Treatment with obefazimod (ABX464) at 3 different doses was more effective than placebo for improving the modified Mayo score (MMS) at week 8 in patients with moderate to severe, active ulcerative colitis (UC) and for those who had not responded to second-line therapy, according to a study in The Lancet Gastroenterology & Hepatology.
The phase 2b, double-blind, randomized, placebo-controlled induction trial (ClinicalTrials.gov Identifier: NCT04023396) enrolled patients aged 18 to 75 years who were diagnosed with moderate to severe, active UC with an MMS of at least 5 points, central reading of a Mayo endoscopic subscore of at least 2 points, and a documented nonresponse or intolerance to previous treatment.
The participants were assigned 1:1:1:1 to obefazimod 25 mg (1 capsule of 25 mg obefazimod and 1 capsule of placebo), obefazimod 50 mg (1 capsule of 50 mg obefazimod plus 1 capsule of placebo), obefazimod 100 mg (2 capsules of obefazimod 50 mg), or placebo (2 capsules of placebo).
Assessments were performed on treatment days 1, 8, 29, 57 (week 8), 85, and 113 (week 16). The study duration was up to 21 weeks for patients who did not participate in the extension study. Open-label treatment after completion of the randomized trial was up to 96 weeks for long-term extension. The primary endpoint was change in MMS at week 8.
A total of 252 patients were included in the full analysis set (FAS) from August 13, 2019, to April 16, 2021. Sixty-four were assigned to obefazimod 100 mg (mean age, 42.2 years; men, 64%), 63 to obefazimod 50 mg (mean age, 40.2 years; men, 43%), 61 to obefazimod 25 mg (mean age, 41.5 years; men, 66%), and 64 to placebo (mean age, 41.1 years; men, 63%).
At week 8, the least squares mean (LSM) change from baseline in the MMS was -2.9 (95% CI, -3.4 to -2.5) for the obefazimod 100-mg group, -3.2 (-3.7 to -2.7) for the 50-mg group, -3.1 (-3.6 to -2.6) for the 25-mg group, and -1.9 (-2.4 to -1.5) for the placebo group.
The magnitude of improvement in MMS at week 8 for the 3 obefazimod groups was statistically significant compared with placebo, with an LSM difference from placebo of -1.0 (95% CI, -1.7 to -0.3; P =.0039) for the obefazimod 100-mg group, -1.3 (-2.0 to -0.6; P =.0003) for the 50-mg group, and -1.2 (-1.8 to -0.5; P =.0010) for the 25-mg group.
The clinical response, clinical remission, and endoscopic improvement rates at week 8 in the FAS were higher in the 3 obefazimod groups vs placebo.
At week 8, the LSM improvement from baseline in the partial MMS was -2.2 (-2.6 to -1.9) for the 100-mg group, -2.2 (-2.5 to -1.9) for the 50-mg group, and -2.3 (-2.6 to -2.0) for the 25-mg group, and -1.6 (-1.9 to -1.3) for the placebo group.
At week 16, the treatment effects of obefazimod relative to placebo were similar to those at week 8 in the FAS.
Adverse events were reported by 70% of patients in the obefazimod 100-mg group, 60% 63 in the 50-mg group, 53% in the 25-mg group, and 47% in the placebo group during the 16-week induction period. Headache and nausea were the most frequently occurring adverse events.
Interim results from the ongoing long-term extension were reported for the first 48 weeks of open-label treatment with obefazimod 50 mg. In the extension efficacy set, 78 participants either completed 48 weeks (73 patients) or were scheduled to complete 48 weeks (5 patients discontinued). At week 48, 65 (83%) of 78 patients had new or sustained clinical response, and 51 (65%) had new or sustained clinical remission.
The researchers noted that they did not test for a dose-response effect, and the observed data did not indicate the clear existence of an effect.
“The safety and efficacy phase 2b results warrant the continuation of ABX464 clinical development into phase 3 studies,” the study authors noted.
Disclosure: The trial was funded by Abivax. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Vermeire S, Sands BE, Tilg H, et al. ABX464 (obefazimod) for moderate-to-severe, active ulcerative colitis: a phase 2b, double-blind, randomised, placebo-controlled induction trial and 48 week, open-label extension. Lancet Gastroenterol Hepatol. Published online September 5, 2022. doi:10.1016/S2468-1253(22)00233-3