Randomised, double-blind, placebo-controlled clinical trial shows statistically significant efficacy based on both clinical and endoscopic endpoints
Abivax has announced topline results from its Phase 2a clinical trial, ABX464-101, conducted in 32 patients for induction treatment of moderate-to-severe ulcerative colitis (UC), refractory to anti-TNF monoclonal antibodies or corticosteroids. In summary, the topline data indicate that ABX464 was safe, well-tolerated, and demonstrated statistically significant efficacy based on both clinical and endoscopic endpoints in this study. The mechanism of action of ABX464 is triggered by an increased expression of miR124, which is a potent anti-inflammatory microRNA.
The final 8-week top-line data from this study are as follows:
Study Measures at Week 8ABX464 Placebo
Clinical remission: 35% 11%
Mucosal healing (central read endoscopy): 50% 11%
Clinical response: 70% 30%
The difference between ABX464 and placebo in colorectal mucosal healing was statistically significant (p<0.03). Furthermore, the onset of the therapeutic effect of ABX464 was rapid, with a difference of the reduction of the partial Mayo score between ABX464 and placebo being observed at the first assessment following treatment for two weeks, which became significant (p<0.02) at eight weeks (likelihood ratio CHI-square test). Similarly, the difference of the reduction of the total Mayo score after eight weeks was statistically significant (p<0.03).
Calprotectin, the best studied biomarker in ulceratice colitis, was markedly reduced (4.4-fold) in patients who received ABX464 in comparison to placebo (1.6-fold) after 4 weeks of treatment.
“Even with the introduction of biologic treatments in recent years, there is still a large unmet medical need in ulcerative colitis, as too many patients do not respond or stop responding to treatment,” said Professor Severine Vermeire, Head of the IBD Center at the University Hospitals Leuven, Belgium, and former President of the European Crohn’s and Colitis Organization and Principal Investigator of the study. “This well-conducted clinical study provides evidence of a robust and consistent efficacy signal of ABX464 across all clinical and endoscopic endpoints as well as on biomarkers evaluated. These results are very promising and we fully endorse the further development of this exciting new oral compound both in ulcerative colitis as well as in other inflammatory diseases including Crohn’s disease.”
ABX464-101 was a randomized, double-blind, placebo-controlled Phase 2a study evaluating the safety and efficacy of ABX464 50mg given orally once-daily for two months in subjects with moderate-to-severe active ulcerative colitis who have failed on immunomodulators, anti-TNFα, vedolizumab and/or corticosteroids. This clinical study was conducted in 15 centers in six European countries: Belgium, France, Germany, Austria, Hungary and Poland.
Twenty-nine of the 32 recruited patients, randomized 2:1 to receive ABX464 as a once daily oral tablet or placebo, have completed the study per protocol, which employed state-of-the art technologies for monitoring potential treatment effects, including numerical recording of the colonoscopies with centralized reading.
As observed in the other studies with ABX464, the product candidate was considered to be safe and well tolerated in ABX464-101. No severe adverse events attributed to ABX464 were reported in the trial.
In four countries, patients who completed the ABX464-101 study had the option to roll over into study ABX464-102, a 12-month open-label follow-up study. Twenty-two patients were enrolled in this maintenance study. Similar to the induction study ABX464-101, ABX464 was safe and well tolerated to date in this ongoing study. A further analysis of interim data from ABX464-102 is scheduled and will be reported in the coming months.
“These results have exceeded our expectations given the statistically significant, strong efficacy already observed in this phase 2a study, in patients refractory to available therapies including anti-TNF monoclonal antibodies,” said Dr Jean-Marc Steens, Chief Medical Officer of Abivax. “They validate our hypothesis that ABX464 novel mechanism of action would result in potent anti-inflammatory properties in patients. Like other chronic inflammatory diseases, ulcerative colitis is a debilitating disease that greatly affects patients’ quality of life and warrants expensive innovative therapies. We look forward to developing and potentially market ABX464 as a well-tolerated oral treatment for this large patient population."
It is estimated that close to 1 million patients with ulcerative colitis live in the US, 650.000 in the EU and >2.7 million globally. Pharmaceutical sales for this disease in the major global markets are estimated to be around US$5.5 billion in 2017. For inflammatory bowel disease, which includes both ulcerative colitis and Crohn’s disease, the sales in the major global markets are estimated to be around US$15 Billion for the same period.
“These impressive clinical trial data are indicative of the potential for ABX464’s unique mechanism of action to safely and effectively bring substantial clinical benefit to patients who are not adequately helped by currently available therapeutics and are struggling from the devastating consequences of this inflammatory disease,” said Professor Hartmut Ehrlich, Chief Executive Officer at Abivax. “Based on these exciting results, Abivax will initiate, without delay, a phase 2b dose-ranging study in Europe, with potential input from US KOLs and FDA on study design. Furthermore, these data strongly encourage us to pursue phase 2 clinical trials in other inflammatory indications including Crohn’s disease.”