Model ABX464 - 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 2021, Abivax communicated the top-line results of its randomized, double-blind and placebo-controlled Phase 2b induction 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 top-line induction results, preliminary data from the first 51 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.

In September 2020, Abivax reported promising results, showing long-lasting efficacy and continued good safety after the two years open-label oral ABX464 Phase 2a maintenance study in subjects with moderate-to-severe active UC who were all intolerant and/or refractory to at least one existing treatment.

69% (11/16) of patients were in clinical remission and 94% (15/16) benefited from a clinical response. 44% (7/16) had endoscopic remission consisting of complete disappearance of colon/rectum lesions (endoscopic Mayo score=0). Median fecal calprotectin, the key biological marker of UC disease activity, which was normalized during the first year of treatment, remained at 31.6 µg/g (normal levels are below 50 µg/g).

The two-year open-label ABX464 maintenance study was conducted in 19 patients without treatment interruption after completion of the randomized, double-blind, placebo-controlled 8 weeks induction study and the one-year open label maintenance study. A total of 16 patients completed the two-year ABX464 open label maintenance study and showed long-term safety and tolerability of 50mg given orally.

To date, app. 850 patients have been treated with ABX464, including those who have been on continuous daily dosing for up to 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.

Based on the positive results from the Phase 2a and Phase 2b studies, Abivax plans to advance ABX464 into a Phase 3 clinical program by the end of 2021.

• Phase 2a data from 12- and 24-months maintenance study reported
• Phase 2b data from induction study reported