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OP21 ABX464 is safe and efficacious in a proof-of-concept study in ulcerative colitis patients

S. Vermeire1, X. Hébuterne2, P. Napora3, M. Wisniewska-Jarosinska4, G. Kiss5, A. Bourreille6, Z. Przemysław7, J. Nitcheu8, P. Gineste8, J-M. Steens*8, H. Ehrlich8

1University Hospitals Leuven, Leuven, Belgium, 2CHU Nice Hopital Archet 2, Nice, France, 3Piotr Napora Centrum Badań Klinicznych Lekarze Sp.p., Wroclaw, Poland, 4SANTA FAMILIA, Centrum Badań, Profilaktyki i Leczenia, Lodz, Poland, 5Vasútegészségügyi Nonprofit Közhasznú Kft, Debrecen, Hungary, 6CHU Nantes Hotel Dieu, Nantes, France, 7KO-Med, Lublin, Poland, 8Abivax, Paris, France

Background

Despite the availability of new drugs in IBD, there is still a high unmet medical need for patients suffering from ulcerative colitis. ABX464 has potent anti-inflammatory properties impacting the expression of miR124 as shown in HIV studies. We performed a first-in-disease Phase 2a study with ABX464 in patients with moderate-to-severe ulcerative colitis intolerant and/or refractory to existing treatments.

Methods

The study was performed in 15 European centres. A total of 32 patients were randomised (2:1) to ABX464 50 mg QD orally or placebo for 8 weeks. The primary endpoint was safety of ABX464 and key secondary endpoints included remission (assessed a rectal bleeding sub-score = 0 and an Endoscopy sub-score ≤1 and at least one-point decrease in stool frequency sub-score from baseline to achieve a stool frequency sub-score ≤1), endoscopic improvement (Mayo endoscopic score of 0 or 1), and clinical response and histological healing. Centrally-read endoscopy with histopathology were performed at Day 0 and Day 56. After the blinded induction phase, patients had the option to roll over into a 52-week open-label 50 mg QD ABX464 study.

Results

Total of 29 (90.6%) patients (20 randomised to ABX464 and 9 to placebo) completed the induction study. Baseline demographics and characteristics showed well-balanced groups. The overall safety profile of ABX464 was overall very good with no serious adverse events (SAE). Safety profile was similar to the one seen in the clinical development in the HIV reservoir reduction indication. Main efficacy results are presented below.

ABX464 (n = 20)Placebo (n = 9)p value
Clinical remission35%11%0.16
Endoscopic improvement50%11%0.03
Clinical response70%33%0.06
Total Mayo score reduction−53%−27%0.03
Partial Mayo score reduction−62%−32%0.02
Faecal calprotectin decrease >50%75%50%
miRNA124-fold expression7.691.460.004

ABX464-101 study endpoints results at Day 56.

The interim data from the 52-week maintenance study show further improvement of Partial Mayo Score and reduction in faecal calprotectin.

Twenty-two patients were included in the 52 weeks maintenance study. The interim analysis with a mean maintenance treatment duration of 5.1 months (max: 9.0 months; min: 3.5 months) showed further improvement in both Partial Mayo score and faecal calprotectin levels.

Conclusion

In this Phase 2a study in patients with moderate-to-severe UC, ABX464 50 mg QD orally for 8 weeks was safe and well tolerated. Clinical, endoscopy, histopathology, and biomarker analysis all changed in a consistent way and all in favour of ABX464. These data support a Phase 2b multi-centre placebo-controlled dose-ranging study in UC and a Phase 2a study in Crohn’s disease.