Clinical Trials

Date: 2017-05-22

Type of information: Presentation of results at a congress

phase: 3b

Announcement: presentation of results at the American Thoracic Society (ATS) conference

Company: GSK (UK)

Product: Nucala® (mepolizumab)

Action mechanism:

• monoclonal antibody. Mepolizumab is a fully humanised IgG monoclonal antibody specific for interleukin 5 (IL-5). IL-5 is a cytokine which regulates the growth, activation and survival of eosinophils and provides an essential signal for the movement of eosinophils from the bone marrow into the lung. Mepolizumab binds to human IL-5, stopping it from binding to its receptor on the surface of eosinophils. Inhibiting IL-5 binding in this manner reduces blood, tissue and sputum eosinophil levels, which in turn reduces the frequency of exacerbations.

Disease: asthma

Therapeutic area: Inflammatory diseases - Respiratory diseases

Country: Argentina,Belgium,Bulgaria,Canada,Czechia,Estonia,France,Germany,Greece,Italy,Netherlands,Norway,Peru,Russian Federation, Slovakia, Spain, Ukraine, UK, USA

Trial details:

• The MUSCA study (Mepolizumab adjUnctive therapy in subjects with Severe eosinophiliC Asthma) involved 551 patients treated with Nucala 100mg subcutaneous injection, every 4 weeks for a 24 week period. The MUSCA study is the first clinical trial designed primarily to assess the effect of mepolizumab on disease-specific health-related quality of life using the St George’s Respiratory Questionnaire (SGRQ) in patients with severe asthma with an eosinophilic phenotype. Using a series of questions that patients complete themselves, the SGRQ looks at how a patient’s asthma symptoms impact on everyday activities, such as walking, housework, going to the shops, gardening or light exercise, and whether their severe asthma prevents them from doing activities they might otherwise expect to do. (NCT02281318)
• The MUSCA study (Mepolizumab adjUnctive therapy in subjects with Severe eosinophiliC Asthma) involved 551 patients treated with Nucala 100mg subcutaneous injection, every 4 weeks for a 24 week period. The MUSCA study is the first clinical trial designed primarily to assess the effect of mepolizumab on disease-specific health-related quality of life using the St George’s Respiratory Questionnaire (SGRQ) as a primary endpoint in patients with severe asthma with an eosinophilic phenotype.

Latest news:

• • On May 22, 2017, GSK presented data from a post-hoc analysis of the phase IIIb MUSCA study in which first-in-class biologic Nucala (mepolizumab) consistently improved health-related quality of life and lung function in patients with severe asthma across blood eosinophil levels of 150 cells/µL and above. The data also showed an association between increasing lung function improvement and increasing eosinophil levels.
• The analysis presented at the American Thoracic Society (ATS) conference, Washington DC, US, looked at treatment response at week 24 in patients treated with mepolizumab compared to placebo, both added to standard of care (high dose inhaled corticosteroids plus at least one additional controller). The data showed that for patients in the mepolizumab arm:
• - Quality of life, as measured by St. George’s Respiratory Questionnaire (SGRQ) score, improved by 7.8 units (95% CI: -11.0, -4.7), 8.2 units (95% CI: -12.2, -4.2) and 7.7 units (95% CI: -13.3, -2.1) versus placebo in patients with blood eosinophils of ?150, ?300 and ?500 cells/mL respectively – improvements were approximately double the defined clinically meaningful difference of 4.0 units at each of the three blood eosinophil thresholds
• - Lung function, as measured by pre-bronchodilator FEV1, increased by 137mL (95% CI: 56, 218), 165mL (95% CI: 64, 265) and 206mL (95% CI: 77, 335) versus placebo in patients with blood eosinophils of ?150, ?300 and ?500 cells/mL respectively – all improvements were clinically relevant.
• The post-hoc analysis also examined exacerbation rate and asthma control by eosinophil threshold, both of which improved in mepolizumab-treated patients in line with findings from previous studies. In addition to providing further data on these endpoints, the findings of the post-hoc analysis reinforce prior studies demonstrating the utility of a blood eosinophil threshold of ?150 cells/µL for the identification of patients with severe asthma and frequent exacerbations, despite high-dose ICS plus other controller(s), likely to benefit from treatment with mepolizumab.
• This post-hoc analysis specifically looked at changes to quality of life (measured by SGRQ score) and lung function (measured by FEV1), as well as asthma control (measured by ACQ-5 score) and annualised rate of exacerbations in patients stratified by baseline eosinophil level (<150, ?150, ?300, or ?500 cells/mL) who were treated with mepolizumab added to standard of care, when compared to patients treated with placebo and standard of care (high dose inhaled corticosteroids plus at least one additional controller).
• The post-hoc analysis did not specifically assess safety. However, safety was assessed in the MUSCA study and the safety profile of mepolizumab was consistent with the product label for Nucala.
• • On March 6, 2017, GSK announced data demonstrating that severe asthma patients, whose disease is driven by eosinophilic inflammation, treated with Nucala® (mepolizumab) added-on to standard of care, achieved clinically and statistically significant improvements in their health-related quality of life and lung function, when compared to patients treated with placebo and standard of care.
• Results of the MUSCA study presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting, showed in patients treated with mepolizumab as an add on to standard care:
• Georges Respiratory Questionnaire (SGRQ) score (primary endpoint), a measure of quality of life, improved by 7.7 units from baseline vs. placebo after 24 weeks – nearly double the defined clinically meaningful difference of ?4.0 units. Lung function (first secondary endpoint), as measured by pre-bronchodilator FEV1, increased by 120mL more than in placebo patients at week 24 – a clinically relevant and statistically significant improvement.
• FEV1 and SGRQ scores were also measured during the study, with improvements seen at the first measurement interval, after the first four weeks and sustained throughout the 24-week trial.
• Asthma control, as measured by the Asthma Control Questionnaire-5 (ACQ-5) (additional secondary endpoint), showed a significant improvement vs. placebo in the mepolizumab treatment group by 0.40 units .
• Exploratory endpoints were the annual rate of exacerbations (asthma attacks), which was reduced by 58%, and the number of exacerbations requiring emergency room visits or hospitalisation, which was reduced by 68% for people treated with mepolizumab compared with placebo. These results were comparable to those seen in the pivotal phase III MENSA study. Safety was also assessed and the safety profile of mepolizumab in the MUSCA study was consistent with the product label for Nucala®.

Is general: Yes