eldelumab (BMS-936557) / BMS - LARVOL DELTA

IP-10 acts early in CV-A16 infection to induce BBB destruction and promote virus entry into the CNS by increasing TNF-α expression. (PubMed, Front Immunol) - "Our results revealed that the expression levels of Claudin5, Occludin, ZO-1 and VE-Cadherin were notably decreased in CV-A16-infected HUVECs, but these indicators were restored in CV-A16-infected HUVECs with Eldelumab treatment...In addition, IP-10 and TNF-α were observed to reduce junctional complexes and enhance virus entry into the CNS. Taken together, this study provides the first evidence that CV-A16 activates the IP-10/TNF-α regulatory axis to cause BBB damage and accelerate the formation of neuroinflammation in infected hosts, which not only provides a new understanding of the neuropathogenesis caused by CV-A16, but also offers a promising target for the development of CV-A16 antiviral drugs."

Journal • Infectious Disease • Inflammation • CDH5 • CLDN5 • CXCR3 • IFIH1 • IFNG • OCLN • TJP1 • TLR3 • TNFA

Phase IIB, randomized, placebo-controlled evaluation of the efficacy and safety of induction therapy with eldelumab (anti-IP-10 antibody; BMS-936557) in patients with active ulcerative colitis (DDW 2014) - Presentation time: Tuesday,  8:00AM - 9:30AM; Abstract #865; P2b, N=252; Sponsor: Bristol-Myers Squibb; NCT01294410; "Induction treatment with eldelumab 15 or 25 mg/kg did not achieve the primary endpoint, although there were trends towards efficacy in the overall population and in patients who were anti-TNF naïve. Safety signals were consistent with those reported previously for eldelumab."

P2b data • Inflammatory Bowel Disease

Anti-IP-10 antibody (BMS-936557) for ulcerative colitis: A phase II randomised study (Gut) - PMID: 23461895; P2, N=109; Sponsor: Bristol-Myers Squibb; NCT00656890; "Prespecified primary and secondary endpoints were not met; clinical response rate at Day 57 was 52.7% versus 35.2% for BMS-936557 versus placebo (p=0.083), and clinical remission and mucosal healing rates were 18.2% versus 16.7% (p=1.00) and 41.8% versus 35.2% (p=0.556), respectively. However higher BMS-936557 steady-state trough concentration (Cminss) was associated with increased clinical response (87.5% vs 37.0% (p<0.001)..."

P2 data • Inflammatory Bowel Disease

Phase IIa, randomized, placebo-controlled evaluation of the efficacy and safety of induction therapy with eldelumab (Anti-IP-10 Antibody; BMS-936557) in patients with active Crohn’s disease (DDW 2015) - Presentation time: 8:30 am - 8:45 am Tue, May 19; Abstract #827; P2, N=121; NCT01466374; Sponsor: Bristol-Myers Squibb; "At Week 11, numerically higher remission and response rates were reported with eldelumab 10 mg/kg (22.5% and 47.5%, respectively) and 20 mg/kg (29.3% and 41.5%) compared with placebo (20.0% and 35.0%). Clinical remission and response rates were higher in anti-tumor necrosis factor (TNF)-naïve patients versus anti-TNF failures across both eldelumab treatment arms..."

P2a data • Inflammatory Bowel Disease

Response to Placebo, Measured by Endoscopic Evaluation of Crohn's Disease Activity, in a Pooled Analysis of Data from 5 Randomized Controlled Induction Trials. (PubMed, Clin Gastroenterol Hepatol) - "Rates of response and remission to placebo, determined by centrally-read endoscopy, in induction trials of therapies for CD are low. These estimates are important for sample size calculations for randomized placebo-controlled trials that use the Simple Endoscopic Score for CD as an endpoint. They also provide a benchmark to interpret findings from non-placebo controlled, prospective, randomized, unblinded trials."

Journal • Retrospective data