On February 22, 2025, Sanofi and Teva Pharmaceuticals presented detailed results from the Phase 2b RELIEVE UCCD clinical trial for their jointly developed inflammatory bowel disease (IBD) monoclonal antibody therapy, Duvakitug, at the 20th European Crohn’s and Colitis Organisation (ECCO) Congress. The trial data demonstrated that patients with ulcerative colitis (UC) and Crohn’s disease (CD) who received Duvakitug achieved remission by Week 14, highlighting its potential to become a “Best-in-Class” therapy. Both companies plan to initiate a Phase III clinical trial in the second half of 2025, advancing this innovative treatment toward clinical application.

The "Immortal" Cancer: Enhancing Clinical Remission Rates as a Key Strategy in IBD Treatment

UC and CD are the two primary forms of IBD, characterized by chronic gastrointestinal inflammation. Patients often experience symptoms such as abdominal pain, diarrhea, and rectal bleeding. Prolonged inflammation can lead to fibrosis, intestinal strictures, and obstructions, sometimes requiring surgical intervention. Studies have shown that Tumor Necrosis Factor-like Ligand 1A (TL1A) binds to its receptor DR3, amplifying immune responses and accelerating IBD-related fibrosis. Targeting TL1A can effectively suppress excessive immune activity, slow disease progression, and improve patient outcomes. Since IBD remains incurable, current treatment strategies focus on inducing remission, preventing relapse, and enhancing patient quality of life. Duvakitug, a human IgG1-λ2 monoclonal antibody targeting TL1A, has demonstrated promising efficacy in its Phase 2b clinical trial.

Comparison of Clinical Remission Rates of Duvakitug in UC Patients with and without Prior Advanced Therapy (Prior AT)²

As shown in the figure above, among UC patients, 36% of those in the 450 mg dose group achieved clinical remission (modified Mayo score, mMS), while the remission rate in the 900 mg dose group was 48%, significantly higher than the 20% in the placebo group. For patients with prior advanced therapy, the clinical remission rates in the 450 mg and 900 mg dose groups were 29% and 36%, respectively, much higher than the 7% in the placebo group. Among patients without prior advanced therapy, the remission rates in the 450 mg and 900 mg dose groups were 39% and 53%, higher than the 28% in the placebo group.¹

Clinical Response Rate, Endoscopic Improvement (MES), and Histologic-Endoscopic Mucosal Improvement (HEMI) of Duvakitug in the Treatment of UC Patients²

Meanwhile, in UC patients, both the 450 mg and 900 mg dose groups showed significant improvements in clinical response rate, endoscopic improvement (MES), and histologic-endoscopic mucosal improvement (HEMI). The clinical response rates were 81% and 70%, significantly higher than the 52% in the placebo group. The MES rates were 45% and 50%, compared to 23% in the placebo group. In terms of HEMI improvement, the two dose groups achieved 30% and 33%, surpassing 16% in the placebo group.¹

Comparison of Clinical Remission Rates of Duvakitug in CD Patients with and without Prior Advanced Therapy (Prior AT)²

In CD patients, Duvakitug also demonstrated significant efficacy. Overall, 26% of patients in the 450 mg dose group achieved clinical remission, while 48% in the 900 mg dose group achieved remission, significantly higher than the 13% in the placebo group. For patients with prior advanced therapy, the remission rates in the 450 mg and 900 mg dose groups were 11% and 48%, respectively, compared to only 4% in the placebo group. Among patients without prior advanced therapy, the remission rates in the 450 mg and 900 mg dose groups were both 47%, higher than the 23% in the placebo group.¹

Despite its "Best-in-Class" potential, the competition remains fierce

According to Evaluate Pharma, the global autoimmune disease drug market is expected to reach $140 billion by 2028, with the IBD drug market projected to reach $28 billion, capturing 20% of the market share. Currently, two anti-TL1A drugs are ahead of Duvakitug in clinical development: Merck's PRA023 and RVT-3101, jointly developed by Roivant and Pfizer.

• PRA023

PRA023 has demonstrated excellent efficacy in clinical trials for both UC and CD patients. In the Phase 2 clinical study ARTEMIS-UC, which focused on treating moderate to severe UC, the clinical remission rate in UC patients reached 26.5%, significantly higher than the 1.5% in the placebo group. Additionally, 36.8% of patients achieved the secondary endpoint of endoscopic improvement, compared to only 6% in the placebo group. Furthermore, the clinical response rate improved by nearly 44% (22.4% vs. 66.2%).

Phase 2 Clinical Trial Data of PRA023 for UC Patients - ARTEMIS-UC Study³

PRA023 has demonstrated excellent efficacy in clinical trials for both UC and CD patients. In the Phase 2 clinical study ARTEMIS-UC, which focused on treating moderate to severe UC, the clinical remission rate in UC patients reached 26.5%, significantly higher than the 1.5% in the placebo group. Additionally, 36.8% of patients achieved the secondary endpoint of endoscopic improvement, compared to only 6% in the placebo group. Furthermore, the clinical response rate improved by nearly 44% (22.4% vs. 66.2%).

Phase 2a Clinical Trial Data of PRA023 for CD Patients - APOLO-CD Study³

• RVT-3101

In the Phase 2 clinical trial for IBD, RVT-3101 achieved a clinical remission rate of 31% in UC patients, which increased to 40% in biomarker-positive patients, with an endoscopic remission rate as high as 56%.

Phase 2 Clinical Data of RVT-3101 for UC⁴

Compared to PRA023 and RVT-3101, Duvakitug demonstrated superior efficacy over placebo across multiple key clinical endpoints and showed consistent effects in patients with different treatment histories. These findings lay the groundwork for its Phase III clinical trial. However, there is still room for improvement in its development. Currently, Duvakitug requires dosing every two weeks, whereas both competitors have a more convenient four-week dosing schedule. To gain a competitive edge, accelerating Phase III trials and optimizing the dosing regimen to improve patient adherence will be crucial. Overall, the rise of TL1A-targeting therapies presents new opportunities for IBD treatment, driving advancements in the field. Ultimately, the biggest beneficiaries of this competition and innovation will be IBD patients.

Comprehensive TL1A-Targeted Drug Development Solutions

To meet the biologic drug development needs for IBD, ACROBiosystems has launched a series of high-quality tools that support applications from the molecular to the cellular level, including:

• Natural trimer-validated TL1A recombinant proteins, DR3 recombinant proteins and DcR3 recombinant protein: The natural trimer structure of TL1A protein has been verified by SEC-MALS. Both TL1A and DR3 proteins are expressed in human cells, covering multiple tags with features of high purity, high activity, and high batch-to-batch consistency. These are suitable for applications such as immunoassays, antibody screening, and candidate drug functional validation.

• Human DR3 (TL1A receptor) (Luc) Jurkat Reporter Cell Development Service: The product is validated through receptor expression and functional activity and can be applied in studies of TL1A agonist drug signaling pathways, cell-based drug activity assays and screening, as well as drug CMC quality control and release.

• HEK293/Human TL1A Stable Cell Line, HEK293/Membrane-Bound human TL1A Stable Cell Line, Raji/Membrane-Bound Human TL1A Stable Cell Line Development Service: The antigen is stably expressed on the surface of the host cell membrane over the long term, supporting applications such as antibody drug activity screening (cell-level binding and blocking) and CAR molecule cytotoxicity evaluation. Membrane-bound cell lines closely mimic the natural physiological interactions between TL1A and its receptors (e.g., DR3) on the cell membrane. They are ideal for studying membrane-bound signaling pathways and receptor interactions in drug development. These cell lines are suitable for anti-TL1A drug screening, receptor function research, signal transduction analysis, and high-throughput drug screening.

• TL1A [Biotinylated]: DR3 Inhibitor Screening ELISA Kit: Designed specifically for detecting and screening inhibitors of the TL1A-DR3 signaling pathway, this kit effectively quantifies the inhibitory effect of candidate molecules on the binding of TL1A to its receptor DR3. With high sensitivity and strong specificity, the kit is suitable for high-throughout screening in drug development, helping researchers quickly identify promising TL1A-targeted inhibitors and providing strong support for biologic therapies in diseases such as inflammatory bowel disease.

• Human TL1A-DR3 inhibition Kit (TR-FRET): Using Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) technology, this kit quantitatively detects the interaction between TL1A and DR3. With high sensitivity and low background interference, it is suitable for screening potential inhibitors of the TL1A-DR3 signaling pathway.

ACROBiosystems performs batch-by-batch quality control on all products, verifying properties such as purity and binding activity, and provides free protocols with experimental parameters and procedures developed by our research team to help you save R&D time.

References：

1. https://www.sanofi.com/en/media-room/press-releases/2025/2025-02-22-07-30-00-3030764

2. https://ir.tevapharm.com/Events-and-Presentations/events-and-presentations/event-details/2025/Teva-call/default.aspx

3. https://www.sec.gov/Archives/edgar/data/1718852/000119312522299773/d420864dex991.htm

4. https://delta.larvol.com/NewsItem/Default.aspx?NewsItemID=220ba66f-7e9a-4955-a0ae-03c63c34529a&ts=638763024105251773