Depemokimab Shows Significant Improvement

Depemokimab is an investigational, ultra-long-acting monoclonal antibody targeting interleukin-5 (IL-5), a key cytokine (protein) in type 2 inflammation that presents in up to 85% of people with CRSwNP. Results from these studies were presented in a late-breaking oral abstract session at the 2025 AAAAI/WAO Joint Congress in San Diego, California and simultaneously published in The Lancet.

ANCHOR-1 (N=271) and ANCHOR-2 (N=257) met their co-primary endpoints, with twice-yearly administration of depemokimab showing clinically meaningful and statistically significant improvements in nasal polyp size and nasal obstruction, two key clinical measures of disease severity, versus placebo. Additionally, a pooled analysis of the two trials showed improvements (reductions) from baseline versus placebo measured by:

• Nasal polyp score (NPS, 0-8) at 52 weeks (treatment difference [95% CI], -0.7 [-0.9, -0.4], nominal p<0.001).
• Mean nasal obstruction scores (verbal response scale [VRS, 0-3]) over weeks 49-52 (treatment difference [95% CI], -0.24 [-0.39, -0.08], nominal p=0.003).
• ANCHOR-1 and ANCHOR-2 recruited a broad patient population with heterogenous symptom severity, reflective of real-world clinical practice. The treatment benefits were observed by the first assessment and sustained to week 52.
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• Kaivan Khavandi, SVP and Global Head, Respiratory, Immunology/Inflammation R&D, said: “The 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.”

In pooled analyses of the secondary endpoints from both studies, nominally significant improvements in favour of depemokimab versus placebo were observed. These include changes from baseline in rhinorrhoea VRS score, loss of smell VRS score, in addition to the Lund-Mackay CT score, a sinus imaging assessment, and SNOT-22, a disease-related quality of life measure.

By week 52 in the pooled ANCHOR studies, 74% (n=200) of patients in the depemokimab arm and 64% (n=164) patients in the placebo arm did not have intervention with SCS, surgery, or disease modulating medication (odds ratio [95% CI]: 0.58 [0.40, 0.86], nominal p=0.006). When considering intervention with surgery or disease modulating medication alone, the results still trended in depemokimab’s favour with 88% (n=239) of depemokimab-treated patients not having surgery or disease modulating medication vs. 83% (n=213) in the placebo group (hazard ratio [95% CI]: 0.713 [0.453, 1.124], p=0.146).

The proportion of patients who experienced adverse events (AEs) was similar between the depemokimab and placebo groups in ANCHOR-1 (74% [n=106] versus 79% [n=101]) and ANCHOR-2 (76% [n=98] versus 80% [n=102]). These are consistent with results from SWIFT-1 and SWIFT-2, the phase III trials of depemokimab in patients with asthma with type 2 inflammation. Additionally, <1% of patients (n=2) receiving depemokimab and 1% (n=3) on placebo, across both ANCHOR-1 and -2, discontinued treatment or withdrew from the study due to AEs. No serious adverse events were considered related to study treatment by investigators.

See citation- Gevaert P, Desrosiers M, Cornet et al. Efficacy and safety of twice per year depemokimab in chronic rhinosinusitis with nasal polyps (ANCHOR-1 and ANCHOR-2): phase 3, randomised, double-blind, parallel trials.   Lancet 2025 Feb 28:S0140-6736(25)00197-7. doi: 10.1016/S0140-6736(25)00197-7 Online ahead of print.