Reslizumab, a humanized anti-IL-5 mAb for the treatment of eosinophil-mediated inflammatory conditions.

Eosinophils are pro-inflammatory cells that make a major contribution to allergic diseases affecting the upper and lower airways, skin and gastrointestinal tract. IL-5 is central to eosinophil maturation and release from the bone marrow, and to the subsequent accumulation, activation and persistence of eosinophils in the tissues. Reslizumab from Ception Therapeutics Inc is a humanized mAb with potent IL-5-neutralizing effects. The agent inhibited eosinophilia in several animal models; reductions in airway hyperactivity and bronchoconstriction were also observed. Clinical trials for reslizumab have been completed in a small number of patients with asthma, nasal polyposis, hypereosinophilic syndrome (HES) and eosinophil gastroenteritis (EG). Eosinophil depletion was observed in all trials, but clinical responses were often limited, particularly in patients with asthma; furthermore, some patients exhibited rebound of disease to levels greater than baseline. At the time of publication, phase II/III and phase III trials were ongoing in patients with eosinophilic esophagitis (EE), and a phase II trial was ongoing in patients with asthma. Reslizumab is a potentially efficacious and well-tolerated treatment for EG, EE, HES and eosinophilic polyposis, although more trials are required to understand the underlying mechanism of disease rebound. However, the rarity of conditions such as HES, EE and EG makes the conduct of such trials difficult.