GSK phase lll study of mepolizumab meets co-primary & all secondary endpoints in patients with EGPA

• A key goal of treatment for EGPA is to induce and maintain remission while reducing the use of corticosteroids and other immunosuppressive therapies. The co-primary endpoints for this 52-week study assessed the total duration of remission and the proportion of patients that achieved sustained remission following treatment with mepolizumab compared to treatment with placebo, both on top of standard of care. Remission for these two endpoints was defined by a Birmingham Vasculitis Activity Score (BVAS), a scoring system to assess disease activity, of 0 and corticosteroid dose <4mg/day prednisolone/prednisone.
• The difference between the two treatment groups was statistically significant for both co-primary endpoints as defined, respectively, by: The duration of remission as defined by the proportion of patients achieving at least 24 weeks duration of remission, one of five pre-defined categories of duration, was 19/68 (28%) for mepolizumab and 2/68 (3%) for placebo (P<0.001); The proportion of patients achieving remission at both weeks 36 and 48 of the study treatment period. This was 22/68 (32%) for mepolizumab and 2/68 (3%) for placebo (P<0.001).
• The study included six secondary endpoints investigating relapse, remission and corticosteroid use, all considered clinically relevant for patients with EGPA. Patients demonstrated statistically significant differences, in favour of mepolizumab, for all secondary endpoints compared to placebo.
• Steve Yancey, vice president and medicine development lead for mepolizumab, GSK said: “We are very pleased to observe the positive benefits of treatment with mepolizumab across several clinically relevant measures in this first ever double-blind, placebo-controlled study in patients with Eosinophilic Granulomatosis with Polyangiitis. Given that patients with this rare systemic inflammatory disease have limited treatment options, these results represent a significant step forward in our efforts to help them.  We now look forward to progressing our regulatory submission plans.”
• Most frequent on-treatment serious adverse events reported for mepolizumab and placebo, respectively were asthma (4%, 4%), influenza (0, 3%) and pneumonia (0, 3%). One death was reported in a patient receiving mepolizumab which was not considered by the investigator to be related to study treatment.
• Mepolizumab is a humanised IgG monoclonal antibody specific for interleukin 5 (IL-5). It is one of the ~40 assets profiled to investors at GSK’s R&D event in November 2015 and belongs to the company’s respiratory portfolio - one of six core areas of scientific research and development alongside immuno-inflammation, oncology, vaccines and infectious and rare diseases.
• IL-5 is a cytokine which regulates the growth, activation and survival of eosinophils (white blood cells) and provides an essential signal for the movement of eosinophils from the bone marrow into the lung and other organs.  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 eosinophil-mediated inflammation.
• Mepolizumab is not approved for use anywhere in the world for EGPA.
• It is approved for use in the EU, under the brand name Nucala, for use as an add-on treatment for severe refractory eosinophilic asthma in adult patients.
• Nucala is approved for use in the US as an add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype. It is not approved for the treatment of other eosinophilic conditions or relief of acute bronchospasm or status asthmaticus.
• Nucala has also been approved in Canada, Australia, Japan, Switzerland, Chile, South Korea and Taiwan.
• Nucala is a registered trade mark of the GSK group of companies.

Gsk phase lll, mepolizumab meets co-primary, secondary endpoints, patients with egpa