A Phase II Open-Label Study of Bermekimab in Patients with Hidradenitis Suppurativa Shows Resolution of Inflammatory Lesions and Pain

Abstract

The objective of this study was to evaluate the safety and efficacy of bermekimab, an IL-1a inhibitor, in the treatment of hidradenitis suppurativa (HS). This study was a phase II, multicenter, open-label study of two dose cohorts of bermekimab in patients with moderate-to-severe HS who are naïve to or have failed prior anti-TNF therapy. Patients with HS (n ¼ 42) were divided into groups A and B based on whether or not they had previously failed an anti-TNF therapy. In group A (n ¼ 24), bermekimab was administered subcutaneously at a dose of 400 mg weekly (13 doses) in patients who had previously failed anti-TNF therapy; in group B (n ¼ 18), bermekimab was administered subcutaneously at a dose of 400 mg weekly (13 doses) in patients who were anti-TNF naïve. Bermekimab, previously found to be effective in treating HS, was evaluated using a subcutaneous formulation in patients with HS naïve to or having failed anti-TNF therapy. There were no bermekimab-related adverse events with the exception of injection site reactions. Bermekimab was effective despite treatment history, with 61% and 63% of patients naïve to and having failed anti-TNF therapy, respectively, achieving HS clinical response after 12 weeks of treatment. A significant reduction in abscesses and inflammatory nodules of 60% (P < 0.004) and 46% (P < 0.001) was seen in anti-TNF naïve and anti-TNF failure groups, respectively. Clinically and statistically significant reduction was seen in patients experiencing pain, with the Visual Analogue Scale pain score reducing by 64% (P < 0.001) and 54% (P < 0.001) in the anti-TNF naïve and anti-TNF failure groups, respectively. IL-1a is emerging as an important clinical target for skin disease, and bermekimab may represent a new therapeutic option for treating moderate-to-severe HS.

Defining Epidermal Stem Cell Fate Infidelity and Immunogenicity in Hidradenitis Suppurativa at the Single-Cell Resolution

“…Third, we showed that IL1A_IL1R interactions are not present in our HS samples; however, IL1B_IL1R is detected in Ax1 patient, whose epidermis also express low level of IL1B, which indicates that blocking IL1R may be effective in some patients, while blocking IL1A may not. Again, this is corroborated by the contrasting results of small scale clinical trials of IL-1B and IL-1a blockade in clinical disease [40][41][42] . Lastly, we showed that ITGAL(LFA-1)_ICAM1 interaction is minimally detectable in perilesional epidermis of one patient (Ax1), and not others, confirming that LFA1 blocking may not be effective for HS treatment 43 .…”

Contribution of plasma cells and B cells to hidradenitis suppurativa pathogenesis

“…Instead, we found evidence for increased expression of IL36A and IL36G ( Figure 1 ). In this context, case reports targeting the IL-1 axis in HS have provided mixed results, with some showing modest improvement ( 23 , 24 ) and others showing no improvement ( 25 ). No clinical trial data exist on the use of anti–IL-6 agents in HS, but one study noted development of HS in a patient undergoing the anti–IL-6 treatment tocilizumab ( 26 ).…”

Cytokine Pathways and Investigational Target Therapies in Hidradenitis Suppurativa

“…Bermekimab (MABp1) is an anti-IL-1α human monoclonal antibody [ 123 ]. Forty-two patients were enrolled in a phase 2 clinical trial, reporting that bermekimab was effectively inducing a clinical response after 12 weeks of treatment [ 123 ].…”

“…Bermekimab (MABp1) is an anti-IL-1α human monoclonal antibody [ 123 ]. Forty-two patients were enrolled in a phase 2 clinical trial, reporting that bermekimab was effectively inducing a clinical response after 12 weeks of treatment [ 123 ]. A significant reduction in abscesses and inflammatory nodules of 60% ( p < 0.004) and 46% ( p < 0.001) was seen in anti-TNF-naive and anti-TNF-failure groups, respectively.…”