Asthma – reslizumab
Acute asthma attacks can require hospitalisation or even prove fatal, but in some sufferers the standard regimen does not give adequate control
Asthma is a common chronic disease, the incidence of which is rising. Typically characterised by inflammation and narrowing of the airways, its severity can vary over time. The normal symptoms of shortness of breath and a tight chest can lead to acute attacks which, in the most severe cases, can require hospitalisation and even prove fatal. It is typically managed by inhaled corticosteroids to prevent attacks, and then inhaled drugs such as salbutamol to give relief during acute exacerbations. However, in some asthma sufferers, this regimen does not give adequate control, and alternative strategies are required.
One such option is the humanised monoclonal antibody reslizumab, which is being developed by Teva for adolescent and adult patients who have elevated levels of eosinophils accompanying their poorly controlled asthma. Eosinophils are pro-inflammatory cells that are involved in allergic diseases such as asthma. Reslizumab, first developed by Ception Therapeutics, is an IL-5 neutralising agent that was shown to inhibit eosinophilia in a number of animal models, with concomitant reductions in bronchoconstriction and airway hyperactivity.1 It affects the maturation process of the eosinophils.
In one randomised, placebo-controlled study, 106 patients with poorly controlled eosinophilic asthma were given 3.0mg/kg infusions of the antibody or placebo at baseline, and again at weeks 4, 8 and 12.2 The primary efficacy measure was the difference in change to asthma control questionnaire (ACQ) score between the two groups from baseline to end of treatment at 15 weeks or early withdrawal. The mean change in ACQ score from start to end of therapy was -0.7 for the treatment group, and -0.3 in the placebo group. There was an improvement in airway function, as measured by FEV(1), for those given the antibody, compared with a slight decline with placebo. There was also a significant reduction in sputum eosinophils for treated patients. The most common side-effects were fatigue, paryngolaryngeal pain and nasopharyngitis.
Two multicentre, parallel, double blind, randomised, placebo-controlled Phase III trials have been carried out, both in patients aged 12–75 with asthma that was inadequately controlled by medium to high doses of corticosteroids, and blood eosinophil counts of at least 400 per µl.3 They were given 3.0mg/kg of the antibody intravenously or placebo every week for a year.
Across the two trials, 953 patients were enrolled, and in both cases those given reslizumab experienced a significant reduction in asthma exacerbations compared with the placebo groups. The most common adverse events were a worsening of asthma symptions, which was worse with placebo, upper respiratory tract infections and nasopharyngitis. Two given the antibody had anaphylactic reactions, which were successfully treated.
A double blind, randomised, placebo-controlled trial has also been carried out in 226 children and adolescents with the chronic allergic disease eosinophilic oesophagitis.4 Subjects were given 1, 2 or 3mg/kg of reslizumab or placebo at weeks 0, 4, 8 and 12. The median reductions in peak intraepithelial oesophageal eosinophil counts were 59, 67 and 64% respectively for the three treatment groups, and 24% for placebo. However, all patients saw improvements in the physicians’ global assessment scores, and the differences were not significant.
The most common side-effects for those given reslizumab were cough, headache, nasal congestion and infections of the upper respiratory tract.
References1. G.M. Walsh et al. Curr. Opin. Mol. Ther. 2009, 11, 329
2. M. Castro et al. Am. J. Respir. Crit. Care Med. 2011, 184, 1125
3. M. Castro et al. Lancet Respir. Med. 2015, 3, 35
4. J.M. Spergel et al. J. Allergy Clin. Immunol. 2012, 129, 456