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 a Phase 2a clinical trial, ABX464-101, to treat ulcerative colitis (UC). Patients who completed the induction study had the option to roll over into a 12-month open-label extension study, ABX464-102, in which 22 out of 23 eligible patients were enrolled. 19 patients stayed on treatment for 52 weeks and 16 out of these 19 patients also completed the second year of ABX464 maintenance 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.
Data after the 12-month open-label oral ABX464 Phase 2a maintenance study showed, that 75% of patients with moderate-to-severe active UC who had failed immunomodulators, anti-TNFα, vedolizumab and/or corticosteroids were in clinical remission. During the induction treatment, clinical remission was observed in 35% of ABX464 treated patients (placebo: 11%) and mucosal healing in 50% (placebo: 11%, p = 0.034). ABX464 also demonstrated a rapid onset of action.
To date, app. 800 patients have been treated with ABX464, including those who have been on continuous daily dosing for up to two 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.
ABX464 Mechanism of Action in Ulcerative Colitis
In the Clinic
Based on the positive results from the ABX464-101 trial and the follow-on study ABX464-102, Abivax initiated a Phase 2b study, ABX464-103, in UC for which recruitment was completed in December 2020. The company is also conducting another open-label maintenance study, ABX464-104, in patients who have been enrolled in ABX464-103 to further confirm the long-term safety and efficacy profile of ABX464.
The Phase 2b clinical trials in UC are conducted in 232 patients in 15 European countries, Canada and in the U.S., after an IND was granted by the FDA in January 2020.