ABX464 Benefits Ulcerative Colitis Patients at Week 8

Severine Vermeire, MD

ABX464 (obefazimod), a small molecule that selectively upregulates miR-124 in immune cells, can help improve symptoms for patients with ulcerative colitis.

A team, led by Severine Vermeire, MD, Department of Gastroenterology and Hepatology, University Hospitals Leuven, assessed ABX464 as a treatment for patients with moderate-to-severe, active ulcerative colitis.

The Study

In the phase 2b, double-blind, randomized, placebo-controlled induction trial, the investigators examined 254 patients from 95 hospitals and health care centers in 16 countries between August 13,2019 and April 16, 2021. Each participant was aged 18-75 years with a diagnosis of moderate-to-severe, active ulcerative colitis and a modified Mayo score of 5 points or higher with a documented non-response or intolerance to previous treatments.

The patients were randomly assigned to either once daily oral ABX464 100 mg (n = 64), ABX464 50 mg (n = 63), ABX464 25 mg (n = 63), or matched placebo (n = 64).

The randomization was stratified according to study site and whether the patient had previous exposure to second-line treatment with biologics or JAK inhibitors.

Endpoints

The investigators sought primary endpoints of the change from baseline in modified Mayo score at week 8.

They also conducted the primary efficacy analysis in the full analysis set, defined as all randomly assigned patients who received at least 1 dose of study treatment and had baseline data for at least 1 efficacy variable and was analyses according to the principles on intention-to-treat.

In the safety analysis, the investigators looked at the patients who had been randomly assigned and received at least 1 dose of study treatment.

Efficacy

There were 2 patients in the ABX464 25 mg excluded from the full analysis set.

At week 8, the least squares mean change from baseline in modified Mayo scores was -2.9 (95% CI, -3.4 to -2.5) for the ABX464 100 mg group, –3·2 (95% CI, –3·7 to –2·7) for the ABX464 50 mg group, –3·1 (95% CI, –3·6 to –2·6) for the ABX464 25 mg group, and –1·9 (95% CI, –2·4 to –1·5) for placebo group.

The magnitude of the difference in modified Mayo score from baseline was significantly greater in all ABX464 groups compared to placebo (P = 0·0039 for ABX464 100 mg vs placebo; P = 0.0003 for ABX464 50 mg vs placebo; and P = 0.0010 for ABX464 25 mg vs placebo).

Safety

For safety, headaches were the most frequently reported adverse event, occurring in 30% (n = 19) of the 50 mg group, 21% (n = 13) of the 25 mg group, and 8% (n = 5) of the placebo group. In addition, severe headaches of a grade 3 or higher was reported in 5% (n = 3) of patients in the ABX464 group 100 mg group, 3% (n = 2) of the ABX464 50 mg group, 2% (n = 1) of the ABX464 25 mg group, and none in the placebo group.

The only serious adverse event reported for at least 2 patients in any group was ulcerative colitis (1 in each of the ABX464 100 mg and 50 mg groups, and 3 [5%] in the placebo group).

“All doses of ABX464 significantly improved moderate-to-severe, active ulcerative colitis compared with placebo, as measured by changes in MMS from baseline to week 8. A phase 3 clinical program is ongoing,” the authors wrote.

The 96 week open-label extension is going.

The study, “ABX464 (obefazimod) for moderate-to-severe, active ulcerative colitis: a phase 2b, double-blind, randomized, placebo-controlled induction trial and 48 week, open-label extension,” was published online in The Lancet Gastroenterology & Hepatology.