D2.449 - Patients with Inadequately Controlled CRSwNP and Blood Eosinophil Count ≥150 cells/µL Experience Benefit with Depemokimab: An Analysis of Data from the Integrated ANCHOR-1/-2 Studies

EPOS/EUFOREA guidelines recommend that patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP), despite prior endoscopic sinus surgery, who have evidence of type 2 (T2) inflammation (indicated by blood eosinophil count [BEC] ≥150 cells/µl, among other criteria) may be considered for biologic therapy. Depemokimab is the first ultra-long-acting biologic with enhanced interleukin-5 binding affinity, high potency and an extended half-life, enabling sustained suppression of T2 inflammation and twice-yearly dosing in patients with CRSwNP. Depemokimab (100 mg administered subcutaneously every 26 weeks) was associated with early and sustained efficacy in patients with inadequately controlled CRSwNP in the Phase III ANCHOR-1/-2 trials. This analysis assessed the impact of depemokimab stratified by baseline BEC in the integrated ANCHOR-1/-2 trials. 

Adult patients were randomised to depemokimab or placebo every 26 weeks plus standard of care for 52 weeks. Key outcomes (including coprimary outcomes of change from baseline in total endoscopic nasal polyps score [NPS] at Week 52 on a 0–8 scale and mean nasal obstruction [NO] verbal response scale [VRS] score on a 0–3 scale over Weeks 49–52) were assessed based on baseline BEC subgroups (≥150/<150 cells/µL [post hoc analysis]; ≥300/<300 cells/µL [prespecified analysis]). 

Results: The integrated full analysis set comprised 528 patients. The BEC ≥150 cells/µL subgroup showed improvements with depemokimab versus placebo in NPS and NO VRS score (Table). The BEC <150 cells/µL subgroup showed similar improvements to those seen in the BEC ≥150 cells/µL subgroup with depemokimab versus placebo in NO VRS score but less pronounced efficacy with depemokimab versus placebo in NPS (Table). Improvements were shown in the BEC ≥300 cells/µL subgroup with depemokimab versus placebo in NPS and NO VRS score (Table). The BEC <300 cells/µL subgroup also showed improvement with depemokimab versus placebo in NPS and NO VRS score (Table). Improvements were similar in the BEC ≥150 and ≥300 cells/µL subgroups for both coprimary outcomes at Week 52/over Weeks 49–52 (Table). 

Twice-yearly depemokimab improved key outcomes for patients with BEC ≥150 cells/µL and ≥300 cells/µL to a similar extent in the integrated ANCHOR-1/-2 analyses, supporting the updated EPOS/EUFOREA guidance to select biologic candidates using T2 inflammation thresholds.

Funding: GSK (217095/218079; NCT05281523/NCT05274750)