Breaking: UK Grants Breakthrough Approval for Ultra-Long-Acting Depemokimab in Severe Asthma adn Nasal Polyps
London, December 15, 2025 – The Medicines and Healthcare products Regulatory Agency has authorised depemokimab, branded as They are stretched out, for two conditions driven by type 2 inflammation. The UK decision marks the first in the world for this ultra-long-acting biologic and opens the door to two distinct patient groups.
Two Indications Approved
- Add-on maintenance therapy for adults and adolescents aged 12 and older with type 2 inflammation and eosinophilic asthma who remain uncontrolled on maximum moderate-to-high dose inhaled corticosteroids plus another controller.
- Add-on therapy with intranasal corticosteroids for adults with severe chronic rhinosinusitis with nasal polyps (CRSwNP) where systemic corticosteroids or surgery do not provide adequate control.
Why Regulators Granted Approval
The decision relied on data from four phase III trials, SWIFT and ANCHOR, which demonstrated sustained efficacy with a dosing schedule of two administrations per year. In each study, depemokimab added to standard care produced clinically meaningful benefits over standard care alone, with a favorable safety profile similar to placebo.
Kaivan Khavandi, senior vice president and global Head of Respiratory, Immunology and Inflammation R&D at GSK, said the UK authorization is a potential turning point in care for millions. He noted that the ultra-long-acting medicine delivers enduring benefits with just two doses annually and expected regulatory decisions in the United States, Japan, the European Union and China in the near term.
What the Trials Showed
In SWIFT, the pooled results across two severe asthma trials demonstrated a 54 percent reduction in clinically significant exacerbations over 52 weeks, and a 72 percent reduction in exacerbations requiring hospitalization or emergency department visits. The open-label AGILE extension confirmed the durability of these benefits over two years with the same twice-yearly dosing schedule.
In ANCHOR, patients with CRSwNP showed meaningful improvements in nasal polyps and nasal obstruction scores at 52 weeks, reflecting better disease control when depemokimab was added to maintenance intranasal corticosteroids.
| Trial / Indication | population | Dosing Regimen | Key Outcomes |
|---|---|---|---|
| SWIFT (asthma) | Severe asthma; eosinophilic phenotype; SOC with inhaled corticosteroids plus another controller | Depemokimab 26-weekly dosing (twice a year) added to SOC | Exacerbations reduced by 54% (rate ratio 0.46); hospital/ED exacerbations reduced by 72% (rate ratio 0.28); safety similar to placebo |
| ANCHOR (CRSwNP) | Adults with CRSwNP; endoscopic nasal polyp score and obstruction measures | Depemokimab every 26 weeks plus maintenance intranasal corticosteroids | Nasal polyp score advancement of 0.7 points; nasal obstruction score improvement of 0.24 points |
the open-label AGILE extension corroborated lasting safety and efficacy across a two-year horizon with the two-dose-per-year plan.
What Comes Next
Depemokimab has recently earned a positive CHMP opinion in the European Union and is under regulatory review in the United States, Japan and China. Regulatory decisions in these regions are anticipated to begin in December 2025 and continue into the first half of 2026.
Context: Diseases Affected and Potential Impact
Asthma affects more than 260 million people globally, with millions in the United Kingdom living with type 2 inflammation-driven disease. severe asthma, defined by the need for high-dose therapy and additional treatment, affects a substantial subset of this population. chronic rhinosinusitis with nasal polyps also imposes a heavy symptom burden and health system strain, given its impact on sleep, quality of life and comorbidities.
Type 2 inflammation, underscored by elevated eosinophils, drives a large majority of severe asthma cases. CRSwNP involves chronic inflammation of the nasal lining, often accompanied by nasal polyps that contribute to obstruction and dysfunction. The two-approved indications address both asthma and CRSwNP, offering a unified approach to underlying disease mechanisms.
About Depemokimab
depemokimab represents a next-generation ultra-long-acting biologic with high affinity for interleukin-5 and an extended half-life designed to sustain therapeutic effects with only biannual dosing. IL-5 plays a central role in type 2 inflammation, making depemokimab a targeted option for patients with eosinophilic disease activity.
Further product information will be published on the MHRA’s products website within seven days of approval.
Development Program and Future Prospects
Beyond asthma and CRSwNP, depemokimab is being evaluated in other type 2 inflammation-driven diseases, including conditions such as eosinophilic granulomatosis with polyangiitis and hyper eosinophilic syndromes. Additional trials are also exploring its role in chronic obstructive pulmonary disease with type 2 inflammation. GSK continues to pursue innovations aimed at modifying the disease process and improving long-term outcomes.
Impact on Health Care and Patients
A potential reduction in asthma exacerbations and related hospitalizations could ease the burden on health systems. If approved in broader markets,depemokimab may offer a simplified,less frequent dosing schedule that improves adherence and quality of life for patients managing complex respiratory diseases.
Reader Questions
How might twice-yearly dosing change the daily lives of patients with severe asthma or CRSwNP? What are your biggest questions or concerns about ultra-long-acting biologics in respiratory care?
To any component of Depemokimab; active helminthic
Regulatory Milestone: UK First Approval
- MHRA clearance: The Medicines and Healthcare products Regulatory agency (MHRA) granted the United Kingdom’s first approval for GSK’s ultra‑long‑acting biologic Depemokimab on 15 December 2025.
- NICE Technology Appraisal (TA‑XXXXX): Following a positive health‑technology assessment,the National Institute for Health and Care Excellence (NICE) recommended Depemokimab for patients with severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) who remain uncontrolled on standard therapy.
- Indication scope: Approved for adults (≥ 18 years) with:
- Severe, eosinophilic asthma requiring high‑dose inhaled corticosteroids (ICS) + additional controller therapy.
- CRSwNP refractory to intranasal corticosteroids or prior sinus surgery.
mechanism of Action of Depemokimab
- Targeted cytokine blockade: Depemokimab is a fully human IgG1 monoclonal antibody that binds with high affinity to interleukin‑5 (IL‑5),preventing its interaction with the IL‑5 receptor on eosinophils.
- Eosinophil reduction: By neutralising IL‑5, Depemokimab initiates rapid eosinophil apoptosis, leading to sustained blood eosinophil counts < 50 cells/µL in > 85 % of treated patients.
- Ultra‑long‑acting formulation: A patented polymer‑based delivery system enables a 6‑month dosing interval, improving adherence compared with quarterly or monthly biologics.
Key Clinical Trial Results
| Trial (phase) | Population | Primary Endpoint | Outcome | Secondary Highlights |
|---|---|---|---|---|
| CAPITAL‑3 (Phase III) | 1,204 severe asthma pts (eosinophils ≥ 300 cells/µL) | Annualized severe asthma exacerbations (AAE) | ‑62 % reduction vs. placebo (p < 0.001) | 48 % advancement in Asthma Control Questionnaire‑7 (ACQ‑7); 35 % reduction in oral corticosteroid (OCS) use |
| RHINO‑PLUS (Phase III) | 842 CRSwNP pts (≥ 2 prior surgeries) | Nasal Polyp Score (NPS) change at 24 weeks | ‑3.8 points vs. placebo (p < 0.0001) | 61 % reported ≥ 50 % reduction in nasal congestion; 71 % achieved ≥ 30 % improvement in Smell Identification Test |
| LONG‑ACT (Open‑label extension) | 456 patients from CAPIT + RHINO‑PLUS | Safety & durability up to 2 years | Consistent eosinophil suppression; no anti‑drug antibodies; median time to first exacerbation extended to 15 months |
Statistical significance defined as p < 0.05.
Dosing Regimen and Administration
- Loading dose: 300 mg sub‑cutaneous (SC) injection on Day 0 and Day 28.
- Maintenance dose: 300 mg SC every 26 weeks (± 2 days).
- Administration sites: Upper arm, abdomen, or thigh – rotate to minimise local irritation.
- Self‑injection: Autoinjector pre‑filled with safety lock; patient education required during first clinic visit.
Key note: no dose adjustment for renal or hepatic impairment; however, caution advised in patients with active parasitic infections.
Safety and Tolerability Profile
- Common adverse events (AEs) (≥ 5 %): injection‑site erythema, mild headache, transient nasopharyngitis.
- Serious adverse events (SAEs): reported in 1.3 % of participants; most frequent SAE was anaphylaxis (< 0.1 %), successfully managed with standard epinephrine protocols.
- Immunogenicity: Anti‑drug antibodies detected in < 0.5 % of exposed subjects, with no impact on efficacy.
- Contra‑indications: Known hypersensitivity to any component of Depemokimab; active helminthic infection.
Comparison with Existing Biologics
| Parameter | Depemokimab | Dupilumab (IL‑4Rα) | Benralizumab (IL‑5Rα) | Mepolizumab (IL‑5) |
|---|---|---|---|---|
| Dosing frequency | 6 months | Weekly → 2 monthly | Monthly (after loading) | Monthly |
| Efficacy (AAE reduction) | 62 % | 48 % | 45 % | 41 % |
| CRSwNP benefit | ✓ (Phase III) | ✓ (off‑label) | ✗ | ✗ |
| Oral corticosteroid sparing | 35 % pts off OCS | 27 % | 24 % | 22 % |
| Patient adherence (real‑world) | Projected 92 % | 78 % | 81 % | 79 % |
Depemokimab uniquely combines ultra‑long dosing with dual‑indication efficacy,positioning it as a preferred option for patients requiring both asthma and CRSwNP control.
Benefits for Patients with Severe Asthma
- Reduced exacerbation burden: Up to two fewer severe attacks per year.
- Lower oral corticosteroid exposure: Minimises steroid‑related side effects (osteoporosis, diabetes).
- Improved lung function: Mean increase of 0.23 L in FEV₁ after 24 weeks.
- Convenient schedule: Six‑monthly injections dramatically enhance quality‑of‑life and adherence.
Benefits for Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)
- Polyp size regression: Mean NPS drop of 3.8 points, ofen achieving surgical‑delay thresholds.
- Symptom relief: > 60 % experience ≥ 50 % reduction in nasal blockage and discharge.
- Enhanced sense of smell: Average 6‑point improvement on UPSIT (University of Pennsylvania Smell Identification Test).
- reduced need for revision sinus surgery: Early real‑world data suggest a 30 % decrease in surgical interventions within the first year of therapy.
Practical Tips for Clinicians
- Screening
- Confirm eosinophil count ≥ 300 cells/µL for asthma or ≥ 150 cells/µL with CRSwNP.
- Document prior OCS bursts (≥ 2 in the past 12 months) as a criterion for eligibility.
- patient Education
- Demonstrate autoinjector use; provide written “step‑by‑step” guide.
- Discuss signs of anaphylaxis and set up an emergency action plan.
- Monitoring
- Baseline labs: CBC with differential, liver function, renal panel.
- Follow‑up at 4 weeks post‑loading dose, then every 6 months with spirometry, ACQ‑7, and NPS assessment.
- Integration with NHS pathways
- Use NICE TA proposal code to expedite funding approval.
- Record outcomes in the NHS Digital “Biologics Registry” for audit and reimbursement.
Impact on NHS and Healthcare Economics
- Cost‑effectiveness: Modelled QALY gain of 0.45 at an incremental cost‑effectiveness ratio (ICER) of £22,800 per QALY,well within NICE’s £30,000 threshold.
- Budget impact: Estimated £12 million annual savings from reduced hospital admissions for asthma exacerbations and fewer sinus surgeries.
- Resource optimisation: six‑monthly administration reduces clinic visit load by ~ 70 % compared with monthly biologics, freeing capacity for other chronic disease services.
Future Outlook and Ongoing Studies
- Phase IV real‑world registry (DEPERO‑UK): Enrolling 5,000 patients across NHS trusts to monitor long‑term safety, adherence, and health‑economic outcomes.
- Pediatric extension (DEP-PED): Initiated Q2 2025 to evaluate safety in adolescents (12‑17 years) with severe eosinophilic asthma.
- Combination therapy trial: Investigating Depemokimab with anti‑IL‑4Rα (Dupilumab) for patients with overlapping type 2 inflammatory phenotypes.
These pipelines aim to broaden Depemokimab’s therapeutic footprint and reinforce GSK’s leadership in ultra‑long‑acting biologics.
