Data from a proof of concept study presented at the Congress of the European Crohn’s and Colitis Organisation indicated that ABX464, a novel drug candidate, was safe and efficacious in the treatment of ulcerative colitis.
Researchers have previously studied the drug as an antiretroviral for HIV.
Jean-Marc Steens, MD, chief medical officer at Abivax, the drug’s manufacturer, told Healio Gastroenterology and Liver Disease that studies in HIV showed that the drug could reduce the HIV DNA found in the HIV reservoir, which is mostly located in the gastrointestinal tract. The HIV reservoir is a source of HIV DNA integrated into infected cells and leads to several comorbidities, including inflammation, that persist in patients even if their disease is well-controlled and well-suppressed.
“That is what sparked our idea,” Steens said. “What if our drug had anti-inflammatory properties? So, we started in vitro in cells, and indeed, we saw it had some anti-inflammatory properties.”
Research led to a 2-month phase 2a study comprising 32 patients with moderate-to-severe UC who were intolerant and/or refractory to existing treatments. Steens presented data from this proof of concept study at ECCO, in addition to interim data from a 12-month extension study with 22 patients of the original 32 patients in the induction study.
Investigators randomly assigned patients to receive either ABX464 50 mg once a day or placebo for 8 weeks. The primary endpoint of the study was safety of the drug, while remission, endoscopic improvement, clinical response and histologic healing were key secondary endpoints.
Twenty-nine patients completed the induction study (ABX464 n = 20; placebo n = 9).
Investigators found that the drug was safe and well-tolerated by patients. There were no serious adverse events, and the safety profile was similar to the one observed during the drug’s development in HIV.
Compared with placebo, ABX464 produced better rates of clinical remission (11% vs. 35%), endoscopic improvement (11% vs. 50%) and clinical response (33% vs. 70%). ABX464 also produced greater reductions in Mayo scores and helped more patients achieve a fecal calprotectin decrease of more than 50%.
Interim data from the 6-month mark of a 12-month maintenance study (n = 22) showed further improvement in both partial Mayo score and fecal calprotectin levels.
“When we look at the data, in terms of remission and endoscopic healing especially, it is obvious that these are very encouraging,” Steens said. “Of course, this needs to be confirmed in larger studies, but reaching statistical significance in a phase 2a study is already a major accomplishment.” – by Alex Young
Reference: Vermeire S, et al. Abstract OP 21. Presented at: Congress of the European Crohn’s and Colitis Organisation; Mar. 7-9, 2019; Copenhagen.
Disclosure: Steens reports that he is an employee of and a shareholder in Abivax. He also reports being a shareholder of GSK. Please see the ECCO disclosure database for all other authors’ relevant financial disclosures.