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.

At the 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 HCPLive. “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.

References

1. 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.

2. 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