Obefazimod hits targets in identical trials on active UC

Two phase III induction trials have demonstrated the efficacy and safety of obefazimod, an oral, first-in-class, small molecule, for the treatment of adults with moderate-to-severe ulcerative colitis (UC).

“In both ABTECT induction trials, the primary and secondary endpoints were met,” noted the investigators at AIBD 2025. “Obefazimod treatment led to statistically significant improvements in clinical, endoscopic, symptomatic, and combined endoscopic-histologic endpoints at week 8.”

The primary endpoint was clinical remission (per modified Mayo score), while the secondary endpoints included clinical response, endoscopic improvement, symptomatic remission, and histo-endoscopic mucosal improvement.

A total of 1,272 participants were enrolled across the ABTECT-1 (n=636) and ABTECT-2 (n=636) trials. The participants were randomized 2:1:1 to receive obefazimod 50 mg QD, obefazimod 25 mg QD, or placebo for 8 weeks. Approximately 50 percent of the participants had inadequate response to ≥1 advanced therapy. [AIBD 2025, abstract 130]

In ABTECT-1, the proportion of participants who achieved clinical remission was significantly higher in the obefazimod 50-mg arm than the placebo arm (21.7 percent vs 2.5 percent; difference, 19.3 percent; p<0.0001). A similar pattern was observed in ABTECT-2 (19.8 percent vs 6.3 percent; difference, 13.4 percent; p=0.0001).

There were also more patients treated with obefazimod 50 mg who achieved endoscopic remission compared with placebo, both in ABTECT-1 (17.9 percent vs 4.4 percent; difference, 13.6 percent; p<0.0001) and ABTECT-2 (18.9 percent vs 5.7 percent; difference, 13.2 percent; p=0.0001).

The lower obefazimod dose also fared better than placebo in terms of clinical remission (difference, 21.4 percent; p<0.0001) and endoscopic remission (difference, 23.1 percent; p<0.0001) in ABTECT-1.

“In a pooled analysis, both obefazimod [doses] met all primary and secondary endpoints with nominal significance (p=0.0001),” the investigators noted.

Safety profile

The overall rates of serious adverse events (AEs) and treatment-emergent AEs (TEAEs) leading to drug discontinuation were similar between obefazimod and placebo, the investigators said.

In ABTECT-1, the proportions of participants who reported at least one TEAE were 59.4, 46.9, and 53.2 percent with obefazimod 50 mg, obefazimod 25 mg, and placebo, respectively. The corresponding rates in ABTECT-2 were 61, 50.9, and 48.4 percent, respectively.

Headache was the most frequent TEAE, with approximately a quarter of participants on the higher obefazimod dose reporting events. With the lower obefazimod dose, 16 percent reported headaches. However, these were mild, transient, short, and did not affect treatment, as evidenced by a low discontinuation rate (<1 percent).

There were no signals for serious, severe, or opportunistic infections or malignancies.

New therapies warranted

“There is an urgent need for new therapies to treat UC that deliver durable efficacy, safety, and the simplicity of oral, once-daily dosing,” noted study investigator Dr Bruce Sands from the Icahn School of Medicine at Mount Sinai, New York City, New York, US, in a press release.

“The ABTECT trials enrolled individuals with advanced disease, including many who had failed multiple lines of advanced therapy and a significant percentage of patients with prior Janus kinase inhibitor failure. The refractory nature of this population underscores the significance of the results,” said Sands.