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 completed Phase 2a proof-of-concept study to treat lesions in ulcerative colitis.
In September 2018, Abivax reported exciting topline data from a 2-month proof-of-concept induction study of ABX464 in patients with moderate to severe ulcerative colitis (see data in table below). The company is currently conducting a 12-month extension (maintenance) study called ABX464-102, from which 6-month interim results were presented at the annual ECCO conference in Denmark in March 2019. Prior to completion of the 12-months of ABX464-102, a second year extension of ABX464-102 was approved in all countries participating in the trial with the longest patient having been treated with ABX464 for over 16 months.
When evaluated in a Phase 2a Proof-of-Concept study, ABX464-101, ABX464 demonstrated both safety and statistically significant efficacy based on both clinical and endoscopic endpoints with 35% of the patients achieving a clinical remission (placebo: 11%) and 50% of patients achieving mucosal healing (placebo: 11%), (p=0.034)
Because of its ability to greatly upregulate 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 to remission and heal inflammatory lesions in ulcerative colitis.
In the Clinic
ABX464 has completed a Phase 2a proof-of-concept study, ABX464-101, aimed at evaluating the safety and efficacy of ABX464 50 mg given once daily versus placebo for two months in subjects with moderate-to-severe active ulcerative colitis (UC) who have failed or are intolerant to immunomodulators, anti-TNFα, vedolizumab and/or corticosteroids. This study revealed a statistically significant difference in mucosal healing, a hallmark of successful treatment, between ABX464 and placebo (50% vs. 11%), and also demonstrated a rapid onset of action for ABX464.
Based on the positive results from the ABX464-101 study, Abivax is in the process of initiating a Phase 2b study of ABX464 in ulcerative colitis in the second quarter of 2019. The company is also conducting ABX464-102, a 12-month open-label study focusing on patients from study ABX464-101. A total of 22 patients were enrolled in ABX464-102 and 6-month interim results from this trial were presented on the first quarter of 2019. 9-month interim results will be presented at the Digestive Disease Week meeting in San Diego in May 2019.