FDA Approves GSK's Nucala as First Biologic Therapy for Hypereosinophilic Syndrome

Compiled by Keke

On September 25, GSK announced that the U.S. FDA had approved Nucala (mepolizumab) for the treatment of hypereosinophilic syndrome (HES) in adult and pediatric patients aged 12 years and older with persistent eosinophilia lasting ≥6 months and no identifiable non-hematologic secondary cause. This approval makes Nucala the first and only biologic therapy approved in the United States for patients with eosinophil-driven diseases.

The U.S. FDA’s approval of Nucala was based on a priority review of data from a clinical development program, which included positive results from a pivotal Phase 3 clinical study recently published in The Journal of Allergy and Clinical Immunology. This 32-week, randomized, double-blind, placebo-controlled pivotal study enrolled a total of 108 patients and aimed to evaluate the efficacy and safety of subcutaneous mepolizumab 300 mg (3x100 mg) administered every four weeks versus placebo in patients aged 12 years and older with uncontrolled hypereosinophilic syndrome (HES). Uncontrolled HES was defined as having experienced at least two HES flares (worsening of symptoms or an increase in eosinophil count requiring treatment) within the past 12 months, and a blood eosinophil count of ≥1,000 cells/µL at screening.

The primary endpoint was the proportion of patients experiencing one HES flare during the 32-week treatment period. Secondary endpoints included time to first HES flare (defined as the time from randomization to the occurrence of an HES flare), the proportion of patients experiencing one HES flare during weeks 20–32 of treatment, the annualized rate of HES flares, and the change from baseline in fatigue severity assessed by item 3 of the Brief Fatigue Inventory (BFI).

The study showed that, over a 32-week period, mepolizumab treatment reduced the proportion of patients experiencing HES flares (worsening of symptoms or an eosinophil threshold requiring treatment escalation) by 50% compared with placebo (28% vs. 56%; p=0.002), thereby meeting the primary endpoint. Furthermore, compared with the placebo group, mepolizumab treatment was associated with a 66% reduction in the risk of first HES flare (hazard ratio [HR]=0.34, 95% CI: 0.18–0.67), a 66% reduction in the annualized rate of HES flares (rate ratio [RR]=0.34, 95% CI: 0.19–0.63), and improvement in fatigue scores (p=0.036), indicating statistical significance for the secondary endpoints. The safety results in this study were consistent with the known safety profile of Nucala.

Nucala was first approved in 2015 for the treatment of severe eosinophilic asthma (SEA) and is the first monoclonal antibody targeting IL-5. It is believed that the drug prevents IL-5 from binding to receptors on the surface of eosinophils, thereby reducing blood eosinophil levels to normal. At normal levels, eosinophils may play a role in maintaining health.

Mepolizumab has been developed for the treatment of diseases driven by eosinophil-mediated inflammation. The drug has been studied in more than 3,000 patients across 26 clinical trials covering 26 eosinophil-related indications, and has been approved under the brand name Nucala in the United States, Europe, and more than 20 other markets as add-on maintenance therapy for severe eosinophilic asthma (SEA) and eosinophilic granulomatosis with polyangiitis (EGPA). Regulatory applications for mepolizumab in the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) are expected to advance in 2020. Mepolizumab is currently also being investigated in chronic obstructive pulmonary disease (COPD) and has not been approved for the relief of acute bronchospasm or status asthmaticus.

Reference:

1.FDA approves Nucala as the first and only biologic treatment for Hypereosinophilic Syndrome (HES)

2.Nucala (mepolizumab) is the first treatment to show a significant reduction in flares for patients with Hypereosinophilic Syndrome (HES)