Duvakitug Week 44 Durability Impresses but Uncontrolled LTE Leaves Phase 3 Proof Pending

Duvakitug Demonstrates Sustained Efficacy in Ulcerative Colitis and Crohn's Disease

Sanofi and Teva announced positive long-term extension (LTE) data from the Phase 2b RELIEVE UCCD study for duvakitug in moderately-to-severely active ulcerative colitis (UC) and Crohn’s disease (CD). Presented at UEG Week 2026, the data showed duvakitug maintained high rates of clinical remission, clinical response, and endoscopic improvement in UC patients at Week 44, with 58% achieving clinical remission at the 900 mg dose. In CD patients, high rates of endoscopic response (55% at 900 mg), clinical response, and clinical remission were maintained at Week 44. The investigational TL1A inhibitor was well tolerated, with a safety profile consistent with the induction study.

• At Week 44 of the maintenance phase, duvakitug demonstrated high rates of clinical remission (up to 58% at 900 mg Q4W), clinical response (up to 87% at 900 mg Q4W), and endoscopic improvement (up to 63% at 900 mg Q4W) in UC patients. These outcomes, measured by the modified Mayo Score and Mayo Endoscopic Score, showed a dose-response, with numerically higher efficacy at the 900 mg dose.
• For CD patients, duvakitug maintained high rates of endoscopic response (up to 55% at 900 mg Q4W), clinical response (up to 87% at 900 mg Q4W), and clinical remission (up to 84% at 900 mg Q4W) at Week 44. Efficacy was assessed using the Simple Endoscopic Score for Crohn’s Disease (SES-CD) and Crohn’s Disease Activity Index (CDAI), also indicating a dose-response.
• Duvakitug was generally well tolerated throughout the 44-week maintenance period, with a safety profile consistent with the induction phase and no new safety concerns. Biomarker analyses from the induction study further revealed that duvakitug reduced markers of inflammation and tissue remodeling, providing mechanistic evidence for TL1A inhibition's potential role in addressing both inflammation and fibrosis in IBD.
• Following these positive Phase 2b results, duvakitug is progressing into multiple Phase 3 studies for moderately-to-severely active UC (SUNSCAPE-1, SUNSCAPE-2) and CD (STARSCAPE-1, STARSCAPE-2). Additionally, Sanofi and Teva have initiated a Phase 2 study in hidradenitis suppurativa (AURALIGHT) and are planning another for fibrostenotic Crohn’s disease, expanding the drug's potential therapeutic scope.

Addressing Persistent Inflammation in Ulcerative Colitis and Crohn's Disease

Recent literature centers on moderate-to-severe ulcerative colitis (UC) that remains active despite corticosteroids and prior biologics, with emphasis on achieving durable steroid-free and endoscopic remission while improving safety and persistence. Studies evaluate advanced therapies in biologic-naïve, biologic-experienced, and multi-refractory populations, including acute severe and rescue settings, alongside biomarker and drug-monitoring strategies to personalize treatment.

• Multi-refractory moderate-to-severe UC with prior biologic failure: A retrospective multicentric study included 75 UC patients with 96% prior anti-TNF and 97% antiintegrin exposure, with 56% on concomitant steroids, where clinical remission was achieved by 43% at the end of follow-up, endoscopic response and remission were observed in 37% and 9%, and 34 patients (45%) discontinued tofacitinib, primarily due to primary non-response (62%). Upadacitinib was evaluated in 236 IBD patients including 80 UC patients, where at 8 weeks 64.0% achieved steroid-free remission, 57.6% clinical remission, and 81.8% response, with endoscopic remission of 35.8% (p = 0.039), 63.3% response and 35.8% mucosal healing, and histological remission of 29.2% (p = 0.009), described as particularly in biologic-resistant cases.

• Corticosteroid-refractory, corticosteroid-dependent, and acute severe UC requiring rescue and colectomy avoidance: A prospective longitudinal study included 23 corticosteroid-refractory or -dependent UC patients who started Adalimumab after endoscopy-confirmed flare-ups, where sixty percent of patients achieved clinical remission. In 92 UC patients receiving IV cyclosporin for severe, steroid-refractory UC, clinical response was achieved in 88.0% and clinical remission was observed in 23.9%, with probability of colectomy-free survival of 74.7%, 62.6%, 57.1%, and 45.6% at 1, 3, 5, and 14 years. In 107 patients who showed clinical response at day 30 after first systemic corticosteroids, 33 (30.8%) developed steroid dependency, defined as clinical relapse during tapering or within 3 months after completion of corticosteroids.

• Anti-TNF response variability, loss of response, immunogenicity, and need for predictive monitoring: In a Danish multicenter cohort of 774 patients (706 infliximab, 68 adalimumab) followed for a median duration of 125 weeks, clinical response was achieved in 209/331 (67.4%) of UC patients, while 143/331 (46.1%) UC patients achieved clinical remission, and in 294 UC patients who received maintenance therapy, 86/294 (29.3%) UC patients experienced LOR. Responders had significantly higher serum trough concentrations than non-responders for infliximab [3.75 µg/mL (IQR: 3.40-4.15) vs. 1.05 µg/mL (IQR: 0.92-1.12)] and adalimumab [6.32 µg/mL (IQR: 5.67-7.15) vs. 3.30 µg/mL (IQR: 2.70-4.26)], with adalimumab-treated non-responders having significantly higher ADAb levels compared with responders. In UC, responders (Mayo score 0-1) versus non-responders (Mayo score ≥ 2) showed divergent stool and mucosal changes, with stool microbiota showing increased Bacteroidetes and decreased Proteobacteria abundances with enrichment of Faecalibacterium prausnitzii, Bifidobacterium, and Akkermansia muciniphila in responders.

• Deeper healing targets beyond symptoms and comparative persistence and safety of advanced therapies: Mucosal healing was observed in 18 out of 30 patients (60.0%) with filgotinib, in 57.9% of 192 UC patients on thiopurine monotherapy after a median of 18 months, and endoscopic remission with histological remission was reported at week 52 in cyclosporin and ustekinumab combination therapy for steroid-refractory acute severe UC. First-line drug survival in UC was 0.60 (0.52-0.67) vs 0.76 (0.67-0.84) at year 1 and 0.37 (0.30-0.44) vs 0.50 (0.36-0.64) at year 4 for anti-TNF agents vs vedolizumab, with PRO-2 remission of 94.8 vs 78.9% (P = 0.002). In 9,430 UC patients followed over median 27 months, anti-interleukins were associated with lower risk of serious infections compared with TNF antagonists [HR,0.66 (95%CI, 0.51-0.87)] and anti-integrins [HR,0.75 (0.57-0.98)], and JAK inhibitors were associated with lower risk compared with TNF antagonists [HR,0.66 (0.46-0.94)], with incidence of VTE 1.4-2.0 per 100py and MACE 0.5-1.0 per 100py without significant differences across agents.

Duvakitug's Sustained Efficacy and Safety in RELIEVE UCCD LTE

Recent ulcerative colitis studies evaluate oral small molecules, biologics and mesalazine-based regimens across induction and long-term maintenance, with endpoints including clinical remission, endoscopic improvement and mucosal healing. Safety reporting focuses on infection events and treatment-emergent adverse events, with no new safety signals described in longer-term follow-up.

Unpacking TL1A Inhibition: Biomarker Insights from Duvakitug Studies

Duvakitug has been studied as one of the TL1A-neutralizing antibodies, alongside afimkibart and tulisokibart, in moderate-to-severe IBD. These trials have demonstrated encouraging efficacy and safety in moderate-to-severe IBD, positioning TL1A blockade as a promising dual-pathway therapeutic approach targeting inflammation and fibrotic remodeling.

Biomarker work around this class is described as emerging biomarker strategies suggesting potential for personalized treatment. Supporting biology includes genetic variants in TNFSF15, which encodes TL1A, linking increased TL1A expression with susceptibility to Crohn's disease, ulcerative colitis, and fibrostenotic complications. A similar TAN-like gene signature was enriched in human colitis-associated dysplasia but reduced following TL1A blockade in ulcerative colitis patients.

Duvakitug's Expanding Clinical Program Beyond UC and CD

Duvakitug is one of three anti-TL1A monoclonal antibodies (tulisokibart, afimkibart, and duvakitug) that have advanced to phase 3 trials across multiple global programs. Beyond ulcerative colitis, its development is centered in Crohn's disease, reflecting TL1A-DR3 positioning as a central driver of both chronic inflammation and fibrosis.

• Crohn's disease is the additional IBD indication for duvakitug, with endoscopic response rates of 26%-48% in Crohn's disease reported from phase 2 trials.

• Early-phase moderate-severe IBD trials (e.g., tulisokibart, duvakitug) show clinical/endoscopic remission, with phase 3 programs ongoing.

• In Crohn's disease, duvakitug is grouped with emerging anti-fibrotic strategies alongside an ALK5 inhibitor (AGMB-129) and targeted AGR2 therapies (TH-009), consistent with TL1A directly activating intestinal fibroblasts and contributing to extracellular matrix deposition. The knowledge base does not have sufficient information on this aspect.

Duvakitug's Long-Term Data Bolsters TL1A's Promise in IBD

The recent long-term extension data from the Phase 2b RELIEVE UCCD study for duvakitug marks a significant moment for inflammatory bowel disease (IBD) therapeutics. Sanofi and Teva's investigational TL1A inhibitor demonstrated sustained high rates of clinical remission, clinical response, and endoscopic improvement in both ulcerative colitis (UC) and Crohn's disease (CD) patients at Week 44, alongside a well-tolerated safety profile. This robust data reinforces the promise of TL1A inhibition as a novel therapeutic strategy.

The TL1A-DR3 signaling pathway is increasingly recognized as a central driver of both chronic inflammation and fibrotic remodeling in IBD. By targeting this pathway, duvakitug offers a dual anti-inflammatory and anti-fibrotic mechanism, addressing a critical unmet need for patients who experience inadequate response to existing therapies or develop irreversible complications like strictures. This positions duvakitug as a potential cornerstone therapy, particularly for patients with more complicated disease phenotypes.

However, the landscape for TL1A inhibitors is rapidly evolving and becoming highly competitive. The pipeline includes numerous other anti-TL1A antibodies, bispecifics, and DR3 antagonists, all vying for market share. While the positive data for duvakitug validates the mechanism, it also highlights the need for clear differentiation. Furthermore, while companion diagnostics for TNFSF15 risk variants are being explored to identify potential responders, their definitive utility in patient stratification still requires robust validation in Phase 3 trials. The long-term safety profile, beyond the mild adverse events observed in early studies, will also be a critical factor as the drug progresses. Ultimately, duvakitug's continued success will depend on its ability to demonstrate superior or differentiated long-term outcomes and a clear patient selection strategy within this burgeoning therapeutic class.