BARCELONA — The investigational oral drug obefazimod maintained clinical and endoscopic efficacy over 44 weeks in patients with moderate-to-severe ulcerative colitis (UC), including in those who had previously not responded to multiple advanced therapies, according to new findings from the ABTECT-Maintenance trial. 

“Treatment differences favored obefazimod over placebo across clinical, endoscopic, symptomatic, and histologic-endoscopic outcomes,” said Silvio Danese, MD, professor of gastroenterology at Vita-Salute San Raffaele University and IRCCS San Raffaele Scientific Institute, Milan, Italy, in presenting the data here at United European Gastroenterology (UEG) Week 2026.

Both the 25-mg and 50-mg doses were effective for each one of the endpoints, but it was always slightly better for the highest dose, he added.

The ABTECT Induction Trials 

Obefazimod is an investigational, once-daily oral small molecule that increases expression of microRNA-124, a regulator of inflammatory pathways involving Th17 cells and macrophages.

The randomized, double-blind, placebo-controlled ABTECT program initially enrolled 1272 patients with moderate-to-severe UC who had inadequate response, loss of response, or intolerance to at least one prior therapy (with no upper limit), including corticosteroids, immunosuppressants, biologics, S1P receptor modulators, and/or JAK inhibitors. Participants were randomly assigned in a 2:1:1 ratio to receive obefazimod 50 mg or 25 mg or placebo once daily for 8 weeks.

Previously reported results showed that patients with moderate-to-severe UC showed both clinically meaningful and quality-of-life improvements with obefazimod at 8 weeks. 

The ABTECT Maintenance Trial

A total of 580 patients who achieved a clinical response to obefazimod in the induction trials entered the 44-week maintenance trial. They were re-randomized to receive obefazimod 25 mg, obefazimod 50 mg, or placebo. 

Results announced by the company earlier this year showed the trial met the primary endpoint of clinical remission at 44 weeks (51.3% in the 50-mg obefazimod group, 50.8% in the 25-mg group, and 10.4% with placebo). And both doses met key secondary endpoints, including endoscopic improvement, endoscopic remission, and histologic endoscopic mucosal improvement.

For the current analysis, researchers separated the study participants by those who had prior advanced therapy inadequate response (prior AT-IR, defined as “inadequate response, loss of response or intolerance to advanced therapies including biologics, JAKs S1Ps with no upper limit”), and those who did not (AT-IR naive).

A total of 238 patients (41%) had prior AT-IR and 342 (59%) were AT-IR naive. Among AI-TR patients, clinical remission at week 44 of maintenance treatment (week 52 overall) was achieved by 34.2% receiving obefazimod 25 mg and 42.2% receiving 50 mg, compared with 6.9% receiving placebo. The placebo-adjusted treatment differences were 28.0 percentage points for the 25-mg dose and 33.1 percentage points for the 50-mg dose (both nominal P < .0001).

Among patients who were AT-IR naive, remission rates were higher overall and similar between doses: 61.5% with obefazimod 25 mg and 59.0% with 50 mg, compared with 12.5% with placebo (both nominal P < .0001).

Danese emphasized that the 50-mg dose produced numerically more favorable results in the prior-AT-IR group, adding, “I think this is consistent with the fact that these patients represent a more difficult-to-treat population.” 

Endoscopic Outcomes Reinforce Findings 

The numerical advantage of the higher dose in prior-AT-IR patients extended to endoscopic and histologic outcomes. In these patients, endoscopic improvement occurred in 38.2% receiving obefazimod 25 mg and 53.3% receiving 50 mg, compared with 8.3% receiving placebo (both nominal P < .0001).

More stringent endoscopic remission, defined as a Mayo endoscopic subscore of 0, was achieved by 23.7% and 38.9% of AT-IR patients receiving the respective doses, vs 5.6% with placebo (nominal P = .0049 and P < .0001, respectively). And histologic-endoscopic mucosal improvement was achieved by 34.2% of those receiving 25 mg and 48.9% of those receiving 50 mg, compared with 6.9% receiving placebo.

In contrast, among patients who were AT-IR naive, endoscopic remission rates were similar between doses, reaching 53.0% with 25 mg and 55.2% with 50 mg, compared with 12.5% with placebo.

“Both doses for each outcome are highly superior to placebo,” Danese pointed out.

Efficacy After Multiple Treatment Failures 

The investigators also examined whether efficacy was maintained among AT-IR patients who had not responded to several previous advanced therapies. Among patients with nonresponse to four or more advanced therapies, clinical remission occurred in 27.3% receiving obefazimod 25 mg and 33.3% receiving 50 mg, compared with none receiving placebo. Similarly, among patients with previous JAK inhibitor failure specifically, remission rates were 28.6% and 33.3%, respectively, compared with 0% with placebo.

These findings suggest that obefazimod may retain activity even after multiple treatment failures, although the small numbers in these subgroups limit the strength of the conclusions.

“Looking first at clinical remission, both obefazimod doses demonstrated efficacy regardless of the number of previous treatment lines,” Danese said. “Of course, the number of patients becomes progressively smaller as the number of previous treatment lines increases.”

Overall, the findings suggest that obefazimod can maintain efficacy in patients with previous advanced therapy failure, including those exposed to multiple treatment classes. However, the maintenance analysis included only patients who had already responded to obefazimod induction therapy.

Safety Findings 

Treatment-emergent adverse events were reported in 50.0% of placebo recipients, 58.0% receiving obefazimod 25 mg, and 71.8% receiving 50 mg. Adverse events leading to treatment discontinuation occurred in 6.8%, 2.6%, and 4.6% of patients, respectively. Serious treatment-emergent adverse events were uncommon, occurring in one placebo recipient and none receiving obefazimod.

Rates of serious or severe infections and opportunistic infections were low across treatment groups. Breast and prostate cancers were each reported in one patient receiving obefazimod 50 mg, alongside a small number of nonmelanoma skin cancers.

The overall safety findings were consistent with the previously reported profile, although treatment-emergent adverse events were more frequent with the 50-mg dose.

A Potential Option After Treatment Failure 

Commenting independently, co-moderator Peter Irving, MD, of Guy’s and St Thomas’ Hospital and King’s College London, UK, described the findings as encouraging, particularly the efficacy observed in previously treated patients.

“I think we saw what we often see, which is a slight drop-off in the biologic-exposed patients,” Irving told Medscape Medical News. “That kind of makes me believe the data even a bit more.”

He was particularly impressed by the stringent endoscopic remission findings. “When you look at the overall population, you look at the Mayo 0, it’s impressive,” he said.

The other session moderator, Virginia Solitano, MD, of IRCCS Ospedale San Raffaele, highlighted the potential clinical value of a treatment with a different mechanism of action. “We’re used to seeing therapies targeting cytokines or lymphocyte trafficking. This is different,” she told Medscape Medical News.

Solitano suggested that obefazimod could provide another option for patients who have not responded to existing treatments. “We need more options, especially for multidrug-resistant patients,” she said.

Danese reported relationships with AbbVie, Ferring, Hospira, Johnson & Johnson, Merck, MSD, Takeda, Mundipharma, Pfizer, Tigenix, UCB Pharma, Vifor, Biogen, Celgene, Allergan, Celltrion, Sandoz, and Boehringer Ingelheim. Irving reported other industry relationships but none relevant to this study. Solitano reported no relevant conflicts of interest. The study was sponsored by Abivax. 

Presented on October 20, 2026, at the United European Gastroenterology (UEG) Week 2026