Merck's Tulisokibart Claims Historic Phase 3 Victory in Ulcerative Colitis, Validating $10.8B Prometheus Buyout
On June 22, 2026, Merck announced positive topline results from its Phase 3 ATLAS-UC induction-only study (Study 2) evaluating tulisokibart (MK-7240) in patients with moderately to severely active ulcerative colitis (UC). The study successfully met its primary endpoint of clinical remission at Week 12 according to the Modified Mayo Score (MMS), along with all key secondary endpoints.
This milestone marks a major breakthrough as tulisokibart becomes the first anti-TL1A (tumor necrosis factor-like cytokine 1A) monoclonal antibody to demonstrate Phase 3 clinical efficacy, positioning Merck at the forefront of a highly competitive, multi-billion-dollar therapeutic class.
Dr. Eliav Barr, Chief Medical Officer of Merck Research Laboratories, emphasized the significance of the results:
“These positive Phase 3 induction results for tulisokibart are the first for an anti-TL1A biologic. They represent an important step forward for patients with moderately to severely active ulcerative colitis who – despite available treatments – continue to experience symptoms, and do not achieve clinical remission. These results reinforce the potential of this novel approach designed to help address immuno-fibrosis, a key driver of chronic immune dysregulation and disease progression in ulcerative colitis.” — Merck Press Release
Trial Design and Key Endpoints
The Phase 3 ATLAS-UC program (NCT06052059) consists of two independent studies: Study 1 (induction and maintenance) and Study 2 (induction-only). In Study 2, adult patients with moderately to severely active UC were randomized to receive either a high-dose IV of tulisokibart, a low-dose IV of tulisokibart, or an IV placebo.
The trial successfully met:
- Primary Endpoint: Clinical remission at Week 12 per the Modified Mayo Score (MMS).
- Key Secondary Endpoints: Endoscopic improvement, clinical response rate per MMS, and histologic-endoscopic mucosal improvement.
- Safety Profile: Consistent with previously reported Phase 2 studies, with no new safety concerns or signals identified.
The Mechanism of Immuno-Fibrosis
Tulisokibart is designed to target both the inflammatory and fibrotic pathways in the gut, a dual mechanism known as immuno-fibrosis. In chronic inflammatory bowel diseases (IBD) like UC, persistent inflammation activates fibroblasts, leading to deep transmural changes and progressive scarring (fibrosis) in the colorectal wall. By binding to both soluble and membrane-bound TL1A, tulisokibart aims to arrest this progressive tissue remodeling, offering a disease-modifying alternative to therapies that only address superficial mucosal inflammation.
Competitive Landscape and Commercial Stakes
Merck acquired tulisokibart through its $10.8 billion acquisition of Prometheus Biosciences in 2023. The positive Phase 3 readout provides the first late-stage clinical validation for the deal, which skeptics initially questioned due to its premium price tag.
The anti-TL1A class has become one of the most hotly contested areas in immunology, drawing massive big pharma investments:
- Roche entered the race by acquiring Telavant (and its TL1A candidate RVT-3101) from Roivant Sciences for $7.1 billion in late 2023.
- Sanofi partnered with Teva Pharmaceuticals in a $1.5 billion deal to co-develop another TL1A blocker, TEV-48574.
By delivering the first positive Phase 3 data, Merck secures a significant first-mover advantage. Beyond UC, Merck is actively developing tulisokibart across a broad "pipeline-in-a-product" strategy, with ongoing trials in seven indications including Crohn's disease (Phase 3 ARES-CD study), systemic sclerosis-associated interstitial lung disease (SSc-ILD), rheumatoid arthritis, psoriatic arthritis, radiographic axial spondyloarthritis, and hidradenitis suppurativa.
As Endpoints News noted:
"Merck’s tulisokibart hits Phase 3 primary endpoint in ulcerative colitis, a first win for anti-TL1A drugs and the $10.8B Prometheus deal." — Max Gelman, Endpoints News