Safety and efficacy of the anti-TL1A monoclonal antibody tulisokibart for Crohn's disease: a phase 2a induction trial
- PMID: 40456235
- DOI: 10.1016/S2468-1253(25)00071-8
Safety and efficacy of the anti-TL1A monoclonal antibody tulisokibart for Crohn's disease: a phase 2a induction trial
Erratum in
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Correction to Lancet Gastroenterol Hepatol 2025; 10: 715-25.Lancet Gastroenterol Hepatol. 2025 Aug;10(8):e10. doi: 10.1016/S2468-1253(25)00204-3. Lancet Gastroenterol Hepatol. 2025. PMID: 40651482 No abstract available.
Abstract
Background: TNF-like cytokine 1A (TL1A) is a key mediator of inflammation and fibrosis. The efficacy and safety of the anti-TL1A monoclonal antibody tulisokibart as induction treatment was assessed in adults with moderately to severely active Crohn's disease with a history of insufficient response, loss of response, or intolerance to conventional or approved biological therapies.
Methods: In the phase 2a, multicentre, open-label APOLLO-CD study, participants aged 18 years or older with moderately to severely active Crohn's disease, as defined by a Crohn's Disease Activity Index (CDAI) of 220-450 and a Simple Endoscopy Score for Crohn's Disease (SES-CD) of at least 6 for ileocolonic or colonic disease or at least 4 for isolated ileal disease, received intravenous tulisokibart (1000 mg on day 1 and 500 mg at weeks 2, 6, and 10). This Article reports the results of the primary analysis of the induction period. The primary endpoints were safety and the proportion of participants with endoscopic response at week 12, defined as a decrease in SES-CD of at least 50% from baseline. Safety was analysed in all participants treated with tulisokibart, and endoscopic response was analysed in the per-protocol analysis set, which included all participants treated with tulisokibart with baseline CDAI and SES-CD scores, except those with prespecified important protocol deviations. This trial is registered with ClinicalTrials.gov (NCT05013905) and is closed for recruitment; an open-label extension is ongoing.
Findings: Of 101 participants screened for eligibility, 55 eligible participants were enrolled and received tulisokibart. The mean age of participants was 39·1 years (SD 15·7), 34 (62%) were male, 21 (38%) were female, and 39 (71%) had received previous biological therapy. At week 12, endoscopic response was observed in 13 (26·0% [95% CI 15·9-39·6]) of 50 participants receiving tulisokibart in the per-protocol analysis set. Adverse events occurred in 43 (78%) of 55 participants, with most adverse events being mild to moderate in severity. The most frequently occurring adverse events (≥5% of participants) were COVID-19 (six [11%] participants), urinary tract infection (five [9%]), Crohn's disease (five [9%]), anaemia (four [7%]), nasopharyngitis (three [5%]), and fatigue (three [5%]). Eight (15%) participants had serious adverse events, none of which were considered related to the study drug by the investigator. There were no deaths.
Interpretation: This proof-of-concept study showed that tulisokibart is potentially efficacious in moderately to severely active Crohn's disease and is well tolerated. Randomised controlled trials with longer duration are needed to confirm these results; a double-blind, placebo-controlled, phase 3 trial is currently underway.
Funding: Prometheus Biosciences, a subsidiary of Merck & Co, Rahway, NJ, USA.
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Conflict of interest statement
Declaration of interests BGF declares consulting fees from AbbVie, Abivax, Adiso, AgomAB Therapeutics, Akros, Alira Health, Ally Bridge Group, AnaptysBio, Apini Therapeutics, Argenx, Avoro Capital Advisors, Belmore Law, BioFactura, BioJamp, Biora Therapeutics, Blackbird Laboratories, Boehringer-Ingelheim, Boxer Capital, Celsius Therapeutics, Celgene/BMS, Celltrion, Clarivate, Connect BioPharma, Disc Medicine, Duality, EcoR1, Eli Lilly, Ensho Therapeutics, Evida, Enveda, Faes Farma, First Wave, Forbion, Galapagos, Galen Atlantica, Genentech/Roche, General Atlantic, Genesis Therapeutics, Gilead, Gossamer Pharma, GSK, Imhotex, ImmiDomics, Immunic Therapeutics, Intercept, Janssen, Japan Tobacco, Klick Health, LifeMine Therapeutics, Mage Biologics, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Rahway, NJ, USA (MSD), Mestag, Mirador Therapeutics, Mobius, Monte Rosa Tx, Morphic Therapeutics, Nexys Therapeutics, Nighthawk Therapeutics, Nimbus Therapeutics, Novartis, OncoC4, OrbiMed, Orphagen, Pendopharm, Pfizer, Protagonist, 32 Bio, REDX, Roche, Roivant/Televant, Sanofi, Sobi, Sorriso, Spyre Therapeutics, Surrozen, Sun Pharma, Synedgen, Takeda, Teva, Triastek, Trex Bio, TR1X, TVM Lifesciences, Ventyx Biosciences, Versant Ventures, Vida Ventures, Zagbio; was a speaker for AbbVie, Janssen, and Takeda; is a member of scientific advisory board for AbbVie, AnaptysBio, Boehringer-Ingelheim, Celgene/BMS Eli Lilly, Genentech/Roche, Janssen, MSD, MiroBio, Origo BioPharma, Pfizer, REDX Pharma, Sanofi, Takeda, Teva, Ecor1Capital, Morphic, GSK; declares stock from Connect BioPharma, EnGene; declares expert testimony for Belmore Law; and is Senior Scientific Director for Alimentiv. BES declares travel fees from Eli Lilly and Company, Janssen Research & Development, Takeda Development Center Americas; grants from Janssen Research & Development and Bristol Myers Squibb; stock options in Ventyx Biosciences; consulting fees from AbbVie, Abivax, Adiso Therapeutics, Agomab Therapeutics, Alimentiv, Amgen, AnaptysBio, AstraZeneca, Biora Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion Healthcare, Ensho Therapeutics, Equilium, Eli Lilly and Company, Entera, Enveda Biosciences, Evommune, Ferring, Fzata, Galapagos, Genentech USA, Gilead Sciences, GlaxoSmithKline, GossamerBio, Imhotex, Immunic, Immunyx Pharma, Index Pharmaceuticals, Innovation Pharmaceuticals, Janssen Biotech, Janssen Scientific Affairs, Johnson & Johnson Health Care Systems, Kaleido, Kallyope, Kyowa Kirin, MSD, Microba, Microbiotica Limited, Mitsubishi Tanabe Pharma, Mobius Care, Morphic Therapeutic, MRM Health, Nexus Therapeutics, Immunyx Pharma, Nimbus Therapeutics, Odyssey Therapeutics, Pfizer, Progenity, Prometheus Biosciences, Inc, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Pharma, Reistone Biotherapeutics, Sorriso Pharmaceuticals, Spyre Therapeutics, Surrozen, Takeda Pharmaceuticals International, Target RWE, Teva Branded Pharmaceutical Products R&D, Theravance Biopharma, TLL Pharmaceutical, TR1X, Union Therapeutics, Ventyx Biosciences; honoraria from AbbVie, Bristol Myers Squibb, Celltrion, Abivax, Pfizer, Eli Lilly and Company, Takeda, Janssen, Mitsubishi Tanabe Pharam, and MSD; advisory board for Agomab, Amgen; and medical writing or editorial support from AbbVie, Abivax, Bristol Myers Squibb, Celltrion, Eli Lilly and Company, Janssen, MSD, Pfizer, Ventyx Biosciences, Morphic Therapeutics, and Takeda. CAS declares consulting fees from AbbVie, BMS, Boomerang, Buhlmann, Johnson and Johnson, Lilly, Napo Pharmaceuticals, Pfizer, Prometheus Biosciences, Inc, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA Prometheus Labs, Roivant, Takeda, Trellus Health; has been a speaker for CME activities for AbbVie, Johnson and Johnson Pfizer, Takeda; declares grant support from AbbVie, Johnson and Johnson, Pfizer, Takeda; and declares license fees from Takeda. MCD declares consultant and advisor for AbbVie, Abivax, Astra Zeneca, Boehringer Ingelheim International Gmbh, Bristol Meyers Squibb, Celltrion, Eli Lilly and Company, F Hoffmann-La Roche, Janssen Pharmaceuticals, Johnson and Johnson, MSD, Pfizer, Prometheus Labs, Prometheus Biosciences, Inc, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA, Sanofi, Spyre, and Takeda Pharmaceuticals. RSL declares consulting fees from Pfizer and Sanofi; scientific advisory board membership for CJ Biosciences and Ancilia Biosciences; and reports grants from Boehringer Ingelheim. JS declares research support from Galapagos and Viatris; consulting fees from Pfizer, Janssen, Ferring, Fresenius, AbbVie, Galapagos, Celltrion, Pharmacosmos, and Pharmanovia; and speakers fees from Pfizer, AbbVie, Ferring, Falk, Takeda, Janssen, Fresenius, and Galapagos. OL, AL, JL, DDN, and FT are former employees of Prometheus Biosciences, Inc, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA. AL and DDN previously owned stock in Prometheus Biosciences. JL declares stock options in Merck & Co, Inc, Rahway, NJ, USA. DDN is a current employee of Spyre Therapeutics. EJM-E, HL, YW, IJ, RM, MY, and JKA are employees of MSD. EJM-E, HL, MY, and JKA are shareholders in Merck & Co, Inc, Rahway, NJ, USA. JB is faculty member at Cedars-Sinai Medical Center (Cedars-Sinai has the right to receive future royalty payments from Prometheus Biosciences, Inc, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA); is a former consultant for Prometheus Biosciences, Inc; and had stock from Prometheus Biosciences. MW declares grant support from Prometheus Biosciences, Inc, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA. SRT declares approved and pending patents related to TL1A; consulting fees from MSD; and had stock in Prometheus Biosciences. DPBM declares consulting fees from Takeda, Prometheus Biosciences, Inc, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA and MSD; issued patents for anti-TL1A therapy for Crohn's disease and ulcerative colitis; and had stock in Prometheus Biosciences. All other authors declare no competing interests.
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