Top 7 Breakthrough Drugs for Ulcerative Colitis Treatment

Ulcerative colitis is a type of inflammatory bowel disease of unknown origin that targets the lining of the colon. Symptoms typically include diarrhea, abdominal pain, discomfort, and the presence of blood in the stool. The severity of the condition can vary, with inflammation affecting just the rectum, extending to the splenic flexure on the left side of the colon, or involving the entire rectum and colon.

As per DelveInsight analysis, the total ulcerative colitis diagnosed prevalent cases in the 7MM comprised 3.2 million cases in 2024 and are projected to increase by 2034. As per the estimates, in 2024, approximately 60% of cases accounted for the moderate to severe cases of ulcerative colitis among the 7MM.

The treatment options for ulcerative colitis vary based on the disease’s severity and can be categorized into six main types: conventional therapies, biologics, S1P-receptor modulators, and JAK inhibitors. New mechanisms of action, such as LANCL2 protein stimulators, miR-124 enhancers, TNF-like ligand 1A inhibitors, and toll-like receptor 9 agonists, among others, are expected to broaden the range of ulcerative colitis medications.

Over the years, there have been substantial improvements in the treatment of ulcerative colitis. Despite this, safety continues to be a significant concern. The absence of safer and curative UC meds greatly affects patients’ quality of life and everyday functioning. Although current colitis drugs benefit some individuals with ulcerative colitis and Crohn’s disease, many require multiple lines of therapy, highlighting the need for alternative treatments to manage the disease effectively. Several major pharmaceutical companies are working together to develop new drug for colitis to tackle these challenges.

Several FDA-approved drugs for ulcerative colitis are SIMPONI (Janssen Pharmaceuticals), ENTYVIO (Takeda Pharmaceuticals), XELJANZ/XELJANZ XR (Pfizer), STELARA (Janssen Pharmaceuticals), CAROGRA (EA Pharma/Kissei Pharma), JYSELECA (Gilead Sciences and Galapagos NV), RINVOQ (AbbVie), ZEPOSIA (Bristol-Myers Squibb), REMICADE (Janssen Pharmaceuticals), HUMIRA (AbbVie), OMVOH (Eli Lilly), and SKYRIZI (AbbVie).

SIMPONI is a human monoclonal antibody designed to target and neutralize excess tumor necrosis factor (TNF)-alpha, a protein linked to inflammation and tissue damage in chronic inflammatory diseases. It is the first subcutaneous anti-TNF-alpha treatment administered every four weeks as maintenance therapy for ulcerative colitis. Approved for treating moderately to severely active ulcerative colitis in adults, SIMPONI is also being tested in ongoing trials for pediatric patients with the same condition.

Vedolizumab is a humanized monoclonal antibody that targets and blocks the alpha 4 beta 7 integrin, preventing it from binding to the intestinal mucosal addressin cell adhesion molecule 1 (MAdCAM-1). This integrin is present in a specific group of circulating white blood cells involved in the inflammatory processes of ulcerative colitis and Crohn’s disease. By inhibiting the alpha 4 beta 7 integrin, vedolizumab may decrease the infiltration of these white blood cells into gut tissues.

It is presently approved for managing moderate to severe ulcerative colitis in adults who have not shown improvement with, have ceased responding to, or cannot tolerate traditional therapy or a tumor necrosis factor-alpha (TNFα) blocker.

Etrasimod (APD334) is a novel oral UC medication taken once daily, designed to selectively modulate the sphingosine 1-phosphate (S1P) receptor. Developed by Arena Pharmaceuticals, it is engineered to interact optimally with S1P receptors 1, 4, and 5, potentially offering improved effectiveness and safety. Etrasimod targets specific immune cells both throughout the body and locally, presenting a promising treatment option for various immune-mediated inflammatory conditions like Crohn’s disease and ulcerative colitis.

Currently approved by the FDA and EMA, Etrasimod is indicated for adults with moderately to severely active ulcerative colitis who have had inadequate responses to, lost response to, or could not tolerate conventional or advanced therapies.

On June 18, 2024, the FDA approved SKYRIZI for the treatment of adult patients with moderately to severely active ulcerative colitis. This milestone expands the drug’s accessibility to approximately 1 million patients in the United States. SKYRIZI becomes the first IL-23 inhibitor approved for both ulcerative colitis and Crohn’s disease, the two main types of inflammatory bowel disease (IBD).

Following a 12-week induction period, patients can administer the medication at home using an on-body injector device, which AbbVie’s press release describes as user-friendly. This device adheres to the body and delivers the medication in approximately five minutes.

Since its initial approval for Crohn’s disease in 2022, SKYRIZI has emerged as a formidable competitor to Johnson & Johnson’s popular drug STELARA in the IBD market. AbbVie’s medication has captured a significant portion of STELARA’s market share.

The market for ulcerative colitis drugs is highly competitive, with numerous companies such as Janssen Pharmaceuticals, Roche, Eli Lilly, Abivax, Landos Biopharma, NImmune, Merck, Takeda, Mesoblast Ltd., and others conducting clinical trials to advance treatment options. Promising ulcerative colitis drugs in various stages of development are expected to enter the market soon, enhancing the ulcerative colitis treatment landscape.

Now, let’s examine the 7 best medications for ulcerative colitis under investigation

TREMFYA (guselkumab): Janssen Pharmaceuticals

Registration

TREMFYA (guselkumab) is a human monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, developed by Janssen. IL-23 plays a key role in the development of inflammatory diseases like ulcerative colitis and Crohn’s disease. As an interleukin-23 inhibitor, TREMFYA is a human immunoglobulin G1 lambda (IgG1λ) monoclonal antibody produced in a mammalian cell line through recombinant DNA technology. It specifically binds to the p19 subunit of IL-23, preventing its interaction with the IL-23 receptor.

Recently, in May 2025, Johnson & Johnson revealed new findings from the Phase III QUASAR long-term extension (LTE) study of TREMFYA in adults with moderately-to-severely active ulcerative colitis (UC). These findings are part of 24 abstracts showcasing the company’s research at Digestive Disease Week (DDW) 2025. The QUASAR LTE study data show that patients treated with TREMFYA maintained both clinical and endoscopic effectiveness at Week 92:

• 72% of patients were in clinical remission, with 99% of them remaining corticosteroid-free for 8 weeks or more through Week 92.
• 43% of patients achieved endoscopic remission.
• Among patients who showed endoscopic improvement at Week 44, 84% maintained this improvement through Week 92.

Patients treated with TREMFYA consistently sustained clinical and endoscopic remission, regardless of their prior biologic or JAK inhibitor treatment history.

ABX464 (Obefazimod): Abivax

Phase III

ABX464 is a first-in-class, orally administered small molecule that selectively increases the expression of miR-124 in immune cells. This molecule has shown a strong safety profile and significant anti-inflammatory effects across preclinical studies and Phase IIa and IIb induction trials for ulcerative colitis. ABX464’s mechanism of action, marked by the substantial upregulation of miR-124, a novel RNA splicing product with anti-inflammatory properties, sets it apart from other treatments. Clinical trials have indicated its potential to induce remission and heal inflammatory lesions in ulcerative colitis patients.

The pivotal Phase III ABTECT program is underway, with the first patient in the U.S. enrolled in October 2022. Final patient enrollment for the induction trials is expected in early Q1 2025. Top-line results from the 8-week induction study are anticipated in early Q2 2025, followed by data from the 44-week maintenance trial in Q1 2026. A New Drug Application (NDA) submission is targeted for the latter half of the first half of 2026.

BT-11 (Omilancor): Landos Biopharma/NImmune 

Phase III

Omilancor is an innovative, gut-restricted therapeutic in Phase III readiness, intended to overcome the drawbacks of existing treatments for ulcerative colitis and Crohn’s disease. It offers once-daily oral dosing, minimal systemic exposure, and enhanced tolerability without significant toxicity concerns.

Omilancor operates by targeting LANCL2, a membrane receptor that regulates immunological processes linked to ulcerative colitis and Crohn’s disease. This targeting stimulates the production of regulatory CD4+ cells (Tregs), which act locally at the inflammation site in the gastrointestinal tract. This mechanism aims to restore and sustain immune tolerance.

At Digestive Disease Week 2025, new clinical research highlighted the effectiveness of daily oral omilancor in achieving clinical remission in 30.4% of patients with active ulcerative colitis (UC) and 33.3% of those with biologic-refractory UC at the Phase 3 dose of 440 mg/day. The latest findings also revealed that omilancor reverses immunometabolic dysfunction in patients with severe ulcerative colitis and triggers clinical remission, with biomarker improvements observable within just two weeks of starting treatment. Across multiple clinical trials, omilancor has consistently demonstrated an excellent safety profile, with no treatment-related adverse events reported. 

This new colitis medication was shown to restore depleted colonic regulatory T cells (Tregs) and correct mitochondrial dysfunction, hallmarks of a difficult-to-treat UC patient subgroup that appears particularly responsive to LANCL2-targeting therapies. These results support omilancor’s path toward commercialization for ulcerative colitis, reinforce plans to finalize its Phase III program, and aim for a New Drug Application (NDA) submission to the US FDA by 2027, with further NDA filings to follow.

Tulisokibart (MK-7240)/PRA023: Merck

Phase III

Tulisokibart is an experimental humanized monoclonal antibody targeting the tumor necrosis factor (TNF)-like ligand 1A (TL1A). It became part of the pipeline through the acquisition of Prometheus Biosciences. This ulcerative colitis drug is currently in Phase III clinical trials. In a Phase II study (NCT04996797), tulisokibart showed greater effectiveness than placebo in achieving clinical remission in patients with moderately to severely active ulcerative colitis.

MORF-057: Eli Lilly

Phase II

MORF-057 is an oral, selective small molecule inhibitor targeting the α4β7 integrin, developed for treating inflammatory bowel disease (IBD). The α4β7 integrin is a validated therapeutic target in IBD, as demonstrated by the clinical success of vedolizumab, an approved injectable antibody. Similar to vedolizumab, MORF-057 aims to disrupt the interaction between α4β7 on lymphocytes and the mucosal addressin cell adhesion molecule-1 (MAdCAM-1) on endothelial cells. This mechanism reduces the migration of lymphocytes into the intestinal mucosa, thereby limiting inflammation linked to IBD.

In August 2024, Eli Lilly and Company announced it had completed the acquisition of Morphic Holding, Inc., which includes MORF-057 in its portfolio. Eli Lilly is currently evaluating this ulcerative colitis drug in the phase II stage of development. 

TAK-279: Takeda

Phase II

TAK-279, currently in the advanced stages of development, is a specialized oral inhibitor targeting allosteric tyrosine kinase 2 (TYK2). It demonstrates exceptional selectivity, showing approximately 1.3 million times greater affinity for TYK2 compared to JAK1. TAK-279 holds promise as a significant therapeutic option for various immune-mediated inflammatory conditions.

Remestemcel-L: Mesoblast Ltd.

Phase I/II

Remestemcel-L, developed by Mesoblast Ltd., contains 100 million mesenchymal stem cells (MSCs). In preclinical studies, it has shown immunomodulatory abilities by regulating T-cell mediated inflammatory responses, inhibiting T-cell proliferation, and reducing the production of pro-inflammatory cytokines like TNF-alpha and interferon-gamma. Importantly, MSCs can effectively down-regulate Th17 cells, lower IL-17 levels, and induce FOXP3 regulatory T cells. These inflammatory pathways are key to the pathogenesis of inflammatory conditions. Remestemcel-L is currently in Phase I/II of clinical development.

The anticipated launch of these new drugs for ulcerative colitis represents a significant advancement in the treatment landscape, promising profound impacts on patient outcomes and quality of life. Traditionally, managing ulcerative colitis has been challenging, with many patients experiencing recurrent symptoms and potential complications. However, with the introduction of these novel medicines for ulcerative colitis, there is newfound hope. These ulcerative colitis meds often target specific pathways involved in the inflammatory process, offering the potential for more effective symptom control and disease management. This not only reduces the frequency and severity of flare-ups but also aims to achieve long-term remission, which is crucial for improving the overall well-being of patients.

Moreover, the advent of these medicines for ulcerative colitis marks a shift towards personalized medicine in gastroenterology. By tailoring treatment strategies based on individual patient profiles, including disease severity, genetic factors, and response to previous meds for colitis, clinicians can optimize outcomes and minimize adverse effects. The availability of diverse drugs for colitis also empowers healthcare providers to better address the varying needs of patients, potentially reducing healthcare costs associated with disease complications and hospitalizations. Overall, the launch of new drugs for ulcerative colitis treatment signifies a transformative era in gastrointestinal care, promising better control of symptoms, enhanced patient adherence, and improved overall quality of life for those affected by this chronic inflammatory condition.