Atopic dermatitis (AD) is an inflammatory skin disease affecting as much as 20% of the population in western industrial societies. Chronic eczema in AD and associated pruritus can be a significant cause of morbidity and impact life quality. Disease pathogenesis is complex but ultimately converges on a pathological inflammatory process that disrupts the protective barrier function of the skin.
The prototypical inflammatory cytokine IL-1⍺ plays a key role in the pathophysiology of a wide range of inflammatory skin disorders1. MABp1 (bermekimab) is a natural human antibody that exhibits immunoregulatory activity through blocking IL-1⍺ activity. Keratinocytes are a major reservoir of IL-1⍺ and may be a key source of inflammatory stimulus in AD. IL-1⍺ is present on leukocytes, where its role in leukocyte trafficking and infiltration may represent a key step in the chronic inflammation of AD. IL-1⍺ is a key inducer of matrix metalloproteinases activity which could be directly involved in the epithelial barrier breakdown in AD2. Loss of regulation of IL-1 results in systemic inflammation with extensive skin involvement3.
In previous dermatology studies bermekimab was well tolerated and showed impressive therapeutic activity4,5,6. Dose ranging of the subcutaneous formulation of bermekimab is now being studied in an open label treatment regimen for AD in order to establish the basis for further potential randomized studies.
XBiotech recently announced launch of a Phase 2, open label clinical trial to evaluate bermekimab in patients with moderate to severe Atopic Dermatitis (AD). The Company will be introducing its new pre-filled syringes to deliver bermekimab by subcutaneous injection. The Company has just released its first production lot of pre-filled syringes which contain a highly concentrated formulation of bermekimab, allowing dosing of 400mg in a single, convenient injection. The study will test the subcutaneous bermekimab therapy in AD patients after only 4 or 8 weeks of treatment, compared with the 16 week treatment regimen currently used for the only approved antibody therapy for AD. Longer treatment durations may be needed to achieve optimal clinical activity with bermekimab, particularly when there are severe skin lesions. Evaluating the subcutaneous dose, rapidity, and extent of response is the purpose of the study. Findings from the AD study could establish the basis for further randomized studies that would be necessary for the purpose of product registration.
You can find more information on this study by visiting www.clinicaltrials.gov
Bou-Dargham MJ et al. The Role of Interleukin-1 in Inflammatory and Malignant Human Skin Diseases and the Rationale for Targeting Interleukin-1 Alpha. Med Res Rev. 2017 Jan;37(1):180-216.
Han et al. Interleukin-1alpha-induced proteolytic activation of metalloproteinase-9 by human skin. Surgery. 2005 Nov;138(5):932-9.
Askentijevich et al. An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist. N Engl J Med. 2009 Jun 4;360(23):2426-37.
Kanni T et al. MABp1 Targeting Interleukin-1Alpha for Moderate to Severe Hidradenitis Suppurativa not Eligible for Adalimumab: A Randomized Study. J Invest Dermatol. 2017 Nov 9.
Coleman KM et al. Open-Label Trial of MABp1, a True Human Monoclonal Antibody Targeting Interleukin 1α, for the Treatment of Psoriasis. JAMA Dermatol. 2015 May;151(5):555-6.
Carrasco D et al. An Open Label, Phase 2 Study of MABp1 Monotherapy for the Treatment of Acne Vulgaris and Psychiatric Comorbidity. J Drugs Dermatol. 2015 Jun;14(6):560-4.