Eltrekibart Shows Promising Signal in Phase 2 HS Trial

Eltrekibart, an investigational monoclonal antibody targeting neutrophil-driven inflammation, demonstrated a promising efficacy signal and an acceptable safety profile in adults with moderate-to-severe hidradenitis suppurativa (HS) in a randomized, double-blind, placebo-controlled phase 2 trial.

The study enrolled adults with moderate-to-severe HS and randomized participants 2:1 to receive intravenous eltrekibart 600 mg or placebo every two weeks for 16 weeks, followed by an open-label extension in which all participants received eltrekibart. The primary endpoint was achievement of Hidradenitis Suppurativa Clinical Response (HiSCR50), defined as a ≥50% reduction in abscess and inflammatory nodule count without worsening of abscesses or draining fistulas.

At week 16, 48.9% of eltrekibart-treated participants achieved HiSCR50 compared with 31.8% of those receiving placebo. Although this difference favored eltrekibart, it did not reach statistical significance in the prespecified primary analysis (P = .19; 95% CI −7.3 to 41.4). To address the known challenge of high placebo response rates in HS trials, investigators conducted a prespecified Bayesian augmented control analysis incorporating matched historical placebo data from prior phase 3 HS studies. In this analysis, 65.6% of eltrekibart-treated participants achieved HiSCR50 compared with 32.3% of the augmented-control placebo group, yielding a 99.9% posterior probability of eltrekibart superiority and a 61.9% probability of a ≥30% treatment difference.

Key secondary endpoints further supported an efficacy signal. Participants treated with eltrekibart experienced a significantly greater reduction in total abscess and inflammatory nodule count at week 16 compared with placebo (least squares mean change −6.52 vs −1.85 lesions; P = .02). Improvements in disease severity measures, including higher-threshold clinical responses and severity scores, numerically favored eltrekibart, though these differences did not reach statistical significance.

In contrast, improvement in HS-associated skin pain was similar between treatment groups at week 16, with no statistically significant difference observed between eltrekibart and placebo. This finding is consistent with prior HS trials in which lesion count improvements have not always translated into parallel pain reductions.

Eltrekibart is a humanized monoclonal antibody designed to neutralize all seven ELR-positive CXC chemokine ligands that signal through CXCR1 and CXCR2. By targeting a shared epitope across these ligands, eltrekibart aims to reduce neutrophil chemotaxis and downstream inflammatory activity without broadly suppressing other neutrophil functions. Given the established role of neutrophil-driven inflammation in HS pathogenesis, this mechanism represents a differentiated therapeutic approach compared with currently approved biologics.

Safety findings were generally consistent with expectations for biologic therapies in HS. During the double-blind treatment period, treatment-emergent adverse events occurred in 53.3% of eltrekibart-treated participants and 40.9% of placebo-treated participants, with most events reported as mild or moderate in severity. Infections were reported in 13.3% of participants receiving eltrekibart and 18.2% of those receiving placebo. Serious adverse events were uncommon, and no deaths occurred during the study. Discontinuations due to adverse events were rare, and no new or unexpected safety signals were identified.

Key Takeaways:

• Eltrekibart showed a promising efficacy signal in moderate-to-severe hidradenitis suppurativa.
• Bayesian augmented control analysis strengthened the evidence of clinical benefit.
• The safety profile was acceptable and consistent with expectations for biologic therapies, with mostly mild-to-moderate adverse events and no new or unexpected safety signals identified.