Obefazimod for Ulcerative Colitis

Obefazimod 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 administration of obefazimod (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 obefazimod compared to placebo. Importantly, obefazimod also showed rapid efficacy in patients who were previously exposed to biologics and/or JAK inhibitors treatment.

In addition to the induction results, the analysis of the maintenance study after one and two years of treatment demonstrate clinical remission rates of 55.3% and 52.5% in 217 ulcerative colitis patients treated with once-daily oral 50mg obefazimod.

Because of its ability to greatly upregulate the production of a unique RNA splicing product and anti-inflammatory agent, miR-124, the mechanism of action of obefazimod 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% (n=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 open-label maintenance study to evaluate the long-term safety and efficacy profile of obefazimod for up to two years.

Among the 217 patients who completed the 8-week induction study of 50mg once-daily oral dosing with obefazimod, 49 had entered the maintenance study already in clinical remission. 73.1% (n=38) out of these 49 patients stayed in clinical remission during this first year and 67.3% (n=33) also during the second year of maintenance treatment.

It is remarkable that 48.2% (n=81/168) patients who were not in clinical remission at the end of induction achieved a de novo clinical remission during the two-year maintenance treatment.

Furthermore, the clinical remission rate for patients who did not show at least a clinical response at the end of the induction phase was 43.0% (n=40) after two years of treatment, demonstrating that long-term administration of obefazimod provided substantial clinical benefits also for these patients.

As of November 2022 (last safety data cut-off), 1,074 patients and volunteers were treated with obefazimod, of which 209 patients have been treated with 50mg obefazimod for one year or more. To date, no signal of opportunistic infections or malignancies have been detected.

The phase 2b induction trial and 48-week extension results of obefazimod in UC were published in the prestigious, peer-reviewed journal “The Lancet Gastroenterology and Hepatology” with the title “ABX464 (obefazimod) for moderate to severe active ulcerative colitis: a randomised, placebo controlled phase 2b induction trial and 48 week, open-label extension“.

1,200 moderate to severe UC patients across 36 countries will take part in the pivotal phase 3 program which consists of two induction studies and a subsequent maintenance study (ABTECT-1 and ABTECT-2 induction trials – ABX464-105 and ABX464-106 – and ABTECT maintenance trial – ABX464-107). These three pivotal studies are all randomized, double-blind and placebo controlled, using independent and central review of the video-taped endoscopies. The primary efficacy endpoint assessed at week 8 (induction) and at week 44 (maintenance) will be clinical remission according to the modified Mayo Score, as required by FDA.

In consultation with international regulators, including FDA and EMA, obefazimod 25mg and 50mg will be investigated in phase 3 for the treatment of UC in advanced therapies (AT) naïve and in AT-failure patients to support the future submission of marketing authorizations.