First evidence of long-term efficacy of ABX464 in ulcerative colitis

Prof. Severine Vermeire (University Hospital Leuven, Belgium) presented a 1-year, open-label ABX464 maintenance study conducted in 22 ulcerative colitis (UC) patients without treatment interruption after completion of the randomised, double-blind, placebo-controlled 8 weeks induction study [1]. A total of 19 patients completed the 1-year maintenance study and showed good long-term safety and tolerability of 50 mg given orally over 52 weeks.

ABX464 is an oral drug candidate for UC, among other chronic inflammation disorders, with a novel mechanism of action based on the upregulation of a single microRNA (miRNA-124) with anti-inflammatory properties.

At month 12, an endoscopy to assess clinical remission status (the critical parameter for regulatory authorities) was performed in 16/19 UC patients. During treatment with ABX464, patients reduced their mean total Mayo Score from 8.7 to 1.9 (-78%), their endoscopic subscore from 2.3 to 0.25 (-89%), and their median faecal calprotectin biomarker from 1,044 µg/g to 27.9 µg/g (-97%).

Detailed analysis showed that of the 7/19 patients in clinical remission at the end of the 2-month induction study, 5 were still in clinical remission at the end of the maintenance study (the other 2 patients had missing endoscopy data and could therefore not be assessed). Of the 12/19 patients who were not in clinical remission at the end of the induction study, 7 patients (58%) achieved clinical remission at the end of the maintenance study, while 4 patients had no remission, and 1 had missing endoscopy data. All 3 patients without endoscopy at 12 months had faecal calprotectin levels in the normal range (<50 µg/g), which is indicative of an absence of intestinal inflammation. All 16 patients with endoscopy showed an endoscopic subscore of 0 or 1, indicative of mucosal healing, and in total 12/16 (75%) of the patients undergoing endoscopy achieved clinical remission. The efficacy data from this early study makes ABX464 a very attractive candidate for further development. Furthermore, the data showed that ABX464 maintained the overexpression of miR124 (a critical factor of immunity and inflammation modulated by ABX464) during the 12-month study period.

1. Vermeire S et al. Oral ABX464 QD is safe and efficacious during 52 weeks open label maintenance following a placebo controlled induction study in ulcerative colitis patients. UEG Week Barcelona, Catalonia, Spain, October 19-23, 2019, Abstract LB06.

Posted on 23 October 20198 April 2024