Eldelumab

Abstract: Blockade of the tumor necrosis factor alpha (TNF-α) pathway has been a major advancement for the treatment of inflammatory bowel disease (IBD). A substantial proportion of patients with moderate to severe Crohn’s disease do not have a response to treatment with TNFα antagonists (primary nonresponse), and among patients who do have a response, it is often not sustained (secondary nonresponders) or side effects require discontinuation of medical therapy. As a consequence of this, there is an ongoing need to develop new biologics with different mechanisms of action. This chapter will discuss the major non-anti-TNF-α biological agents in the pipeline that are currently undergoing evaluation to effectively and safely treat patients with IBD.

Abstract: Background and aims This 11-week Phase IIa induction study evaluated the efficacy and safety of eldelumab in patients with active Crohn's disease. Methods Adults with Crohn's Disease Activity Index 220-450 were randomised 1:1:1 to placebo or eldelumab 10 or 20 mg/kg intravenously on Days 1 and 8, and alternate weeks thereafter. All patients underwent ileocolonoscopy at baseline. Patients with active inflammation according to the Simplified Endoscopic Score for Crohn's Disease criteria [the originally planned endoscopy cohort] underwent another ileocolonoscopy at Week 11 at the investigator's discretion. All ileocolonoscopies were centrally read. The primary objective was identification of the eldelumab target exposure for induction of remission [absolute Crohn's Disease Activity Index score Results A total of 121 patients were randomised. The eldelumab exposure-remission relationship was not significant at Week 11. Numerically higher remission and response rates were reported with eldelumab 20 mg/kg [29.3% and 41.5%, respectively] and 10 mg/kg [22.5% and 47.5%] versus placebo [20.0% and 35.0%]. A higher proportion of patients with a baseline Simplified Endoscopic Score for Crohn's Disease > 2 who received eldelumab achieved a 50% improvement in score and greater reductions from baseline endoscopy scores overall versus placebo. Adverse events were comparable across treatment groups. Conclusions No exposure-remission relationship was seen with eldelumab. Eldelumab induction treatment demonstrated trends towards clinical and endoscopic efficacy. Safety was consistent with that reported previously. ClinicalTrials.gov identifier: NCT01466374.