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.
In October 2019, Abivax reported exciting new data showing 75% of patients in clinical remission after the 12-month open-label oral ABX464 Phase 2a maintenance study in subjects with moderate-to-severe active UC who had failed immunomodulators, anti-TNFα, vedolizumab and/or corticosteroids. The one year open-label ABX464 maintenance study was conducted in 22 patients without treatment interruption after completion of the randomized, double-blind, placebo-controlled 8 weeks induction study. A total of 19 patients completed the one-year ABX464 open label maintenance study and showed long-term safety and tolerability of 50mg given orally over 52 weeks.
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 and the efficacy was similar in patients naïve or resistant to biologics (e.g. anti-TNF-∝ or vedolizumab).
To date, over 300 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.
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 and enrolled the first patient in August 2019. 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 currently conducted in 232 patients in 15 European countries, Canada and more recently in the U.S., after an IND was granted by the FDA in January 2020.