GlaxoSmithKline plc presented positive results from the OSMO study at the American Academy of Allergy, Asthma & Immunology (AAAAI) and World Allergy Organization (WAO) Joint Congress in Orlando. The results showed that severe asthma patients who are uncontrolled despite receiving Xolair (omalizumab) and who are eligible for treatment with Nucala (mepolizumab), experience improved asthma control when switched on to mepolizumab.   

OSMO is an open-label, single-arm study which investigated whether patients who had been receiving omalizumab, (a biologic targeting IgE in patients with allergic sensitisation) for an average of 2.5 years and continued to have uncontrolled severe asthma, gained better asthma control following a switch to mepolizumab, (a biologic targeting IL-5 for patients with severe eosinophilic asthma). In the study 145 patients, who were documented to have experienced at least two asthma exacerbations in the year prior to enrolment, were switched directly to mepolizumab without a wash-out period and followed for 32 weeks.

In this study, mepolizumab data compared with baseline values prior to first dose, unless otherwise stated: Met the primary endpoint of asthma control with clinically significant improvements, as evaluated by the Asthma Control Questionnaire (ACQ-5), with a mean change from baseline of -1.45 at week 32; Met all secondary endpoints and other key endpoints; Rate of exacerbations requiring oral steroids reduced by 64% vs prior 12 months (3.26 to 1.18); Rate of exacerbations requiring an ED visit or hospitalization reduced by 69% vs prior 12 months (0.63 to 0.19); Improvement in lung function (pre-bronchodilator FEV1) of 159 mL vs baseline; Improvement in Quality of life as evaluated by the SGRQ (-19 units, compared with MCID -4.0) vs baseline; Reduction in blood eosinophils of approximately 80% by Week 4 (vs baseline), which was sustained until Week 32;  Safety profile was consistent with the known profile of the treatment.

Ken Chapman, Professor of Medicine, University of Toronto and an investigator in the OSMO study said: “Patients participating in this study suffered burdensome day to day asthma symptoms and frequently required access to urgent care when their asthma symptoms significantly worsened. Like many similar patients, they had both eosinophilic and allergic characteristics, making them eligible to receive treatment with either omalizumab or mepolizumab. OSMO showed us that when these patients remained uncontrolled on omalizumab and were then switched to mepolizumab, they experienced significant improvements - fewer symptoms, better lung function, improved asthma-related quality of life and fewer exacerbations. This study is a valuable addition to our understanding of how to manage patients with biologic therapies.”

In a further abstract/poster presented at AAAAI/WAO Joint Congress, a pooled, post-hoc meta-analysis of data from the MENSA and MUSCA studies, mepolizumab showed improvements in lung function of patients with severe eosinophilic asthma, measured by morning peak expiratory flow (AM PEF), compared with placebo. Early improvements were seen in week one and sustained at the end of the observational period: the mean change in AM PEF at week one was 10 L/min in the mepolizumab group compared with 2L/min in the placebo group and at the end of the observational period the mean change in AM PEF was 26 L/min in the mepolizumab group compared to 4 L/min in the placebo group. This improvement was shown to be greater at higher eosinophil counts.

Jonathan Sweeting, SVP and Head, Global Respiratory Franchise, GSK said: “It is important to have evidence to support decisions on prescribing the right treatment to the right severe asthma patient. There is existing data that supports the use of mepolizumab in patients with severe eosinophilic asthma; with OSMO we wanted to understand how to manage the more complex patients who are eligible to be treated with omalizumab or mepolizumab. The results presented today provide evidence that supports the use of mepolizumab in those eligible patients who are not well controlled by omalizumab. In addition, the meta-analysis we are presenting, which showed Nucala provides an early improvement, sustained over time in lung function compared with placebo, is further evidence supporting the effectiveness of this treatment in patients with severe eosinophilic asthma.”

OSMO was an international, open-label, single arm trial.  It enrolled patients aged 12 and older with severe eosinophilic asthma who were receiving omalizumab, but were not optimally controlled, based on Asthma Control Questionnaire score of >1.5 at screening and baseline and who experienced > 2 exacerbations in the past 12 months. The Asthma Control Questionnaire (ACQ-5) is a validated, self-administered tool, used by physicians to assess asthma control and changes in asthma control. Patients also required a peripheral eosinophil blood count of =150 cells/µL at study start or =300 cells/µL in the past 12 months to be eligible for mepolizumab.
About the meta-analysis

A post-hoc meta-analysis of data from two randomised, double-blind, placebo-controlled studies (MENSA and MUSCA) of 4-weekly sub-cutaneous mepolizumab 100 mg (n=454) versus placebo (n=456) in patients with severe eosinophilic asthma. All patients received high dose ICS plus =1 controller medication, had =2 exacerbations in the previous year and blood eosinophils =150 cells/µL at screening or =300 cells/µL in the previous year. The analysis assessed the effect of mepolizumab on AM PEF based on study entry criteria and by eosinophil thresholds. Data were analysed using a mixed model repeated measures controlling for multiple covariates.

Nucala is a market leading biologic treatment for patients with severe asthma whose symptoms are driven by inflammation linked to higher-than-normal eosinophils (a type of white blood cell) being present in the blood. When present in the body in normal levels, eosinophils can play a role in protecting the body against infection but over-production can cause inflammation in vital organs and tissues, sometimes permanently damaging them.

When inflammation occurs in the lungs it can affect the airways, making breathing difficult and increasing the frequency of exacerbations or asthma attacks. Although the mechanism of action has not been definitively established, Nucala is believed to work by preventing the ‘IL-5’ cytokine from binding to its receptor on the surface of eosinophil cells, which in turn reduces eosinophil levels. The clinical trial programme to date has shown that Nucala consistently reduced exacerbations, improved patient’s quality of life and maintains long term reduction of oral steroid dose.

Mepolizumab has been studied in over 3,000 patients in 16 clinical trials across a number of eosinophilic conditions, and is currently being investigated for severe hypereosinophilic syndrome and nasal polyposis.

Nucala 100mg is approved for the use as an add-on treatment of patients with severe eosinophilic asthma in over 40 countries including the EU, US, and Japan and has been prescribed to over 18,000 patients in the US.  Mepolizumab 300mg is now approved in the US for the treatment of adult patients with a rare disease called eosinophilic granulomatosis with polyangiitis (EGPA). An sBLA has also been filed for the treatment in patients with chronic obstructive pulmonary disease (COPD).

In the US, Nucala (100mg fixed dose subcutaneous injection of mepolizumab) is licensed as an add-on maintenance treatment for patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype. Nucala (3x 100mg subcutaneous injection of mepolizumab) is licensed for the treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA). Nucala is not approved for the relief of acute bronchospasm or status asthmaticus. Full US Prescribing Information is available at US Prescribing Information Nucala.

In the EU, Nucala (100mg fixed dose subcutaneous injection of mepolizumab) is licensed as an add-on treatment for severe refractory eosinophilic asthma in adult patients.