Pitrakinra, a dual IL-4/IL-13 antagonist for the potential treatment of asthma and eczema

摘要

In asthma, airway inflammation is driven by Th2-related cytokines, such as IL-4, IL-5 and IL-13. IL-4 and IL-13, in particular, have a major role in the development of airway hyperresponsiveness, allergen-specific IgE synthesis and airway remodeling because of their synergistic effects induced by binding to the IL-4Rα subunit. Pitrakinra (AER-001, BAY-16-9996), being developed by Aerovance, under license from Bayer, for the potential treatment of asthma and eczema, is an IL-4 mutein, which binds to the IL-4Rα subunit and prevents the inflammation induced by IL-4 and IL-13. Pitrakinra demonstrated a potent inhibitory activity on IL-4/IL-13-mediated proliferative effects in vitro and reduced allergen-induced inflammation in animal models of asthma and skin inflammation. In phase I and II clinical trials in patients with asthma, subcutaneous and inhaled (as dry powder or nebulized) formulations of pitrakinra reduced airway inflammation, with superior effects observed with inhaled formulations. At the time of publication, a phase II clinical trial with the dry powder formulation of pitrakinra was ongoing in patients with asthma. Subcutaneous pitrakinra demonstrated preliminary efficacy results in patients with atopic eczema in a phase II clinical trial and a PEGylated variant of subcutaneous pitrakinra is being investigated for this indication. Further studies are warranted to allow a better therapeutic positioning and a more detailed characterization of the efficacy and safety of pitrakinra in asthma and atopic eczema.