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 approximately 3 million cases in 2023 and are projected to increase by 2034. As per the estimates, in 2023 approximately 60% of cases accounted for the moderate to severe cases of ulcerative colitis among the 7MM.

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 treatment options greatly affects patients’ quality of life and everyday functioning. Although current treatments 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 solutions to tackle these challenges.

Several FDA-approved drugs for treating ulcerative colitis are SIMPONI (Janssen Pharmaceuticals), ENTYVIO (Takeda Pharmaceuticals), Etrasimod (Arena Pharmaceuticals/Pfizer), 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 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.

Recently, 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 treatment is highly competitive, with numerous companies such as Arena Pharmaceuticals, Pfizer, Abivax, Reistone Biopharma, InDex Pharmaceuticals, AbbVie, Boehringer Ingelheim, Janssen Pharmaceuticals, Landos Biopharma, NImmune, Merck, Mesoblast, and others conducting clinical trials to advance treatment options. Promising ulcerative colitis drugs in mid-stage development are expected to enter the market soon, enhancing the ulcerative colitis treatment landscape.

Now, let’s examine the top 7 pipeline therapies under investigation for ulcerative colitis

Risankizumab: AbbVie and Boehringer Ingelheim

Registered

Risankizumab (ABBV-066) is an anti-IL-23 antibody under investigation for treating several inflammatory diseases, such as psoriasis, Crohn’s disease (CD), ulcerative colitis, and psoriatic arthritis. This humanized monoclonal antibody works by targeting the p19 component of IL-23, thereby preventing IL-23 from binding to its receptor (IL-23R) and blocking the activation of the pro-inflammatory JAK/STAT signaling pathway. IL-23, a cytokine involved in inflammatory responses, is believed to be linked to various chronic immune-mediated diseases.

TREMFYA (guselkumab): Janssen Pharmaceuticals

Phase III

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.

In May 2024, Johnson & Johnson revealed that the Phase III QUASAR maintenance study in ulcerative colitis met its primary endpoint and all major secondary endpoints, including significant rates of endoscopic remission. Consequently, the company has submitted a supplemental Biologics License Application (sBLA) to the FDA based on these findings.

ABX464 (Obefazimod): Abivax

Phase III

Obefazimod, an oral small-molecule drug candidate, is currently undergoing clinical development for treating moderately to severely active ulcerative colitis. It has shown anti-inflammatory effects in preclinical studies and in Phase IIa and Phase IIb clinical trials. Abivax completed a randomized, double-blind, placebo-controlled Phase IIb trial in April 2021 across 15 European countries, the United States, and Canada, involving 252 patients. The trial successfully achieved its primary endpoint, demonstrating a statistically significant reduction in Modified Mayo Score after eight weeks of once-daily administration of obefazimod (25 mg, 50 mg, 100 mg).

In September 2023, the company presented an interim evaluation of reducing the dose from 50 mg to 25 mg during the third and fifth years of continuous open-label maintenance therapy with obefazimod in patients with ulcerative colitis. Previously, these patients had received 50 mg of oral obefazimod once daily for approximately four years in a Phase IIa clinical trial and around two years in a Phase IIb clinical trial. Eligible patients, who initially had a Mayo endoscopic subscore of 0 or 1, were switched to a 25 mg dose, and an interim analysis was conducted at week 48, with data collected up to July 31, 2023. Of the 71 eligible patients, 63 completed their 48-week visit. Among these patients, 53 out of 63 (84%) demonstrated disease control (maintained or improved Modified Mayo Score). No new safety concerns were identified in ulcerative colitis patients treated for up to five years with oral obefazimod administered once daily.

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.

Tulisokibart (MK-7240)/PRA023: Merck

Phase III

Tulisokibart is a new type of antibody designed for targeting TNF-like ligand 1A (TL1A), currently under investigation. It became part of Merck’s portfolio through the acquisition of Prometheus Biosciences, Inc. in June 2023. In December 2022, Prometheus reported positive outcomes from the ARTEMIS-UC study, a Phase II trial that assessed the safety and effectiveness of MK-7240 in patients with moderate-to-severe ulcerative colitis, and the APOLLO-CD study, a Phase IIA trial that evaluated its performance in patients with moderate-to-severe Crohn’s disease. These findings were recently presented at the 18th Congress of the European Crohn’s and Colitis Organisation (ECCO).

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 emerging therapies for ulcerative colitis treatment 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 therapies, there is newfound hope. These treatments 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 therapies 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 therapies, clinicians can optimize outcomes and minimize adverse effects. The availability of diverse treatment options 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 emerging therapies 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.