Depemokimab (Exdensur): The First Twice-Yearly Anti-IL-5 Biologic for Severe Eosinophilic Asthma (September 17, 2026)
Table of Contents
A biologic you take twice a year
Depemokimab, sold as Exdensur (nonproprietary name depemokimab-ulaa, development code GSK3511294), is a monoclonal antibody for severe asthma with one defining feature: it is designed to be injected only twice a year. Most biologics for asthma are given every four or eight weeks, and keeping to that schedule is a real-world burden that many patients struggle with. GSK built depemokimab to work at a fixed 100 mg subcutaneous dose once every 26 weeks - two shots a year - making it the first 'ultra-long-acting' IL-5 biologic. The target is the same one that established anti-IL-5 antibodies already hit, but the engineering behind it is what lets a twice-yearly schedule keep the underlying inflammation suppressed.
Why interleukin-5 matters in asthma
Severe asthma is not one disease. In a large subgroup, the inflammation is 'type 2' and driven by eosinophils - white blood cells that flood the airways and fuel swelling, mucus and the recurrent flare-ups known as exacerbations. The single most important signal telling eosinophils to mature, survive and migrate into tissue is a cytokine called interleukin-5, or IL-5. Turn down IL-5 and eosinophil numbers fall, airway inflammation eases, and exacerbations become less frequent. That logic underpins a whole class of asthma biologics - mepolizumab and reslizumab, which grab IL-5 itself, and benralizumab, which targets the IL-5 receptor. Depemokimab belongs to the first group: it binds IL-5 and stops it from reaching eosinophils.
How depemokimab is engineered
Depemokimab is a humanized IgG1 monoclonal antibody, and two engineering choices give it its unusual staying power. First, it has been 'affinity matured' - refined so that it grips IL-5 far more tightly than earlier antibodies; in a cell-based assay it is roughly 29 times more potent than mepolizumab. Second, its Fc region carries a triple amino-acid substitution known as the YTE mutation (M252Y/S254T/T256E), which increases binding to the neonatal Fc receptor (FcRn). FcRn is the recycling system that rescues antibodies from being broken down, so strengthening that interaction dramatically lengthens the antibody's half-life. Combine a very tight grip on the target with an antibody that lingers far longer in the body, and you get durable IL-5 suppression from a single dose that lasts about six months.
The SWIFT-1 and SWIFT-2 trials
Depemokimab's approval rests on two replicate Phase 3 studies, SWIFT-1 (NCT04719832) and SWIFT-2 (NCT04718103), in adults and adolescents aged 12 and older with severe asthma and an eosinophilic phenotype. On top of their standard inhaled maintenance therapy, participants received either depemokimab 100 mg or placebo at week 0 and week 26 and were followed for 52 weeks, with the annualized rate of asthma exacerbations as the primary endpoint. Twice-yearly depemokimab significantly reduced exacerbations versus placebo - about a 58% reduction in SWIFT-1 and a 48% reduction in SWIFT-2. Just as important for patients and health systems, a pooled analysis found roughly a 72% reduction in the most serious exacerbations, those requiring hospitalization or an emergency-department visit. The safety profile was consistent with the anti-IL-5 class, with injection-site reactions, headache and nasopharyngitis among the more common effects.
FDA approval and how it's used
On the strength of the SWIFT results, the U.S. FDA approved Exdensur in December 2025 as an add-on maintenance treatment for severe asthma with an eosinophilic phenotype (type 2 inflammation) in patients aged 12 and older. It is given as a 100 mg subcutaneous injection once every 26 weeks. Crucially, depemokimab is a maintenance therapy, not a rescue medicine: it does not relieve an acute asthma attack or acute bronchospasm, and patients keep their reliever inhaler and other controllers. Because a dose lasts about six months, the drug also stays in the body a long time, so it cannot be quickly cleared if a problem arises - one trade-off of the convenient schedule.
Beyond asthma: nasal polyps and other eosinophilic diseases
Eosinophils and IL-5 drive more than asthma, and depemokimab is being tested across that family of conditions. It is most advanced in chronic rhinosinusitis with nasal polyps (CRSwNP), a disease of the sinuses in which eosinophilic inflammation produces obstructive polyps; the ANCHOR-1 (NCT05274750) and ANCHOR-2 (NCT05281523) trials evaluated twice-yearly depemokimab against placebo, and on the basis of that program depemokimab has been approved for CRSwNP in China. GSK and investigators are also exploring IL-5 blockade with depemokimab in other eosinophil-associated diseases such as eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome, where the same twice-yearly approach could simplify long-term treatment.
Where it fits - and what to watch
Depemokimab enters a crowded field of type 2 asthma biologics - the IL-5 agents mepolizumab, reslizumab and benralizumab, the IL-4/IL-13 blocker dupilumab, and the upstream TSLP antibody tezepelumab. Its distinguishing pitch is not a new mechanism but a new rhythm: comparable exacerbation control from only two injections a year. The open questions are the ones any long-interval therapy raises - how twice-yearly dosing performs against monthly options in head-to-head and real-world use, how it does in patients with very high eosinophil counts or overlapping conditions, and how its long-term safety looks as more people are treated for longer. For a common, burdensome disease, though, the arrival of an effective anti-IL-5 antibody that fits into a twice-a-year routine is a meaningful practical advance. This article is background information, not medical advice.
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Citations
- [1] Exdensur (depemokimab-ulaa) FDA Approval History - Drugs.com Source
- [2] FDA Approves GSK's Exdensur as Twice-Yearly Add-On Therapy for Severe Asthma - Pharmaceutical Executive Source
- [3] FDA Approves Depemokimab as Add-On Maintenance Treatment in Severe Asthma - Pharmacy Times Source
- [4] EXDENSUR (depemokimab-ulaa) injection, for subcutaneous use - FDA Prescribing Information (label) Source
- [5] Depemokimab, the first ultra-long-acting anti-IL-5 monoclonal antibody for severe eosinophilic asthma - Med (Cell Press) Source
- [6] Efficacy and Safety of Depemokimab (GSK3511294) in Participants With Chronic Rhinosinusitis With Nasal Polyps (ANCHOR-1; NCT05274750) - ClinicalTrials.gov Source
- [7] Exdensur (depemokimab) approved in China for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) - GSK Source
- [8] Depemokimab: toward biannual biologic therapy for severe eosinophilic asthma - Respiratory Research Source
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