The U.S. Food and Drug Administration has approved Exdensur (depemokimab-ulaa) as an add-on maintenance therapy for severe asthma with an eosinophilic phenotype in adults as well as adolescents aged ≥12 years. It is manufactured by the GSK Biopharma company. It is the first and only ultra-long-acting biologic for this population, requiring dosing just twice yearly.
Depemokimab is an interleukin-5 (IL-5) antagonist. It is a monoclonal antibody that is designed with an extended half-life, which allows the sustained suppression of type 2 inflammation. Type 2 inflammation is a key driver of disease in >80% of patients with severe asthma. In the US, around 2 million individuals have severe asthma, and about half continue to experience frequent exacerbations despite available treatments. However, biologics can improve the control of disease; only a minority of eligible patients receive them. Longer dosing intervals may improve clinical outcomes, acceptance, and adherence while reducing the burden of healthcare.
This approval was as per results data from SWIFT-1 (NCT04719832) and SWIFT-2 (NCT04718103) Phase III clinical trials. This study is multicenter, randomized, double-blind, placebo-controlled, and a parallel-group design. These studies evaluated the safety and efficacy of depemokimab as an add-on treatment in severe asthma patients. A total of 382 patients (mean age = 54±14.2 years, female = 58%) were included in the SWIFT-1 trial, and 380 patients (mean age = 53±16.2 years, female = 63%) were included in the SWIFT-2 trial. All these patients received the standard of care (SOC) with medium to high-dose inhaled corticosteroids plus at least one additional controller. In SWIFT-1, 250 patients received depemokimab plus SOC, whereas 132 received placebo plus SOC. In SWIFT-2, 252 patients received depemokimab plus SOC and 128 received placebo plus SOC. All these patients in both trials were followed for 52 weeks.
Two clinical studies demonstrated that sustained exacerbation reduction occurs with twice-yearly dosing. Over 52 weeks, depemokimab reduced annualized asthma exacerbation rates by 58% in SWIFT-1 and 48% in SWIFT-2 versus placebo with rate ratios of 0.42 (95% confidence interval [CI] = 0.30-0.59) and 0.52 (95% CI = 0.36-0.73), respectively (both p <0.001). Annualized exacerbation rates were found to be 0.46 vs 1.11 in SWIFT-1 and 0.56 vs 1.08 in SWIFT-2 for treatment vs placebo arms.
Secondary outcomes showed fewer hospitalizations or emergency department (ED)-related exacerbations with depemokimab (1-4%) compared to placebo (8-10%). A pooled analysis revealed a 72% reduction in clinically significant exacerbations requiring ED visits or hospitalization with a rate ratio of 0.28 (95% CI = 0.13-0.61) and p = 0.002. Depemokimab was well tolerated with safety parameters comparable to placebo.
EXDENSUR is recommended at a dose of 100 mg once every six months and administered as a subcutaneous injection into the abdomen, upper arm, or thigh. Common adverse reactions (≥4%) were pharyngitis, allergic rhinitis, upper respiratory tract infection, arthralgia, and influenza. Hypersensitivity reactions, including anaphylaxis, may occur and need immediate discontinuation and appropriate treatment. Inhaled or systemic corticosteroids should not be stopped abruptly and should be tapered gradually if needed. Pre-existing helminth infections must be treated before initiation of EXDENSUR therapy.
Kaivan Khavandi, senior vice president and Global head of immunology, respiratory, and inflammation R&D, GSK, said that EXDENSUR offers US physicians twice-yearly dosing to provide sustained protection against exacerbations in severe eosinophilic asthma. Depemokimab has received UK medicine and healthcare products regulatory agency (MHRA) approval, a positive committee for medicinal products for human use (CHMP) opinion in Europe, and is under regulatory review globally, including Japan and China, with an EU decision expected during Q1 2026.
Reference: GSK. Exdensur (depemokimab) was approved by the US FDA for the treatment of severe asthma. Published December 23, 2025. Accessed December 23, 2025. Exdensur (depemokimab) approved by US FDA for the treatment of severe asthma | GSK
