2 days ago
Obefazimod Shows Long-Term Benefits in Ulcerative Colitis
Obefazimod 50 mg once daily demonstrated efficacy in patients with moderate to severely active ulcerative colitis (UC), with 52.5% achieved clinical remission at 96 weeks of open-label maintenance treatment with improvement in endoscopy scores and faecal calprotectin levels.
METHODOLOGY:
Obefazimod is an investigational oral small molecule that enhances the expression of a single micro-RNA regulating the inflammatory response. In a phase 2b, randomised placebo-controlled 8-week induction trial, obefazimod at three different doses achieved the primary endpoint in patients with moderate to severely active UC.
This 96-week open-label maintenance study was conducted including 217 patients (mean age, 42.1 years; 61.3% men) with moderate to severely active UC who were recruited at 69 study centres in 14 countries. All participants received 50 mg obefazimod once daily, regardless of their previous treatment and irrespective of their clinical response at the end of the induction trial.
After week 48, patients who showed clinical response, defined as a decrease in the modified Mayo score ≥ 2 points and ≥ 30% from baseline plus a decrease in the rectal bleeding subscore ≥ 1 or absolute rectal bleeding subscore ≤ 1, continued the treatment up to week 96.
Efficacy endpoints included rates of clinical remission, clinical response, endoscopic improvement, and endoscopic remission, along with the change in the stool frequency and faecal calprotectin levels from baseline of the maintenance study, assessed using non-responder imputation for missing data.
Safety measures comprised the incidence of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), discontinuations due to TEAEs, drug-related SAEs, and clinically significant laboratory abnormalities.
TAKEAWAY:
Of the 217 patients, 164 completed the study at week 96. By weeks 48 and 96, 81.6% and 72.8% of patients achieved a clinical response and 54.8% and 52.5% achieved clinical remission, respectively; endoscopic improvement was seen in 59.0% of patients and endoscopic remission seen in 35.9% at week 96.
Faecal calprotectin levels decreased from a median of 204.7 µg/g at baseline in the maintenance study to 89.6 µg/g at week 96, and 61.9% of patients achieved levels below 150 µg/g at week 96.
At both weeks 48 and 96, the proportion of patients who achieved the efficacy endpoints was numerically higher among those who showed a clinical response at week 8 than among those who did not. A proportion of patients also achieved corticosteroid-free endoscopic improvement and remission.
Overall, 68.2% of patients experienced at least one TEAE, with the most common being COVID-19 infection (14.3%) and headache (11.5%). TESAEs occurred in 8.3% of patients, and 7.8% discontinued because of TEAEs. No new safety signals or clinically meaningful changes in laboratory parameters were noted.
IN PRACTICE:
"[The study] findings suggest that long-term treatment with obefazimod provides continued improvement of clinical symptoms of the disease," the authors of the study wrote. "Although the central evaluation of endoscopy data reduced the risk of bias in this open-label study, the results must be interpreted with caution due to the absence of a control group," they added.
SOURCE:
This study was led by Severine Vermeire, University Hospitals Leuven, Leuven, Belgium. It was published online on May 26, 2025, in the Journal of Crohn's and Colitis .
LIMITATIONS:
Steroid cycling was not considered in the non-responder imputation method, which may have limited the interpretation of corticosteroid-free outcomes.
DISCLOSURES:
This study was supported by Abivax S.A. Seven authors reported being employees of Abivax. One author reported owning stocks in Abivax. Several authors reported receiving consultancy and/or speaking fees and grants and being consultants and advisory board members for various pharmaceutical companies.
