GSK’s Nucala (Mepolizumab) Under EU Review for Three New Eosinophil-Driven Disease Indications

October 30, 2020 /BioValleyBIOON/ ---GlaxoSmithKline(GSK) recently announced that the European Medicines Agency (EMA) has accepted the Marketing Authorization Application (MAA) for the anti-inflammatory drug Nucala (mepolizumab) for three new indications: Hypereosinophilic Syndrome (HES), Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), and Eosinophilic Granulomatosis with Polyangiitis (EGPA).

In the European Union, Nucala has previously been approved as an add-on therapy for the treatment of severe eosinophilicAsthma(SEA) patients. If the aforementioned MAA is approved, Nucala will become the only therapy in Europe indicated for the treatment of four eosinophil-driven diseases, as well as the first biologic therapy for the treatment of HES and the first therapy for the treatment of EGPA.

In the United States, Nucala has been approved for three indications: SEA, EGPA, and HES. Eosinophil-driven diseases, such as SEA, HES, CRSwNP, and EGPA, are inflammatory conditions characterized by elevated eosinophil levels. Both HES and EGPA are rare, potentially life-threatening diseases with limited treatment options currently available for patients. CRSwNP can cause chronic symptoms, such as nasal congestion and rhinorrhea. Patients with severe disease may require surgical intervention; however, polyps may recur, necessitating repeated surgeries. Over time, the efficacy of surgery tends to diminish, while the associated risks increase.

Targeted therapy to reduce blood eosinophil levels to normal has demonstrated therapeutic benefits in a range of eosinophil-driven diseases. These three Marketing Authorization Applications (MAAs) are based on the results of a series of pivotal studies, which showed that: (1) In patients with Hypereosinophilic Syndrome (HES), during the 32-week study period, Nucala treatment, when combined with standard of care, significantly reduced HES flares (worsening of symptoms or eosinophil levels exceeding the threshold requiring treatment escalation) compared with placebo. (2)In patients with CRSwNP who had undergone at least one surgery, Nucala, when added to standard of care, demonstrated significant improvements in nasal polyp size at the end of the 52-week study and in nasal congestion during weeks 49–52, compared with placebo, while also reducing the need for further surgery through week 52 of the study. (3)In patients with EGPA, when added to standard of care, Nucala increased the cumulative time in remission and the proportion of patients achieving remission compared with placebo.

The active pharmaceutical ingredient of 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 the migration of eosinophils 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 the binding of IL-5 to its receptors in this manner, 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 26Clinical Trial, evaluated in over 3,000 patients across multiple eosinophilic indications. Currently, GSK is also evaluating the potential of Nucala for the treatment of chronic obstructive pulmonary disease (COPD).

Nucala was approved in late 2015 as the first IL-5-targeted biologic therapy launched globally. To date, Nucala has been approved in the United States, Europe, and more than 20 other markets as an add-on maintenance treatment for severe eosinophilicAsthma(SEA) patients. In the United States and the European Union, Nucala is also approved for the treatment of pediatric SEA patients aged 6 to 17 years. Furthermore, in multiple markets including the United States, Japan, and Canada, Nucala has been approved as an add-on maintenance therapy for adult patients with eosinophilic granulomatosis with polyangiitis (EGPA). In the United States, Nucala was also approved this September for the treatment of adult and pediatric patients aged ≥12 years with hypereosinophilic syndrome (HES) lasting ≥6 months and without identifiable non-hematologic secondary causes. (Bioon.com)

Original Source: GSK Nucala (mepolizumab) filings accepted by European Medicines Agency for three additional eosinophil-driven diseases