Targeted therapy for eosinophilic disease! The European Union approves glaxoSmithKline for 3 new indications

-- GlaxoSmithKline (GSK) recently announced that the European Commission (EC) has approved the anti-inflammatory drug Nucala (mepolizumab), a monoclonal antibody specifically targeted to inhibit interleukin 5 (IL-5) for the treatment of 3 eosinophil-driven diseases: hypereosinophil syndrome (HES), chronic rhino-sinusitis with nasal polyposis (CRSwNP), eosinophilic granulomatosis polyangiitis (EGPA).

In the European Union, Nucala has previously been approved as an add-on therapy for the treatment of patients aged 6 years and older with severe eosinophilic asthma (SEA). It is worth mentioning that Nucala is the only therapy approved in Europe for the treatment of 4 eosinophil-driving diseases, the first anti-IL-5 biological therapy for the treatment of HES and CRSwNP, and the first targeted therapy for the treatment of EGPA.

In the United States, Nucala has been approved for treatment for 4 indications: SEA, EPGA, HES, CRSwNP. Eosinophil-driven diseases such as SEA, HES, CRSwNP, and EGPA are inflammatory diseases characterized by elevated eosinophil levels. Both HES and EGPA are rare diseases that can be life-threatening, and current patients have limited treatment options. CRSwNP can cause chronic symptoms such as nasal congestion and runny nose, and patients with severe medical conditions may require surgery, but polyps may recur, which means that patients undergo repeated surgeries, and the surgical outcome will gradually become less effective and the risk will be greater.

By reducing eosinophils in the blood to normal levels through targeted therapy, Nucala has shown therapeutic benefits in a range of eosinophil-driven diseases.

The EU approval, based on data from a series of key Phase 3 studies investigating the role of Nucala-targeted inhibition of IL-5 in the treatment of eosinophil-driven disease, showed that: (1) in patients with HES, during the 32-week study period, during the combined standard care, Nucala treated patients with HES episodes (worsening symptoms or eosinophil levels exceeding the threshold requiring escalation of treatment) were significantly reduced compared with placebo. (2) In patients with CRSwNP who underwent at least one surgery, nucala showed significant improvements in nasal polyp size at the end of the 52-week study and nasal congestion at weeks 49-52 compared with placebo, while also reducing the need for further surgery up to week 52 of the study. (3) In patients with EGPA, when combined with standard care, Nucala increased the cumulative response time and the proportion of patients who achieved remission compared with placebo.

Nucala's active pharmaceutical ingredient 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 important signals for eosinophils to migrate from the bone marrow to the lungs and other organs. Nucala binds to human IL-5, blocking the binding of IL-5 to eosinophil surface receptors. Inhibiting the binding effect of IL-5 on receptors in this way can reduce eosinophil levels in blood, tissues, sputum, which in turn can reduce eosinophil-mediated inflammation.

Based on the above mechanism of action, Nucala is being developed for a variety of diseases caused by inflammation caused by eosinophils. The drug has been evaluated in 41 clinical trials, in more than 4,000 patients, across a wide range of eosinophil indications. Currently, GSK is also evaluating Nucala's potential for the treatment of chronic obstructive pulmonary disease (COPD).

Approved in late 2015, Nucala is the first biologic therapy to target IL-5 on the market worldwide. To date, Nucala has been approved in the United States, Europe, and more than 25 other markets as an add-on maintenance therapy for patients with severe eosinophilic asthma (SEA). In the United States and the European Union, Nucala is also approved for the treatment of PEDIATRIC PATIENTS WITH SEA AGED 6-17 YEARS. In addition, nucala has also been approved as an add-on maintenance therapy for adult patients with eosinophilic granulomatous polyangiitis (EGPA) in several markets, including the United States, Japan, and Canada. In the United States, Nucala was also approved in September 2020 for the treatment of heS lasting ≥6 months, unidentified non-hematologic secondary causes, adults aged ≥ 12 years, and pediatric HES patients.

In July 2021, Nucala was approved in the United States as the first anti-IL-5 therapy to be used to treat CRSwNP for add-on maintenance of CRSwNP in adults aged 18 years and older who respond inadequately to intranasal corticosteroids (INCs).