Abivax‘s small, anti-inflammatory molecule ABX464 significantly increased clinical remission and mucosal healing over placebo in patients with moderate to severe active ulcerative colitis resistant to other therapies, top-line results from a Phase 2a clinical trial show.
“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,” Hartmut Ehrlich, MD, CEO of Abivax, said in a press release.
“Based on these exciting results, Abivax will initiate, without delay, a phase 2b dose-ranging study in Europe, with potential input from US KOLs [key opinion leaders] 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,” he said.
The ABX464-101 trial (NCT03093259), which began enrolling participants in November 2017, investigated the safety and effectiveness of ABX464 in 32 people with moderate to severe active ulcerative colitis who had failed or were intolerant to immunomodulators, such as anti-tumor necrosis alpha, Entyvio (vedolizumab), or corticosteroids.
The study was conducted in 15 centers across six European countries: Belgium, France, Germany, Austria, Hungary, and Poland.
Participants were randomized to receive either a 50 mg dose of ABX464, given once daily for eight weeks, or a placebo. They were then followed for one month.
Top-line results of the eight-week treatment showed that ABX464 was safe and well-tolerated. Moreover, the therapy led to clinical remission (according to the total Mayo score) in 35% of the patients, compared with 11% of those on placebo.
Colorectal mucosal healing was also significantly higher in the ABX464 group relative to controls — 50% vs. 11%, respectively. ABX464’s effects were detected within two weeks of treatment.
Overall, a clinical response was reached by 70% of treated patients, compared with 30% of controls. In fact, levels of a well-established biomarker of ulcerative colitis, called calprotectin, were 4.4 times lower following four weeks treatment with ABX464, whereas it was only 1.6 times lower in the control group.
“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 Severine Vermeire, MD, the study’s lead investigator, who is also head of the IBD center at the University Hospitals Leuven in Belgium and former president of the European Crohn’s and Colitis Organization.
“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,” he said.
Patients from four of the participating countries who completed the trial were invited to enroll in a 12-month, open-label follow-up study, the Phase 2 ABX464-102 trial (NCT03368118).
A total of 22 patients have enrolled in the ongoing trial, which is still recruiting participants. So far, the study has confirmed the safety and good tolerability of ABX464. Interim data is expected soon.
ABX464 was first developed as an oral, first-in-class, small molecule to lessen or eliminate the HIV viral reservoirs, with the potential to reduce the long-term viral load of HIV patients.
But the small molecule also showed strong anti-inflammatory properties: In a mouse model of IBD, ABX464 was able to produce long-term effects in preventing symptoms of inflammation in the colon, improving the health of the tissue.
ABX464 was also shown to increase the levels — by up to 10 times — of a small regulatory molecule, a microRNA called miR124, found in blood cells, which has high anti-inflammatory activity.
ABX464 works by binding to the so-called cap binding complex, a mechanism to control gene expression.
“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. They validate our hypothesis that ABX464 novel mechanism of action would result in potent anti-inflammatory properties in patients,” said Jean-Marc Steens, MD, chief medical officer of Abivax.
“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,” he said.