An international scientific team has reported the success of the third phase of clinical trials of the drug depemokimab for chronic rhinosinusitis with nasal polyps. These are monoclonal antibodies to interleukin-5, which are administered every six months. The report on the work was published in The Lancet, where an editorial is also devoted to it.
Chronic rhinosinusitis with nasal polyps (CRSNP) is a chronic inflammation that causes damage and abnormal regeneration of the mucous membranes of the nose and sinuses. This results in persistent or recurrent symptoms such as nasal congestion, rhinorrhea, facial pain or pressure, and loss of smell, as well as polyp growth. The disease is usually treated with topical glucocorticoids, sometimes in combination with surgical removal of the polyps. However, long-term use of such drugs is associated with an increased risk of side effects and is not always effective enough, and polyps often grow back after removal.
The most common cause of CRSNP (up to 85 percent of cases) is type 2 inflammation. Its mediators are certain cytokines, such as interleukins 4, 5 and 13. With this in mind, biological drugs (monoclonal antibodies) that target inflammation mechanisms have been developed and introduced as adjuvant therapy for severe forms of the disease: dupilumab (binds the alpha subunit of the interleukin 4 receptor, recently approved for use in chronic obstructive pulmonary disease), mepolizumab (binds interleukin 5) and omalizumab (binds immunoglobulin E). All of them are administered every 2-4 weeks. Depemokimab (GSK3511294) has become the first ultra-long-acting anti-interleukin 5 drug, the pharmacokinetics of which provide an effect for six months after injection. It has previously demonstrated efficacy in severe bronchial asthma in clinical trials.
Philippe Gevaert of Ghent University and colleagues, sponsored by GlaxoSmithKline, conducted the double-blind, randomized, placebo-controlled phase III trials ANCHOR-1 and ANCHOR-2 at 190 clinical centers in 16 countries. A total of 528 adult patients with decompensated CRSPC, bilateral polyps with an endoscopic score of at least five out of eight possible points, severe clinical manifestations, and a history of either systemic glucocorticoid therapy, surgery, or both.
In a randomized fashion, 272 participants were given 100 mg of depemokimab subcutaneously twice 26 weeks apart, or 256 received placebo; they were followed for 52 weeks from the first injection. All participants also received standard glucocorticoid therapy intranasally and, if needed, short courses of systemic glucocorticoids, as well as nasal saline irrigation. Subjective impressions, symptom severity assessment, endoscopy, CT, and blood samples for pharmacodynamic and immunogenicity analysis were collected at the beginning and end of the study.
By week 52 of observation, depemokimab administration in both trials resulted in significant improvements in mean endoscopic polyp and nasal obstruction scores. The incidence of adverse events did not differ statistically significantly between the treatment and control groups.
Thus, the addition of twice-yearly depemokimab injections to standard therapy improves clinically important CRS outcomes compared with placebo and is well tolerated, supporting its use for this indicator, the authors conclude.
Previously, clinical trials of the drug benralizumab, a monoclonal antibody to the alpha subunit of the interleukin-5 receptor, were conducted, which showed that it is superior to the glucocorticoid prednisolone in relieving exacerbations of bronchial asthma and chronic obstructive pulmonary disease accompanied by eosinophilia.
