Recently, the FDA approved GSK Company [Mepolizumab] as an add-on therapy for chronic sinusitis and nasal polyps (CRSwNP) in adults aged 18 years and older who do not respond to nasal corticosteroids to target eosinophil inflammation. This is the fourth indication of the drug in the United States for the treatment of eosinophil-driven diseases; it is also the first IL-5 monoclonal antibody approved by the FDA for this indication.

CRSwNP is a chronic disease that often occurs at the same time as other respiratory diseases, and is associated with increased levels of white blood cells called eosinophils. CRSwNP severely impairs the quality of life of patients and can cause chronic symptoms such as long-term nasal congestion, loss of smell, breathing and sleep difficulties, facial pressure, and runny nose. The incidence of the disease accounts for 2 to 4% of the U.S. population and affects more than 5 million people.

Mepolizumab is a monoclonal antibody that targets interleukin 5 (IL-5). It reduces blood eosinophils and maintains them by preventing IL-5 from binding to receptors on the surface of eosinophils. Works at a normal level.

Mepolizumab was first approved by the FDA in November 2015 for the treatment of severe eosinophilic asthma (SEA) aged 6 years and older under the trade name Nucala. It was subsequently approved by the FDA for the treatment of adult eosinophilic granulomatous polyangiitis (EGPA) and the treatment of patients with eosinophilia syndrome (HES) aged 12 years and older. In 2020, Nucala sales will be 994 million pounds.

The FDA is based on data from the key study SYNAPSE, which explored the effects of mepolizumab and placebo on more than 400 CRSwNP patients. All patients in the study received standard treatment: a previous history of surgery (approximately one-third of patients had ≥3 surgeries), and they needed further surgery due to severe symptoms and enlarged polyps.

The SYNAPSE study showed that the proportion of patients undergoing surgery was reduced by 57% in the mepolizumab group compared with the placebo group, with HR=0.43 (95% CI 0.25, 0.76). In addition, patients who received mepolizumab required systemic corticosteroid use during the 52-week treatment period. And mepolizumab has made significant improvements in reducing the size of nasal polyps and nasal congestion.

IL-5 is one of the cytokines on the Th2 pathway, which also secretes IL-4, IL-5, IL-13, IL-31 and other cytokines and stimulates type 2 immunity. Excessive activation of Th2 pathway can lead to the occurrence of severe allergic diseases, including food allergy, chronic sinusitis with nasal polyps, itching, atopic dermatitis, idiopathic urticaria, eosinophilic esophagitis, asthma, etc. Currently, the Th2 pathway target antibodies that have been approved worldwide are: mepolizumab, relizumab, benralizumab, duplizumab and omalizumab.

Among them, Mepolizumab and Relizumab are only two IL-5 monoclonal antibodies approved for marketing in the world. GSK submitted a marketing application for mepolizumab injection to the National Medical Products Administration (NMPA) in July 2020. Domestically, 3SBio's IL-5 monoclonal antibody is in the phase I clinical stage, and Mabo Pharmaceutical and Chia Tai Tianqing's mepolizumab biosimilars are in the preclinical stage.