GSK’s Nucala (Mepolizumab) Receives FDA Acceptance for Fourth Indication in Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)

December 10, 2020 News /BioValleyBIOON/ ---GlaxoSmithKline(GSK) recently announced that the U.S. Food and Drug Administration (FDA) has accepted a supplemental Biologics License Application (sBLA) for the anti-inflammatory drug Nucala (mepolizumab) for the treatment of patients with chronic rhinosinusitis with nasal polyps (CRSwNP).

If approved, Nucala will become the first anti-IL-5 biologic approved in the United States for the treatment of CRSwNP, and the only therapy approved for four eosinophil-driven diseases. Previously, Nucala had been approved for three indications: (1) treatment of severe eosinophilicAsthma(SAE) patients; (2) treating patients with eosinophilic granulomatosis with polyangiitis (EGPA); (3) treating patients with hypereosinophilic syndrome (HES).

Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is a chronic upper respiratory disease primarily driven by type 2 inflammation, characterized by polyps that obstruct the sinuses and nasal passages. Current treatment options include intranasal corticosteroids, systemic corticosteroids, and surgery; however, all these modalities are associated with suboptimal efficacy and/or high recurrence rates. Patients may experience severe nasal obstruction, difficulty breathing, rhinorrhea, reduced or lost sense of smell and taste, and facial pain or pressure. The persistent symptoms of CRSwNP significantly adversely affect patients' health-related quality of life, including reduced productivity and ability to perform activities of daily living, inability to enjoy food, sleep deprivation, and fatigue.

Currently, in the treatment of CRSwNP, Sanofi/Regeneron’s anti-inflammatory drug Dupixent (dupilumab, an IL-4/IL-13-targeting monoclonal antibody) was approved in the United States and the European Union in June and October 2019, respectively, becoming the first biologic agent for the treatment of CRSwNP. In August and December this year,Novartis/Roche’s Xolair (Chinese brand name: Zhuole; generic name: omalizumab) has received approval in the European Union and the United States for a new indication: as an add-on therapy to intranasal corticosteroids (INC) for the treatment of adult patients (≥18 years) with severe chronic rhinosinusitis with nasal polyps (CRSwNP) whose disease is not adequately controlled with INC. This approval makes Xolair the first biologic specifically targeting and blocking immunoglobulin E (IgE) for the treatment of nasal polyps.

Nasal Polyps (Image source: myhealthandwellnessinfo.com)

If approved, Nucala will compete with Dupixent and Xolair. The regulatory submission for Nucala is based on positive results from the pivotal Phase III SYNAPSE study. This marks the first time an anti-IL-5 biologic has reported positive Phase III data in the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP), expanding the range of eosinophil-driven diseases for which Nucala has demonstrated efficacy.

Notably, all patients enrolled in the SYNAPSE study had a history of prior surgery (approximately one-third had undergone more than three surgeries) and required further surgical intervention due to severe symptoms and enlarged polyps. This study is the first clinical trial to evaluate the therapeutic benefits of biologics in this severely affected patient population.

SYNAPSE was a 52-week, randomized, double-blind, parallel-group Phase III study that enrolled more than 400 adult patients with recurrent severe bilateral nasal polyps to evaluate the efficacy and safety of Nucala versus placebo, each administered in combination with standard of care (SoC). In this study, patients were randomized to receive either Nucala (100 mg liquid formulation) or placebo, alongside SoC. Both Nucala and placebo were administered via subcutaneous injection using pre-filled syringes once every 4 weeks for 52 weeks. Patients with severe bilateral nasal polyps were defined as those with a mean visual analog scale (VAS) score for nasal congestion >5, an endoscopic score of at least 5 (on a scale up to 8), and a minimum score of 2 in each nasal cavity. Patients were required to have undergone at least one nasal polyp surgery in the past 10 years, experienced recurrent nasal polyps despite receiving standard of care, and currently required nasal polyp surgery.

The results demonstrated that the study met both co-primary endpoints: compared with the SoC + placebo group, the SoC + Nucala treatment group showed statistically significant improvements in nasal polyp volume at Week 52 (p < 0.001) and in nasal congestion during Weeks 49–52 (p < 0.001). Specifically: (1) the median difference from baseline in the total endoscopic nasal polyp score was −0.73 (95% CI: −1.11, −0.34); and (2) the median difference from baseline in the Visual Analog Scale (VAS) score for nasal congestion was −3.14 (95% CI: −4.09, −2.18). Regarding key secondary endpoints, the time to first actual nasal surgery over the 52-week period also differed significantly; compared with the SoC + placebo group, the SoC + Nucala group experienced a 57% delay in time to first actual nasal surgery (p = 0.003; 95% CI: 0.43 [0.25, 0.76]). The safety profile observed in the study was consistent with the known safety characteristics of Nucala.

Nucala was first approved in late 2015 for the treatment of severe eosinophiliaAsthma(SEA) is the first globally marketed biologic therapy targeting IL-5. The active pharmaceutical ingredient in Nucala, mepolizumab, is a monoclonal antibody that specifically targets interleukin-5 (IL-5). IL-5 is a cytokine that regulates the growth, activation, and survival of eosinophils (a type of white blood cell) and provides critical signals for their migration from the bone marrow to the lungs and other organs. Nucala binds to human IL-5, thereby blocking its interaction with receptors on the surface of eosinophils. By inhibiting this binding, Nucala reduces eosinophil levels in the blood, tissues, and sputum, which in turn diminishes eosinophil-mediated inflammation.

Based on the aforementioned mechanism of action, Nucala is being developed for the treatment of various diseases caused by eosinophil-mediated inflammation. The drug has already been approved in 21Clinical Trial, evaluated in over 3,000 patients across multiple eosinophilic indications.

To date, Nucala has been approved in the United States, Europe, and 20 other markets as an add-on maintenance treatment for adult patients with severe eosinophilic asthma (SAE). In the United States, the European Union, and several other markets, Nucala is also approved for the treatment of severe eosinophilic asthma in children aged 6 to 17 years.Asthma(SAE) pediatric patients. Furthermore, Nucala has been approved in multiple markets, including the United States, Japan, and Canada, as an add-on maintenance therapy for adult patients with eosinophilic granulomatosis with polyangiitis (EGPA). This September, the United StatesFDAApproval of Nucala for the Treatment of Hypereosinophilic Syndrome (HES). In addition to CRSwNP, GSK is currently also evaluating the potential of Nucala in treating chronic obstructive pulmonary disease (COPD). (Bioon.com)

Original Source:FDA accepts GSK’s filing of Nucala (mepolizumab) for use in chronic rhinosinusitis with nasal polyps