Approximately 74% of patients with chronic rhinosinusitis with nasal polyps receiving depemokimab across 2 trials did not need additional intervention.
Research findings published in the Journal of Allergy and Clinical Immunology demonstrate that 2 doses of depemokimab (GSK) could achieve sufficient concentrations, effectively suppressing blood eosinophil counts in adults with inadequately controlled chronic rhinosinusitis with nasal polyps (CRSWNP) over a 52-week duration. Depemokimab had anti-IL-5 biological effects and an impact on type 2 inflammation, supporting its potential as a treatment option in patients with CRSWNP.1
CRSWNP is caused by inflammation of the nasal lining that can lead to soft tissue growths, known as nasal polyps. Symptoms such as nasal obstruction, loss of smell, facial pain, sleep disturbance, infections, and nasal discharge that can significantly affect patients’ emotional and physical well-being are common. IL-5 is a key cytokine in type 2 inflammation and is present in up to 85% of people with the disease. IL-5 is often found in high concentrations in the sinus and nasal polyp tissue of patients with CRSWNP and is usually associated with more severe disease.2
Depemokimab is a monoclonal antibody that is engineered with enhanced IL-5 binding affinity, high potency, and an extended half-life, allowing it to be administered twice per year. It is the first ultra-long-acting biologic to be evaluated in phase 3 trials of patients with CRSWNP. The phase 3 program includes the evaluation of depemokimab in other IL-5-mediated diseases, such as severe asthma, eosinophilic granulomatosis with polyangiitis, and hypereosinophilic syndrome.1,2
Depemokimab’s efficacy and safety were evaluated in the 2 randomized, double-blind, parallel group, phase 3 clinical trials, ANCHOR-1 (NCT05274750) and ANCHOR-2 (NCT05281523), which enrolled adults with inadequately controlled CRSWNP who had previous nasal polyp surgery or treatment with or intolerance to systemic corticosteroids.1,3,4 Patients were randomly assigned to receive either 100 mg of depemokimab subcutaneously or placebo every 26 weeks over a 52-week duration.
Depemokimab plasma concentrations were summarized, and blood eosinophil counts were log transformed, with ratio to baseline being analyzed. The results from these studies were presented in a late-breaking oral abstract session at the 2025 American Academy of Allergy, Asthma and Immunology (AAAAI)/World Allergy Organization (WAO) Joint Congress in San Diego, California.1,2
ANCHOR-1
ANCHOR-2
The analyses included a total of 272 patients. At the first assessment 4 weeks post-administration, the mean concentration of depemokimab was about 10.65 μg/mL. Additionally, concentrations were at their lowest at weeks 26 (pre-dose; 1.02 [0.408] μg/mL) and 52 (1.25 [0.719] μg/mL). Baseline geometric means blood eosinophil counts were 344 cells/μL and 322 cells/μL for depemokimab and placebo, respectively. At week 4, the blood eosinophil count ratio to baseline for depemokimab was about 0.104 (95% CI: 0.091, 0.118; p < .001). Further, relative reductions were sustained throughout both dosing intervals (week 26: 0.168 [95% CI: 0.148,0.191], p < .001; week 52: 0.153 [95% CI: 0.133,0.176], p < .001). These findings were consistent across both ANCHOR trials.1,3,4
Further, by week 52 in the pooled ANCHOR studies, about 74% (n = 200) of patients in the depemokimab arm and 64% (n = 164) patients in the placebo arm did not have intervention with standard of care, surgery, or disease-modulating medication (OR: 0.58 [95% CI: 0.40, 0.86], nominal p = .006). The results still trended in depemokimab’s favor even after considering intervention with surgery or disease-modulating medication alone, with about 88% (n = 239) of depemokimab-treated patients not having surgery or disease-modulating medication compared with 83% (n = 213) in the placebo group (HR: 0.713 [95% CI: 0.453, 1.124], p = .146).2
“[These] data build on the body of evidence supporting depemokimab as an ultra-long-acting treatment and demonstrate significant reductions in nasal polyps with a twice-yearly dosing regimen. With nearly 40% of patients needing repeat surgeries and many requiring long-term systemic corticosteroids, there is a clear medical need for alternative treatment options to provide sustained symptom improvement and help alleviate the debilitating burden of this disease,” Kaivan Khavandi, SVP and global head, respiratory, immunology/inflammation R&D, said in a news release.2
