Introduction

Tumor necrosis factor–like cytokine 1A (TL1A) is a regulator of inflammation and fibrosis in inflammatory bowel disease. Tulisokibart, an anti-TL1A monoclonal antibody, demonstrated efficacy without clinically meaningful safety findings vs placebo after a 12-week induction period in adults with moderately to severely active UC in the phase 2 ARTEMIS-UC study.¹ We report long-term efficacy and safety of tulisokibart among cohort 1 induction responders from the open-label extension (OLE) period of ARTEMIS-UC.

Aims & Methods

ARTEMIS-UC was a phase 2, multicenter, double-blind, placebo-controlled study of tulisokibart in patients with moderately to severely active UC. Cohort 1 enrolled patients regardless of genetic-based diagnostic test (Dx) status whereas cohort 2 enrolled only Dx-positive patients. Patients were randomized to receive intravenous (IV) tulisokibart 1000 mg on day 1 and 500 mg at weeks 2, 6, and 10 or placebo; after the 12-week induction period, all participants had the option to continue in the OLE period. Participants were classified as induction responders (defined as reduction of ≥2 points and ≥30% in modified Mayo score from baseline, accompanied by a reduction ≥1 in rectal bleeding subscore or absolute rectal bleeding subscore ≤1 at week 12) or induction nonresponders. Cohort 1 induction responders in the tulisokibart group were randomized (stratified by Dx status) to receive open-label IV tulisokibart 100 mg or 250 mg every 4 weeks at week 14 until week 170. We report data from cohort 1 through week 50 of the OLE period: clinical and endoscopic efficacy outcomes and biomarkers through week 50 are reported for cohort 1 induction responders from the tulisokibart group whereas safety through week 50 are reported for cohort 1 induction responders from both the tulisokibart group and the placebo group. Descriptive statistics were used to summarize observed data.

Results

47 of 68 tulisokibart-treated patients in cohort 1 were induction responders and were randomized to receive tulisokibart 250 mg (n = 25) or 100 mg (n = 22). Improvements in clinical, endoscopic, and biomarker outcomes observed with tulisokibart were generally maintained through week 50 in both dose groups (Table). However, at week 50, a greater proportion of patients achieved clinical and endoscopic outcomes with tulisokibart 250 mg vs 100 mg. In the safety population, (tulisokibart 250 mg, n = 35; 100 mg, n = 30), through week 50, AEs occurred in 63% and 77% of patients receiving tulisokibart 250 mg and 100 mg, respectively; most were mild to moderate in severity. Serious AEs occurred in 1 patient (3%) and two patients (7%) in the tulisokibart 250 mg and 100 mg groups, respectively.

Conclusion

At week 50, maintenance of treatment effect was generally observed in cohort 1 induction responders in the tulisokibart group. A trend for higher efficacy with tulisokibart 250 mg vs 100 mg maintenance treatment was observed at week 50. Tulisokibart was well tolerated with no identified safety signals. Larger trials are needed to confirm these findings.

References

1. Sands B, et al. J Crohns Colitis. 2023;17(Supplement_1):i56-i59.

Disclosure

CM has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, BioJAMP, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Pendopharm, Pfizer, Prometheus Biosciences Inc., Roche, Sanofi, and Takeda; speaker’s fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, Bristol Myers Squibb, Ferring, Fresenius Kabi, Janssen, Pendopharm, Pfizer, and Takeda; royalties from Springer Publishing; and research support from Ferring and Pfizer.
SH has received advisory fees from Eli Lilly and Tilotts.
MPS has received educational grants or research support from Gilead and Celltrion, speakers fees from Janssen, AbbVie, Ferring, Takeda, Pfizer, Shire, Celltrion, Eli-Lilly and Dr. Falk Pharma, and has served on advisory boards for Janssen, Takeda, Pfizer, Celgene, AbbVie, MSD, Emerge Health, Gilead, BMS, Celltrion, and Eli-Lilly.
JKA, MY, and BD are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA
BGF is a consultant for AbbVie, AbolerIS, AgomAB Therapeutics, Allianthera, Amgen, AnaptysBio, Applied Molecular Transport Inc., Arena Pharma, Atomwise, Avoro Capital Advisors, BioJamp, Biora Therapeutics, Boehringer Ingelheim, Boxer, Bristol Myers Squibb/Celgene, Celsius Therapeutics, Connect BioPharma, Cytoki, Disc Medicine, Duality, EcoR1 Capital, Equillium, Ermium, First Wave, First Word Group, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, GlaxoSmithKline, Gossamer Pharma, Hinge Bio, Hot Spot Therapeutics, Imhotex, Immunic Therapeutics, InDex Pharmaceuticals, JAKAcademy, Janssen, Japan Tobacco Inc., Kaleido Biosciences, Landos Biopharma, Leadiant, L.E.K. Consulting, Lenczner Slaght, LifeSci Capital, Lilly, Lument AB, Millennium, MiroBio, Morgan Lewis, Morphic Therapeutics, Mylan, OM Pharma, Origo BioPharma, Orphagen, Pandion Therapeutics, Pendopharm, Pfizer, Play to Know AG, Prometheus Therapeutics and Diagnostics, Progenity, Protagonist, PTM Therapeutics, Q32 Bio, Rebiotix, REDX, Roche, Sandoz, Sanofi, Seres Therapeutics, Silverback Therapeutics, Surrozen Inc., Takeda, Teva, Thelium, Tigenix, Tillotts, Ventyx Biosciences, VHSquared Ltd., Viatris, Ysios, Ysopia, and Zealand Pharma; on the Speakers’ Bureau for AbbVie, Janssen, and Takeda; and on advisory boards for AbbVie, Amgen, AMT, AnaptysBio, Axio Research, Boehringer Ingelheim, Bristol Myers Squibb/Celgene, EcoR1 Capital, Genentech/Roche, GlaxoSmithKline, InDex Pharmaceuticals, Janssen, Lilly, MiroBio, Morphic, Origo BioPharma, Pfizer, Progenity, Prometheus, REDX Pharma, Sanofi, Takeda, Teva, and Tillotts Pharma.
BES reports consulting fees from AbbVie, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, Artugen Therapeutics, Astra Zeneca, Biolojic Design, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Calibr, Celgene, Celltrion, ClostraBio, Equillium, Enthera, Envied Biosciences, Evommune, Ferring, Fresenius Kabi, Fiat, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Imhotex, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Kaleido, Kallyope, Merck, Microba, Mobius Care, Morphic Therapeutics, MRM Health, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Therapeutics, Reistone Biopharma, Sanofi, Spyre Therapeutics, Sun Pharma, Surrozen, Target RWE,Teva, TLL Pharmaceutical, Tr1X, Union Therapeutics, Ventyx Biosciences; consulting and speaking fees from Abivax; consulting and speaking fees and other support from Lilly; research grants, consulting and speaking fees and other support from Bristol Myers Squibb, Janssen, Pfizer, Takeda; research grants and consulting fees from Theravance Biopharma; and stock/stock options from Ventyx Biopharma.