Bruce Sands, MD 

Obefazimod As An “Exciting” Potential Treatment for Ulcerative Colitis, With Bruce Sands, MD

Despite an expanding treatment landscape, ulcerative colitis (UC) remains a challenging chronic condition for many patients, particularly those with moderate to severe disease who fail multiple lines of therapy. The need for new, effective, and better-tolerated options continues to drive innovation in the field.

American College of Gastroenterology (ACG)’s 2025 Annual Scientific Meeting

, attention turned to obefazimod, a first-in-class small molecule with a novel, non-immunosuppressive mechanism of action. Data from a pair of phase 3 studies, ABTECT 1 and ABTECT 2, were presented during a late-breaking session at ACG by Bruce Sands, MD, Chief of the Dr. Henry D. Janowitz Division of Gastroenterology at the Mount Sinai Medical Center and the Dr. Burrill B. Crohn Professor of Medicine at the Icahn School of Medicine at Mount Sinai, and shed further light on the treatment’s potential in UC.

“Obefazimob is a small molecule that promotes micro RNA 124, so it enhances micro RNA 124 expression, which then downregulates a number of pro-inflammatory signals within cells,” Sands explained to 

. “It is not immune suppressing, it actually just sort of regulates and normalizes the signals.”

ABTECT-1 and ABTECT-2 are global, multicenter, randomized, double-blind, placebo-controlled trials assessing once-daily oral administration of obefazimod at 25 mg or 50 mg doses in adult patients with moderately to severely active UC. Eligible participants had inadequate response, loss of response, or intolerance to conventional and/or advanced therapies.

The trials were conducted simultaneously and have enrolled patients from > 600 participating clinical trial sites in 36 countries with the intent to satisfy regulatory requirements globally. As described by parent company Abivax, the ABTECT program is one of the largest phase 3 UC trials ever conducted and includes the largest population of patients with inadequate response to JAK inhibitor therapy.

A total of 1272 patients were randomized and treated in ABTECT-1 (n = 636) and ABTECT-2 (n = 636). In both trials, baseline demographics and disease characteristics were similar between groups; 45.3% and 49.3% of patients had inadequate response to ≥ 1 advanced therapy.

In both trials, a significantly higher proportion of patients receiving obefazimod 50 mg achieved clinical remission and all key secondary endpoints versus placebo. In ABTECT-1, but not ABTECT-2, a significantly higher proportion of patients receiving obefazimod 25 mg achieved clinical remission and all key secondary endpoints. In a pooled analysis, both obefazimod 50 mg and 25 mg met all primary and secondary endpoints with nominal significance.

The rate of serious adverse events and treatment emergent adverse events (TEAEs) leading to study drug discontinuation for obefazimod-treated patients were similar to placebo. Investigators noted proportions of patients who reported ≥ 1 TEAE were greater for obefazimod 50 mg and similar for obefazimod 25 mg versus placebo in both trials, with headache being the most frequent TEAE.

“The exciting thing is that obefazimod is oral. It's once daily, so it's convenient. It's a small molecule, so it won't be immunogenic as some biologics can be, and this is an entirely new mechanism of action, so it's exciting to see that it may work in ulcerative colitis,” Sands said.

Editors’ Note: Sands reports relevant disclosures with AbbVie, Alimentiv, Amgen, Bristol Myers Squibb, AstraZeneca, Ferring, and others.

Sands BE, Danese S, Peyrin-Biroulet L, et al. Efficacy and Safety of Obefazimod in Patients With Moderately to Severely Active Ulcerative Colitis: Results From Two, Phase 3, Randomised, Double-Blind, Placebo-Controlled, 8-Week Induction Trials (ABTECT 1 & 2) (Late-Breaking Abstract). Presented at the American College of Gastroenterology (ACG)’s 2025 Annual Scientific Meeting. Phoenix, Arizona. October 27-29, 2025.

Brooks A. Obefazimod Meets Primary Endpoint in Phase 3 ABECT Program for Ulcerative Colitis. HCPLive. July 23, 2025. Accessed November 13, 2025. 

https://www.hcplive.com/view/obefazimod-meets-primary-endpoint-phase-3-abect-program-ulcerative-colitis

Videos

Sands explains the potential benefits of obefazimod and reviews findings from ABTECT 1 and ABTECT 2 presented at ACG 2025.

GALAXI Data and Guselkumab’s Role in Crohn’s Disease Care, with Bruce Sands, MD

Despite recent therapeutic advances, substantial unmet needs remain in moderate to severe 

, particularly for patients who are refractory to current biologics or require therapies with improved safety and durability. As the treatment landscape grows more complex—with anti-TNFs, integrin blockers, IL-12/23 inhibitors, JAK inhibitors, and now selective IL-23 blockers—clinicians continue to seek agents that offer reliable efficacy, durable remission, and broad applicability across patient populations.

New data from the GALAXI trial program evaluating guselkumab (Tremfya), a selective IL-23p19 inhibitor, are providing clinicians with critical insight into how this therapy may fit into evolving care paradigms.

“There are many unmet needs in IBD, especially in Crohn's disease,” senior author Bruce Sands, MD, Dr. Burrill B. Crohn Professor of Medicine at the Icahn School of Medicine at Mount Sinai, explained to 

, describing the different mechanisms of action of existing therapies and the potential benefits of newer IL-23 inhibitors like mirikizumab, risankizumab, and guselkumab.

Approved by the US Food and Drug Administration (FDA) for CD in March 2025, the decision marked guselkumab’s fourth indication in the US following initial approval from the FDA in 2017 for treatment of moderate-to-severe 

 and moderately to severely active ulcerative colitis in 2020 and 2024, respectively.

Findings from the phase 3 GALAXI 2 and 3 trials, described by Sands as being “gold standard trials,” provided the basis for the FDA approval of guselkumab for CD.

“This was really one of the most rigorously performed study programs ever, because it was double blinded, double dummy, but also included not only a placebo comparator, but an active comparator using an agent that we know to be effective in Crohn's disease, namely ustekinumab,” Sands explained. “We have comparison to placebo, comparison to an effective therapy, ustekinumab, all in a blinded fashion, and over 48 weeks. The other innovative thing is the treat through design, so what you see at the end is what you really started with at the beginning.”

The identically designed, 48-week, double-blind trials enrolled 1048 patients worldwide and randomly assigned them to 1 of 4 groups:

Guselkumab 200 mg intravenously (IV) at weeks 0/4/8, then guselkumab 100 mg subcutaneously (SC) every 8 weeks beginning at week 16

Guselkumab IV at weeks 0/4/8, then guselkumab 200 mg every 4 weeks beginning at week 12

Ustekinumab ~6 mg/kg IV at week 0, then ustekinumab 90 mg SC every 8 weeks beginning at week 8

In GALAXI-2, both guselkumab regimens were superior to placebo for the endpoint of clinical response at week 12 and clinical remission at week 48, which was observed in 55% of participants in the guselkumab 200 mg group, 49% of the guselkumab 100 mg group, and 12% of the placebo group. In GALAXI-3, the endpoint was observed in 48% of participants in the guselkumab 200 mg group, 47% of the guselkumab 100 mg group, and 13% of the placebo group.

Similarly, both guselkumab regimens were superior to placebo for the endpoint of clinical response at week 12 and endoscopic response at week 48 in GALAXI-2, observed in 38% of participants in the guselkumab 200 mg group, 39% of the guselkumab 100 mg group, and 5% of the placebo group. In GALAXI-3, the endpoint was observed in 36% of participants in the guselkumab 200 mg group, 34% of the guselkumab 100 mg group, and 6% of the placebo group.

“The efficacy is not just with regard to symptoms, but also with regard to endoscopic response, so we have both subjective and objective response and even remission,” Sands said. “We see it being effective in a range of patients who are naive to biologic therapies or advanced therapies, as well as patients who are refractory to other advanced therapies, so we can think of using it across the spectrum of disease.”

Of note, safety outcomes, based on adverse events and laboratory findings, were favorable and consistent with the known profile of guselkumab in approved indications.

“[Taken together, this] means we have a safe and effective therapy with convenient dosing regimens for patients with moderately, severely, moderately to severely Crohn's disease across the spectrum of disease,” Sands said.

Editors’ note: Sands has relevant disclosures with AbbVie, Alimentiv, Amgen, Bristol Myers Squibb, AstraZeneca, Ferring, and others.

Panaccione R, Feagan BG, Afzali A, et al. Efficacy and safety of intravenous induction and subcutaneous maintenance therapy with guselkumab for patients with Crohn's disease (GALAXI-2 and GALAXI-3): 48-week results from two phase 3, randomised, placebo and active comparator-controlled, double-blind, triple-dummy trials. 

Campbell P. FDA Approves Guselkumab (Tremfya) For Crohn Disease. 

. March 20, 2025. Accessed July 28, 2025. 

https://www.hcplive.com/view/fda-approves-guselkumab-tremfya-for-crohn-disease

Sands describes the current landscape of Crohn’s disease therapies and reviews GALAXI 2 and 3 data supporting guselkumab’s role in evolving care paradigms.

GALAXI Findings and Guselkumab’s Role in Crohn’s Disease Care, with Bruce Sands, MD

Measuring Patient Satisfaction with Inflammatory Bowel Disease Treatments and Communication Regarding Treatment Changes 

How do you evaluate patients’ satisfaction and expectations when providing care for UC and CD?

How do you discuss with patients the idea of escalating/switching therapy, perhaps in the absence of symptoms, and target something they may not feel?

Silvio Danese, MD, PhD; Bruce Sands, MD, and Jean-Frederic Colombel, MD, conclude by sharing their approaches to evaluating patient satisfaction and expectations when providing care for ulcerative colitis and Crohn's disease, while also touching upon the importance of discussing the potential need for escalating or switching therapies to better manage the underlying disease processes. 

Combination therapy in Inflammatory Bowel Disease

What is the current evidence on Advanced Combination Therapy for UC and CD? What are the benefits and challenges of this approach?

Medical experts in inflammatory bowel disease discuss the current evidence on dual advanced therapy for ulcerative colitis and Crohn's disease, highlighting the potential benefits, while also addressing the challenges and complexity of treatment management. 

Bruce Sands, MD

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