For the first time, a new class of biologic drugs is showing real promise for patients with Crohn’s disease who have run out of options.
Story Snapshot
- Novel anti-TL1A antibodies are demonstrating significant efficacy in moderate-to-severe Crohn’s disease.
- Multiple companies, including Merck, Teva, Sanofi, and Earendil Labs, are advancing these therapies through clinical trials.
- These drugs target TL1A, a cytokine linked to both inflammation and fibrosis, offering a new mechanism distinct from current biologics.
- Early results show benefit even in patients who failed previous biologic treatments.
- The field is rapidly evolving, with several candidates in Phase 1–3 trials and the potential to reshape IBD therapy.
The Problem with Current Crohn’s Treatments
For decades, Crohn’s disease management has relied on corticosteroids, immunomodulators, and biologics targeting TNF-α or integrins. While these therapies have improved outcomes, many patients experience inadequate response or lose efficacy over time. The high rate of treatment failure and side effects has created a pressing need for new approaches. Existing biologics often fail to address the underlying fibrosis that drives disease progression, leaving patients vulnerable to complications and surgeries.
Patients who do not respond to current therapies face a bleak outlook, with limited options and declining quality of life. The search for more effective, safer, and convenient treatments has been a top priority for both patients and clinicians.
Watch: #MondayNightIBD IBD Clinical Trials to Watch: Anti-TL1As & mir124 enhancers
TL1A: A New Target in the Fight Against Crohn’s
TL1A, a cytokine implicated in intestinal inflammation and fibrosis, has emerged as a promising therapeutic target. Unlike TNF-α or integrins, TL1A plays a role in both the inflammatory and fibrotic processes that characterize Crohn’s disease. By targeting TL1A, new monoclonal antibodies aim to address the root causes of disease progression, not just symptoms. This first-in-class mechanism represents a significant departure from existing therapies and offers hope for patients who have exhausted other options.
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Clinical Trial Results: What We Know So Far
Recent clinical trials have yielded encouraging results. In February 2025, Teva and Sanofi presented positive Phase 2b data for duvakitug at ECCO 2025, showing significant clinical remission and endoscopic response rates in Crohn’s disease and ulcerative colitis. Merck has expanded its tulisokibart program to include additional immune-mediated diseases, with Phase 3 trials ongoing for Crohn’s disease. Earendil Labs completed the first cohort dosing in a Phase 1 trial of HXN-1001, a half-life extended anti-TL1A antibody, and Spyre Therapeutics reported interim Phase 1 results for SPY072, suggesting potential for infrequent maintenance dosing.
The Road Ahead: Implications
The emergence of anti-TL1A antibodies could shift the treatment paradigm for Crohn’s disease and other immune-mediated conditions. If long-term safety and efficacy are confirmed, these therapies may become first-line options for patients with moderate-to-severe disease. The potential to reduce hospitalizations and surgeries could also lower healthcare costs and improve quality of life.
Sources:
Earendil Labs press release (HXN-1001)
PubMed: Tulisokibart Phase 2a study
