IL6 trans-signaling blockade holds therapeutic promise in IBD

The interleukin (IL) 6 proinflammatory trans-signaling inhibitor olamkicept appears safe and effective in the treatment of patients with inflammatory bowel disease (IBD), according to the results of the phase IIa FUTURE trial.

A total of 16 patients (median age 25.5 years, 68.8 percent female) with active IBD (ulcerative colitis [UC], n=9; Crohn’s disease [CD], n=7) received up to seven infusions of 600-mg olamkicept (sgp130Fc) every 2 weeks for 12 weeks.

Clinical disease activity was assessed using Mayo score for UC or clinical disease parameters for CD (CDAI) for CD. Three patients (19 percent; two with UC, one with CD) achieved clinical remission, and seven (44 percent; five with UC, two with CD) achieved clinical response at week 14. Of note, the three patients with clinical remission also showed endoscopic remission.

Clinical efficacy corresponded with target inhibition (reduction of phosphorylated STAT3) and marked transcriptional changes in the inflamed mucosa. An olamkicept-specific transcriptional signature was detected, and this signature was distinct from remission signatures of anti–tumour necrosis factor (infliximab) or anti-integrin (vedolizumab) therapies.

The incidence of adverse events (AEs) was quite high, seen in 13 patients (81 percent). AEs were not drug-related and not indicative of severe immune suppression. The most common AEs were seasonal upper respiratory tract infections (laryngitis or rhinitis), recurrence of herpes labialis, and skin and subcutaneous disorders (eczema or erythema).

There were no abnormal trends observed in clinical safety laboratory measurements or vital signs. Serious AEs were documented in five patients (31 percent) and included an episode of atrial fibrillation and unspecific weakness.

In light of the findings, olamkicept should undergo full clinical development as a potential immunoregulatory therapy for IBD.