NUCALA (mepolizumab) a humanized, interleukin-5 (IL-5) antagonist monoclonal antibody approved for adult and pediatric patients aged 6 years and older with severe asthma and with an eosinophilic phenotype, adult patients 18 years and older with chronic rhinosinusitis with nasal polyps, adult patients with eosinophilic granulomatosis with polyangiitis (EGPA), and adult and pediatric patients aged 12 years and older with hypereosinophilic syndrome for ≥6 months without an identifiable non-hematologic secondary cause. 

1. Long-Term Safety and Efficacy of Mepolizumab in Japanese Patients with Eosinophilic Granulomatosis with Polyangiitis (Abstract #POS0298)

Mepolizumab demonstrates long-term safety and efficacy in patients with EGPA over a mean treatment duration of 4.2 years. Of the 118 enrolled patients, 91% completed the study, and 58% reported adverse events (AEs), primarily infections. Serious AEs occurred in 22% of patients, but none were drug-related. The treatment resulted in significant reductions in oral corticosteroid (OCS) use, with 36% of patients becoming OCS-free by the study's end. Clinical symptoms and EGPA relapses decreased, and the annualized rate of EGPA-related hospitalizations and emergency visits significantly dropped. These findings underscore mepolizumab's potential as an effective long-term therapy for EGPA.

2. Long-Term Efficacy of Mepolizumab in Patients with Eosinophilic Granulomatosis with Polyangiitis: A Multicenter Propensity Score Matching Analysis (Abstract # POS0308)

Propensity score matching (PSM) analysis revealed that the 5-year survival rate was significantly higher in the mepolizumab group compared to the non-mepolizumab group (100% vs. 86.5%). Additionally, the mepolizumab group exhibited lower Birmingham Vasculitis Activity Scores (BVAS) and reduced glucocorticoid (doses at the last observation (median: 4mg/day vs. 5mg/day), with a higher proportion achieving a glucocorticoid dose of ≤ 4mg/day (51.4% vs. 24.2%). Multivariate logistic regression analysis indicated that mepolizumab administration was positively associated with achieving a glucocorticoid dose of ≤ 4mg/day (OR 3.55, 95% CI=1.15–11.0) and inversely associated with wheeze at disease onset (OR 0.103, 95% CI=0.0197–0.544). These findings suggest that mepolizumab effectively controls disease activity, reduces GC dependency, and enhances long-term survival in EGPA patients.

Conclusion:

As per DelveInsight, about 73,000 cases of ANCA-associated vasculitis were present in the US in 2023, and EGPA accounted for up to 17% of cases. 

According to GlaxoSmithKline, NUCALA generated WW sales of ~USD 1,790 million in 2023, and the US accounted for up to 60% of the total sales. According to DelveInsight, NUCALA captured USD 275 million in sales from ANCA-associated vasculitis in the US. The company expects a regulatory decision for chronic rhinosinusitis with a nasal polyp and chronic obstructive pulmonary disease in Japan and the US, respectively, in H2 2024. 

 

The recent findings on mepolizumab's long-term efficacy and safety provide a promising outlook for patients with EGPA. The reduction in oral corticosteroid use and improvement in clinical outcomes underscore the potential of mepolizumab as a cornerstone therapy for EGPA. Notably, the significant increase in 5-year survival rates and the lower disease activity scores in the mepolizumab group highlight its effectiveness in controlling the disease and reducing dependency on glucocorticoids. These results are particularly encouraging, given the chronic nature of EGPA and the associated risks of long-term steroid use. The consistent safety profile, with no drug-related serious adverse events, further reinforces mepolizumab's suitability for long-term management of this condition. As more data become available, mepolizumab could become an essential component of EGPA treatment regimens, offering patients a viable path to improved quality of life and disease control. There is, however, a high unmet need for the treatment of ANCA-associated vasculitis; a proportion of patients are refractory to current therapies.