translate into clinical benefits for the participants. Therefore, another phase 2 trial (NCT04613518) is currently ongoing to investigate a higher dose of deucravacitinib in patients with UC.

a. Clinical remission is defined as modified Mayo score with subscores of stool frequency ≤1 with ≥1-point decrease from baseline, rectal bleeding of 0, and endoscopic subscore ≤1 excluding friability

  1. Danese S, et al. Efficacy and safety of deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in patients with moderately-to-severely active Ulcerative Colitis: 12-week results from the Phase 2 LATTICE-UC study. DOP42, ECCO 2022, 16–19 February.

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