Mepolizumab is an anti-interleukin-5 monoclonal antibody that is in clinical 
trials with GlaxoSmithKline (GSK) for the treatment of severe asthma, nasal 
polyposis and hypereosinophilic syndrome and eosinophilic oesophagitis (the 
latter two indications are classed as eosinophilia in the phase table). 
Interleukin-5 stimulates the production, activation and maturation of 
eosinophils. Since mepolizumab inhibits interleukin-5 and has a long terminal 
half-life, treatment with mepolizumab causes a sustained reduction in the 
numbers of circulating eosinophils. Thus, mepolizumab may be a useful 
therapeutic agent for the treatment of conditions characterized by increased 
levels of eosinophils. Hypereosinophilic syndrome is a rare idiopathic disease 
with broad clinical signs and symptoms that is diagnosed based on a persistent 
blood eosinophil count of >1500 cells, various end-organ damages (including 
skin, heart, lung, nervous system and digestive system), and with exclusion of 
known secondary causes of hypereosinophilia. Mepolizumab is in clinical trials 
for the treatment of hypereosinophilic syndrome, eosinophilc oesophagitis, 
severe asthma (in patients with airway eosinophilia) and nasal polyposis. 
GlaxoSmithKline (GSK) has completed enrolment in a phase II study of mepolizumab 
in 20 patients with symptomatic eosinophilic bronchitis with or without asthma 
in Canada. The randomized, double-blind, placebo-controlled study is evaluating 
the effects of intravenous mepolizumab on asthma control, airway eosinophilia 
and the degree to which concomitant corticosteroid treatment can be reduced 
(NCT00292877). In previous clinical studies, including trials in the EU and US, 
mepolizumab has shown a lack of effect on allergen-induced airway responses and 
inflammation despite a significant reduction in blood and sputum eosinophil 
levels.A randomized, double-blind, placebo-controlled, multicentre, phase III 
study of mepolizumab over 9 months in 85 patients with hypereosinophilic 
syndrome was completed in 2006. All patients have been offered, and continued 
in, a phase III, open-label, long-term extension study of mepolizumab. Enrolment 
in this study was completed in September 2006.A phase III, compassionate use 
trial of mepalizumab (NCT00244686) in patients with hypereosinophilic syndrome 
was ongoing in October 2007 in the US. Patients who have significant clinical 
disease but are unresponsive to traditional treatment and those who have 
demonstrated clinical benefit from previous anti-IL-5 treatment are eligible to 
take part in the trial. Mepolizumab received orphan drug status for first-line 
treatment in patients with hypereosinophilic syndrome in the US and the EU in 
2004. Mepolizumab is also in phase I/II clinical development for the treatment 
of eosinophilic oesophagitis. A phase I/II trial (NCT00358449) began in August 
2006 in the US, Australia, the UK and Canada, and will enrol approximately 72 
paediatric patients with eosinophilic oesophagitis. The randomized, 
parallel-group clinical trial will evaluate the safety, tolerability, 
pharmacokinetics and pharmacodynamics of intravenous mepolizumab for 12 weeks. 
In September 2006, GSK completed enrolment in a phase I/II study of mepolizumab 
for the treatment of eosinophilic oesophagitis in ten adult patients in 
Switzerland (NCT00274703). The randomized, double-blind, placebo-controlled 
study will evaluate the pharmacokinetics, pharmacodynamics, safety and 
tolerability of IV mepolizumab.A phase I/II trial of mepolizumab in four 
patients with eosinophilic oesophagitis conducted by Cincinnati Children's 
hospital found the monoclonal antibody was safe and effective. Brigham and 
Women's Hospital in association with GSK is conducting a phase I/II trial of 
mepolizumab in patients with Churg-Strauss Syndrome (CSS) in the US. The trial, 
which started in September 2007, will evaluate the potential of mepolizumab to 
reduce the need for corticosteroid therapy in patients with CSS (NCT00527566). 
CSS, otherwise known as allergic granulomatosis, is defined by patients with 
asthma, eosinophilia and vasculitis.