ABX464 Results in Clinical Remission for Ulcerative Colitis Patients

More patients also achieved endoscopic and histologic remission in the treatment group compared to the placebo group.

Early phase data shows higher rates of ulcerative colitis will achieve clinical remission and improvements treated with ABX464 when compared to placebo.

A team, led by Severine Vermeire, MD, PhD, Department of Gastroenterology, University Hospitals Leuven, recently presented data from an induction phase and open-label extension study showing the treatment results in primary endpoints and should be a candidate for later phase trials.

The Drug

ABX464 is a novel, orally administrated small molecule that could treat ulcerative colitis by interacting with CBC, allowing specific splicing of anti-inflammatory miR-124, leading to a cascade of modulating pro-inflammatory cytokines. ABX464 has also demonstrated a dual mechanisms of action in HIV by generating miR-124 and splicing viral RNA that shows promise in its ability to treat inflammatory bowel disease (IBD).

The randomized study included both an 8-week placebo-controlled, double-blind induction period, as well as an open-label long-term extension phase involving adults as old as 75 years old with moderate to severe active ulcerative colitis.

The mean age of the induction phase was 43.3 years old, with 62.5% of the patient population being male.

The patients were randomized at a 2-1 ratio to receive either oral 50 mg ABX464 (n = 23) or placebo (n = 9) for 8 weeks in the induction phase.


The researchers sought primary endpoints of safety, assessed as the rate of
TEAEs and efficacy, which included the proportion of patients achieving clinical remission at week 8 compared to placebo, changes from baseline to week, Mayo Clinic Scores (MCS) and Partial Mayo Clinic Scores (pMCS), rates of endoscopic remission and improvement, changes from baseline to week 8 in (histopathological) Geboes score, change in fecal calprotectin, and miR-124 expression.

In the long-term extension phase, the researchers sought primary endpoints of the long-term safety of the treatment, and additional efficacy endpoints that included clinical and endoscopic rates of response and remission.

Of the 29 patients who completed the induction phase, 20 were in the treatment group. In addition, 22 of the 29 patients in the induction phase continued into the long-term extension trial.


Overall, 78.3% of the patients in the treatment group experienced adverse events, higher than the 55.6% of the placebo group that experienced an adverse event. The most common adverse events in the ABX464 arm of the study were abdominal pain and headache, both experienced by 17.4% of the patients.

In addition, 1 patient in the induction phase prematurely withdrew because of transaminase elevation 3x ULN. In addition, the most common adverse events through 24 months were nasopharyngitis and abdominal pain, each found in 31.3% of the treatment group.

There were no deaths in the study.

Remission and Improvement

Clinical remission was achieved by 35% of the treatment group patients at week 8, compared to just 11.1% of the placebo group.

For clinical response, 70% of the ABX464 group achieved this endpoint, which was also higher than the 33.3% of placebo patients that achieved a clinical response.

The researchers also found 50% and 10% of the treatment group achieved an endoscopic improvement and remission, respectively, compared to 11.1% each for the placebo group. For the 11 patients who achieved endoscopic improvement, all also showed histologic improvement.

“In conclusion, induction therapy with ABX464 50 mg QD appeared safe and well tolerated,” the authors wrote. “After 8 weeks of treatment, ABX464 appeared more effective than placebo in achieving endoscopic improvement and reduction of MCS and pMCS. Maintenance therapy with ABX464 sustained remission and brought additional patients into remission.”

The study, “Induction and long-term follow-up with ABX464,” was published online in Gastroenterology.