ABX464 for Ulcerative Colitis
ABX464 is an oral, first-in-class, small molecule that has demonstrated safety and profound anti-inflammatory activity in preclinical trials and in Phase 2a and Phase 2b induction trials to treat ulcerative colitis (UC). Patients who completed the induction studies had the option to roll over into the respective open-label extension studies.
In May and September 2021, Abivax communicated the top-line and full results, respectively, of its randomized, double-blind and placebo-controlled Phase 2b trial conducted in 15 European countries, the US and Canada in 254 patients. The primary endpoint (statistically significant reduction of Modified Mayo Score) was met with once-daily ABX464 (25mg, 50mg, 100mg) at week 8.
Further, all key secondary endpoints, including endoscopic improvement, clinical remission, clinical response and the reduction of fecal calprotectin showed significant difference in patients dosed with ABX464 compared to placebo. Importantly, ABX464 also showed rapid efficacy in patients who were previously exposed to biologics and/or JAK inhibitors treatment.
In addition to the induction results, preliminary data from the first 101 patients treated with 50mg ABX464 in the Phase 2b open-label maintenance study showed increased and durable clinical remission and endoscopic improvement after 48 weeks of treatment.
To date, app. 850 patients have been treated with ABX464, including those who have been on continuous daily dosing for more than three years. Based on our observations and, in comparison with currently available therapeutic options, ABX464 shows a very good clinical safety and tolerability profile along with evidence of superior long-term efficacy.
Because of its ability to greatly upregulate the production of a unique RNA splicing product and anti-inflammatory agent, miR-124, ABX464’s mechanism of action is unique and has shown promise in clinical trials in its ability to bring patients into remission and heal inflammatory lesions in UC.
97.7% (217/222) of all patients who completed the Phase 2b induction study, irrespective of treatments or treatment outcome during the induction phase, enrolled in the subsequent open-label maintenance study to evaluate the long-term safety and efficacy profile of ABX464 for up to two years.
Among the subset of 101 patients for whom 1 year maintenance data is currently available (cut-off date: September 15, 2021), 28 had entered the maintenance study already in clinical remission: 23/28 (82.1%) of these patients stayed in clinical remission and only 5/28 patients (17.9%) lost clinical remission during this first year of maintenance.
Importantly, 36/73 patients (49.3%) who were not in clinical remission at the end of induction achieved a de novo clinical remission during the first year of maintenance.
Remarkably, the clinical remission rate for patients who did not show at least a clinical response at the end of the induction phase was 55.9% (PP) and 50% (ITT) after 48 weeks of treatment, demonstrating that long-term administration of ABX464 provided substantial clinical benefits also for these patients.
In addition to the phase 2b maintenance results, Abivax recently also reported efficacy data from its ongoing phase 2a maintenance study in UC.
15 out of the 22 patients who were initially enrolled into the phase 2a maintenance study completed the third year of treatment with 50mg once daily oral ABX464 as of June 29, 2021.
Among the 13 patients who had centrally read endoscopies at the completion of year 3, 11 patients (85%) were still in clinical remission, of which 7 patients (54%) had an endoscopic remission (endoscopic subscore=0) and 11 patients had an endoscopic remission or improvement (endoscopic subscore=0 or 1).
ABX464 Mechanism of Action in Ulcerative Colitis
In the Clinic
Based on the positive results from the Phase 2a and Phase 2b studies, Abivax plans to advance ABX464 into a global Phase 3 clinical program.