European Commission Approves Exdensur for Severe Asthma and Chronic Rhinosinusitis

The European Commission has approved Exdensur (depemokimab) for two indications: add-on maintenance treatment for severe asthma with type 2 inflammation and add-on therapy for chronic rhinosinusitis with nasal polyps. Exdensur is the first and only ultra-long-acting biologic in the EU to treat respiratory diseases.

The decision covers add-on maintenance treatment for severe asthma with type 2 inflammation characterised by blood eosinophil count in adults and adolescents 12 years and older who are inadequately controlled despite high dose inhaled corticosteroids plus another asthma controller. The approval also includes add-on therapy with intranasal corticosteroids for the treatment of adult patients with severe chronic rhinosinusitis with nasal polyps for whom therapy with systemic corticosteroids and/or surgery do not provide adequate disease control.

The approval is based on data from the SWIFT and ANCHOR phase 3 trials, which showed sustained efficacy with a twice-yearly dosing regimen for depemokimab. Each of the four trials met their primary or co-primary endpoints with statistically significant and clinically meaningful results, comparing the addition of depemokimab to standard of care versus standard of care alone.

In the SWIFT phase 3 trials, treatment with depemokimab resulted in a significant 58% and 48% reduction in the rate of annualised asthma exacerbations over 52 weeks from SWIFT-1 and SWIFT-2, respectively. The rate ratio (95% confidence interval) p-value was: SWIFT-1 0.42 (0.30, 0.59) p<0.001 and SWIFT-2 0.52 (0.36, 0.73) p<0.001. The annualised exacerbation rate for depemokimab versus placebo was: SWIFT-1 0.46 vs. 1.11 and SWIFT-2 0.56 vs. 1.08 exacerbations per year.

In a secondary endpoint from SWIFT-1 and SWIFT-2, patients treated with depemokimab experienced numerically fewer exacerbations requiring hospitalisation and/or emergency department visits (1% and 4%) compared with placebo (8% and 10%), respectively. A pre-specified pooled analysis of the two trials showed there was a 72% reduction in the annualised rate of clinically significant exacerbations requiring hospitalisation and/or emergency department visits over 52 weeks for depemokimab compared with placebo. The rate ratio was 0.28, 95% CI (0.13, 0.61), nominal p=0.002, with annualised exacerbation rate for depemokimab 0.02 versus placebo 0.09. The full results from the SWIFT trials were presented at the 2024 European Respiratory Society International Conference and published in the New England Journal of Medicine.

Asthma affects more than 42 million people in Europe. About 5-10% of patients experience severe asthma with many continuing to experience exacerbations and reduced quality of life despite treatment. An estimated 3 million people live with severe asthma in Europe. In addition, patients with chronic rhinosinusitis with nasal polyps face debilitating daily symptoms and almost half remain uncontrolled.

Exdensur is a novel therapy that combines high interleukin-5 binding affinity and high potency with an extended half-life, enabling the sustained suppression of disease-driving type 2 inflammation with twice-yearly dosing that could address the continued unmet need in these diseases.