Twice-yearly drug eases symptoms in chronic rhinosinusitis with polyps

An international collaboration of researchers, sponsored by GSK and working on behalf of the ANCHOR-1 and ANCHOR-2 trial investigators, conducted two Phase III clinical trials to evaluate depemokimab, an ultra-long-acting anti-IL-5 biologic drug, for chronic rhinosinusitis with nasal polyps.

Results demonstrate that depemokimab significantly improves total nasal polyps score and nasal obstruction symptoms while maintaining a safety profile comparable to placebo.

Chronic rhinosinusitis with nasal polyps is characterized by persistent inflammation of the nasal and paranasal mucosa, leading to severe nasal obstruction, sinus pressure, loss of smell, and recurrent infections. Current treatments involve intranasal corticosteroids, short-term systemic corticosteroids for symptom exacerbations, and surgical removal of nasal polyps.

Type 2 inflammation is driven by multiple cytokines, including interleukin-5 (IL-5). Biologics such as mepolizumab (anti-IL-5), dupilumab (anti-IL-4Rα), and omalizumab (anti-IgE) have been effective in reducing symptoms and inflammation but require frequent dosing intervals of two to four weeks.

Depemokimab is an ultra-long-acting anti-IL-5 biologic engineered with enhanced IL-5 binding affinity, increased potency, and an extended half-life, enabling sustained IL-5 inhibition and twice-yearly administration.

Previous Phase I and III studies in severe asthma demonstrated its ability to sustain IL-5 inhibition and reduce blood eosinophil counts for extended periods. ANCHOR-1 and ANCHOR-2 are the first large-scale trials evaluating depemokimab in patients with chronic rhinosinusitis with nasal polyps.

In the study, “Efficacy and Safety of Twice-Yearly Depemokimab in Chronic Rhinosinusitis with Nasal Polyps (ANCHOR-1 and ANCHOR-2),” published in The Lancet, researchers conducted randomized, double-blind, placebo-controlled, parallel-group trials to assess the efficacy and safety of 100 mg subcutaneous depemokimab administered every 26 weeks.

A total of 540 individuals were enrolled, with 528 included in the final analysis across 190 clinical sites in 16 countries, including Argentina, Belgium, Canada, China, France, Germany, Italy, Japan, the Netherlands, Poland, Romania, Spain, Sweden, Türkiye, the United Kingdom, and the United States.

Participants were 18 years or older, had inadequately controlled chronic rhinosinusitis with nasal polyps, and had either previous surgery or prior systemic corticosteroid use. Participants were randomly assigned 1:1 to receive either depemokimab or placebo, in addition to standard-of-care treatment.

Among the 528 patients who completed the study, depemokimab demonstrated statistically significant improvements over placebo in the coprimary endpoints. Nasal polyps score (0–8 scale) at week 52 improved with a treatment difference of -0.7 (95% CI -0.9 to -0.4). Nasal obstruction verbal response scale score (0–3 scale) improved with a treatment difference of -0.24 (95% CI -0.39 to -0.08).

Secondary endpoints included reductions in rhinorrhea severity, Lund-Mackay CT scores, SNOT-22 scores, and systemic corticosteroid use. While trends favored depemokimab across all secondary endpoints, not all reached statistical significance in individual trials.

Integrated analysis confirmed a significant reduction in SNOT-22 scores (-8.1, 95% CI -13.9 to -2.3). The observed 27% reduction in surgery risk (HR 0.735, 95% CI 0.495 to 1.092, p=0.128) did not achieve statistical significance.

Depemokimab was well tolerated, with similar rates of adverse events between treatment and placebo groups. Treatment discontinuation due to adverse events occurred in less than 1% of participants. No deaths were reported.

Depemokimab demonstrated statistically significant reductions in nasal polyps and obstruction symptoms in patients with severe, uncontrolled chronic rhinosinusitis with nasal polyps.

While its efficacy aligns with existing biologics, the reduced dosing schedule of twice-yearly administration offers a less burdensome alternative, potentially improving adherence and quality of life. Results support depemokimab as a viable long-term treatment option for chronic rhinosinusitis with nasal polyps.

© 2025 Science X Network

An international collaboration of researchers, sponsored by GSK and working on behalf of the ANCHOR-1 and ANCHOR-2 trial investigators, conducted two Phase III clinical trials to evaluate depemokimab, an ultra-long-acting anti-IL-5 biologic drug, for chronic rhinosinusitis with nasal polyps.

Results demonstrate that depemokimab significantly improves total nasal polyps score and nasal obstruction symptoms while maintaining a safety profile comparable to placebo.

Chronic rhinosinusitis with nasal polyps is characterized by persistent inflammation of the nasal and paranasal mucosa, leading to severe nasal obstruction, sinus pressure, loss of smell, and recurrent infections. Current treatments involve intranasal corticosteroids, short-term systemic corticosteroids for symptom exacerbations, and surgical removal of nasal polyps.

Type 2 inflammation is driven by multiple cytokines, including interleukin-5 (IL-5). Biologics such as mepolizumab (anti-IL-5), dupilumab (anti-IL-4Rα), and omalizumab (anti-IgE) have been effective in reducing symptoms and inflammation but require frequent dosing intervals of two to four weeks.

Depemokimab is an ultra-long-acting anti-IL-5 biologic engineered with enhanced IL-5 binding affinity, increased potency, and an extended half-life, enabling sustained IL-5 inhibition and twice-yearly administration.

Previous Phase I and III studies in severe asthma demonstrated its ability to sustain IL-5 inhibition and reduce blood eosinophil counts for extended periods. ANCHOR-1 and ANCHOR-2 are the first large-scale trials evaluating depemokimab in patients with chronic rhinosinusitis with nasal polyps.

In the study, “Efficacy and Safety of Twice-Yearly Depemokimab in Chronic Rhinosinusitis with Nasal Polyps (ANCHOR-1 and ANCHOR-2),” published in The Lancet, researchers conducted randomized, double-blind, placebo-controlled, parallel-group trials to assess the efficacy and safety of 100 mg subcutaneous depemokimab administered every 26 weeks.

A total of 540 individuals were enrolled, with 528 included in the final analysis across 190 clinical sites in 16 countries, including Argentina, Belgium, Canada, China, France, Germany, Italy, Japan, the Netherlands, Poland, Romania, Spain, Sweden, Türkiye, the United Kingdom, and the United States.

Participants were 18 years or older, had inadequately controlled chronic rhinosinusitis with nasal polyps, and had either previous surgery or prior systemic corticosteroid use. Participants were randomly assigned 1:1 to receive either depemokimab or placebo, in addition to standard-of-care treatment.

Among the 528 patients who completed the study, depemokimab demonstrated statistically significant improvements over placebo in the coprimary endpoints. Nasal polyps score (0–8 scale) at week 52 improved with a treatment difference of -0.7 (95% CI -0.9 to -0.4). Nasal obstruction verbal response scale score (0–3 scale) improved with a treatment difference of -0.24 (95% CI -0.39 to -0.08).

Secondary endpoints included reductions in rhinorrhea severity, Lund-Mackay CT scores, SNOT-22 scores, and systemic corticosteroid use. While trends favored depemokimab across all secondary endpoints, not all reached statistical significance in individual trials.

Integrated analysis confirmed a significant reduction in SNOT-22 scores (-8.1, 95% CI -13.9 to -2.3). The observed 27% reduction in surgery risk (HR 0.735, 95% CI 0.495 to 1.092, p=0.128) did not achieve statistical significance.

Depemokimab was well tolerated, with similar rates of adverse events between treatment and placebo groups. Treatment discontinuation due to adverse events occurred in less than 1% of participants. No deaths were reported.

Depemokimab demonstrated statistically significant reductions in nasal polyps and obstruction symptoms in patients with severe, uncontrolled chronic rhinosinusitis with nasal polyps.

While its efficacy aligns with existing biologics, the reduced dosing schedule of twice-yearly administration offers a less burdensome alternative, potentially improving adherence and quality of life. Results support depemokimab as a viable long-term treatment option for chronic rhinosinusitis with nasal polyps.

© 2025 Science X Network