Further clinical development of ABX464 (Abivax, Paris, France), as a novel, first-in-class, orally administered small molecule for the treatment of ulcerative colitis (UC) is justified, based on a randomized study published in Gastroenterology.
Preclinically, ABX464 demonstrated a reduction in dextran sulfate sodium-induced colitis in mice and produced long-term protection while also decreasing miR-124 levels after stopping treatment. Researchers conducted a phase 2a to evaluate the safety and efficacy of ABX464 in patients with moderate to severe UC that involved an 8-week placebo-controlled, double-blind induction phase (ClinicalTrials.gov Identifier NCT03093259) (ABX464, n=20; placebo, n=9) followed by an open-label long-term extension phase (ClinicalTrials.gov Identifier NCT03368118) (prior ABX464, n=11; prior placebo, n=5).
The researchers found that 78.3% of patients receiving ABX464 experienced adverse events (AEs) compared with 55.6% receiving placebo. The most common AEs in the ABX464 group were abdominal pain and headache (17.4% each). The researchers also found that the difference in endoscopic improvement after 8 weeks of treatment was statistically significant. Mean change from baseline in the Mayo Clinic Score (MCS) and the partial Mayo Clinic Score (pMCS) at week 8 were substantially greater in ABX464 patients compared with placebo.
The researchers observed high maintenance of remission rates, with up to 71% of patients in remission on ABX464 at week 8 and experiencing sustained clinical remission until week 52. Of the patients who entered the long-term extension phase without clinical remission, 58.3% achieved this end point after 1 year. Additionally, patients receiving a total of 60 weeks of ABX464 had median fecal calprotectin levels of 20.8 µg/g.
“In conclusion, induction therapy with ABX464 50 mg QD appeared safe and well tolerated,” stated the authors. They added, “After 8 weeks of treatment, ABX464 appeared more effective than placebo in achieving endoscopic improvement and reduction of MCS and pMCS.”
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Vermeire S, Hébuterne X, Tilg H, De Hertogh G, Gineste P, Steens JM; On behalf of the ABX464 Investigators. Induction and long-term follow-up with ABX464 for moderate-to-severe ulcerative colitis: results of phase 2a trial. Gastroenterol. Published online February 24, 2021. doi: 10.1053/j.gastro.2021.02.054