Long-Term Study Supports Safety of Asthma Drug Mepolizumab (Nucala)

Positive risk–benefit profile maintained for 52 weeks

New safety and efficacy data have shown that the risk–benefit profile generated through pivotal studies of mepolizumab (Nucala, GlaxoSmithKline) was maintained over 52 weeks. The study also demonstrated the exacerbation risk reduction, asthma control improvement, and oral corticosteroid dose reduction seen in earlier trials.

Mepolizumab is a monoclonal antibody that binds to interleukin-5 (IL-5), preventing it from binding to its receptor on the surface of eosinophils. Inhibiting IL-5 binding in this way reduces blood, tissue, and sputum eosinophil levels.

In the U.S., mepolizumab is approved as an add-on maintenance treatment for patients 12 years of age and older with severe asthma and an eosinophilic phenotype. Mepolizumab is not approved for the treatment of other eosinophilic conditions or for the relief of acute bronchospasm or status asthmaticus.

A total of 651 patients participated in the open-label COSMOS trial. Of these patients, 414 had received mepolizumab in either the 32-week, phase 3 MENSA exacerbation study or the 24-week SIRIUS steroid-reduction study, providing up to 84 weeks of on-treatment safety and efficacy data. The COSMOS study also included 237 patients who had received placebo in the previous phase 3 trials. For patients switching from placebo to mepolizumab, findings from COSMOS showed improvements in asthma control similar to those in the mepolizumab arms of the previous studies.

The primary objective of the COMSOS trial was to describe the safety profile of long-term mepolizumab treatment. The findings showed that the safety profile of mepolizumab was similar to that reported in previous phase 3 randomized studies. The most frequently reported adverse events during the treatment period were nasal congestion (30%), upper respiratory tract infection (16%), asthma exacerbation (14%), and headache (14%).

The study’s secondary objective was to evaluate the effect of long-term dosing on clinical markers of asthma control. In patients continuing with mepolizumab from the MENSA trial, exacerbation rates per year remained consistent with those of the pivotal studies. The exacerbation rates were 0.91 per year at the end of MENSA and 0.92 per year at the end of the combined 84-week treatment period. Improvements in asthma control, measured by the Asthma Control Questionnaire-5 (ACQ-5) score, seen in earlier trials were also maintained. For patients previously treated with placebo, their risk of an exacerbation was nearly halved when they switched to mepolizumab, decreasing over time from 1.94 per year to 1.04 per year, which was consistent with previous data. In addition, ACQ-5 scores improved by 0.30 points by week 4 compared with baseline, and this change was maintained to week 52 for patients previously given placebo.

A post hoc analysis evaluated the durability of steroid reduction after open-label treatment with mepolizumab in a subset of subjects from the SIRIUS study that completed the COSMOS study. The effect of mepolizumab on the oral corticosteroid dose seen in SIRIUS was consistent with that seen in COSMOS. For patients who continued treatment with mepolizumab, the median oral corticosteroid dosage was maintained at 2.5 mg/day, having been reduced from 10 mg/day at the start of the SIRIUS study. Patients switching to mepolizumab from placebo in SIRIUS demonstrated reductions in oral corticosteroid use similar to those seen in the previous trial, reducing their steroid dose by 50%––from a median dose of 10 mg/day down to 5 mg/day.

In contrast to the SIRIUS study, the COSMOS trial did not require physicians to follow an oral corticosteroid reduction protocol with a formal step-down algorithm. However, reductions in oral corticosteroid doses were achieved in the COSMOS study and were accompanied by consistent reductions in the exacerbation rate and improvements in symptom control.

Source: GlaxoSmithKline; March 5, 2016.