Teva Pharmaceutical Industries Ltd., has presented results from a post hoc analysis of two pivotal Phase III clinical trials showing that treatment with reslizumab reduced clinical asthma exacerbations (CAEs) by 75 percent versus placebo in a subgroup of patients with late onset asthma (diagnosed at 40 years of age and older) with elevated blood eosinophils, who were inadequately controlled on inhaled corticosteroids (ICS). Reslizumab is a humanized anti-interleukin-5 (IL-5) monoclonal antibody (mAb) for which Teva is seeking approval in the treatment of asthma in patients with elevated blood eosinophils who are inadequately controlled on an ICS-based regimen. These results were presented as a late-breaking abstract at the 2015 ERS International Congress in Amsterdam.
"Asthma diagnosed after the age of 40 falls into a distinct subtype which is often very challenging to treat," commented abstract author, Professor Guy Brusselle, Ghent University Hospital, Belgium. "These latest results for reslizumab are therefore particularly encouraging, as they indicate that the drug, in combination with standard of care therapy, may provide these patients with a much-needed new option to help alleviate their symptoms and significantly improve their asthma control."
In order to determine the influence that age of asthma onset has as it relates to the efficacy of reslizumab, results were pooled from two Phase III clinical trials that investigated reslizumab IV 3 mg/kg in patients who were inadequately controlled on an ICS-based regimen, who had at least one asthma exacerbation within the previous 12 months, and a blood eosinophil count of ≥400/µL. These post-hoc analysis results indicate that, in the subgroup with late onset asthma, reslizumab showed a 75 percent reduction in asthma exacerbations and improvement in lung function as measured by forced expiratory volume in one second (FEV1). In the overall pooled patient population, asthma exacerbations were reduced by 54 percent; in the subgroup of subjects diagnosed with asthma at <40 years of age, exacerbations were reduced by 42 percent.
Data for this post-hoc analysis were pooled from two identical Phase III clinical trials (which were part of the BREATH clinical program) that comprised four placebo-controlled studies whose population of 1,700 adult and adolescent asthma patients (aged 12-75 years) had elevated blood eosinophils and symptoms that were inadequately controlled with ICS-based therapies. Common adverse events (occurring in >5 percent of patients overall) in the reslizumab treatment group were comparable to placebo and included asthma, nasopharyngitis, upper respiratory infections, sinusitis, influenza and headache. Two patients treated with reslizumab experienced anaphylactic reactions. In both cases, patients responded to standard treatment administered at the study centre. Patients were then withdrawn from participation in the study.
"Asthma is a complex disease, and some phenotypes, such as late onset asthma with elevated blood eosinophils, can present particularly significant treatment challenges that are not adequately addressed by currently available therapies," said Michael Hayden, M.D., Ph.D., President of Global R&D and Chief Scientific Officer at Teva. "Through the development of novel, targeted therapies, like reslizumab, Teva aims to provide safe and effective new treatment options to help more patients achieve improved asthma control."
Reslizumab is an investigational humanized monoclonal antibody developed to target interleukin-5 (IL-5). IL-5 is a key cytokine shown to play a crucial role in the maturation, activation and survival of eosinophils, which are a type of white blood cell that are present at elevated levels in the lungs and blood of many asthmatics. Evidence shows that eosinophils play an active role in the pathogenesis of the disease. Increased levels of eosinophils in the sputum and blood have been shown to positively correlate with disease severity and increased risk of asthma exacerbations. Reslizumab is thought to act by binding circulating IL-5 and preventing IL-5 from interacting with its receptor.