The Medicines and Healthcare products Regulatory Agency (MHRA) has approved depemokimab (Exdensur, GSK plc) as add-on therapy for severe asthma and for chronic rhinosinusitis with nasal polyps (CRSwNP), introducing the first twice-yearly biologic option for these indications in the UK.

Depemokimab is approved as a 6-monthly subcutaneous injection. It is indicated for adults and adolescents aged 12 years or older with severe asthma, and for adults with CRSwNP whose symptoms remain inadequately controlled despite standard care and, where applicable, surgery. 

Targeting Type 2 Inflammation

Asthma inflames and narrows lung airways, making breathing difficult. Severe chronic rhinosinusitis causes inflammation of the nose and paranasal sinuses with symptoms persisting for more than 12 weeks, often leading to nasal polyps.

Julian Beach, interim executive director of healthcare quality and access at the MHRA, noted that these conditions affect a significant number of people across the UK and can be difficult to manage despite existing treatments. 

Depemokimab blocks interleukin (IL)-5, a key mediator of type 2 inflammation that drives eosinophilic disease in both asthma and CRSwNP. By reducing IL‑5 activity, the drug helps lower eosinophilic inflammation linked to airway narrowing and persistent sinonasal inflammation and polyp growth. 

The approved regimen is 100 mg administered subcutaneously every 26 weeks as add‑on treatment to existing therapy.

Reducing Exacerbations and Polyp Size

The ANCHOR-1 and ANCHOR-2 phase 3 trials evaluated depemokimab in 528 patients with inadequately controlled CRSwNP. Participants had previous surgery or prior treatment with, or intolerance to, systemic corticosteroids. 

Patients received either depemokimab (100 mg subcutaneously) or placebo every 26 weeks (with standard of care). 

Depemokimab significantly reduced total nasal polyps scores and mean nasal obstruction scores vs placebo. The treatment difference for total nasal polyp score was -0.7 in ANCHOR-1 and -0.6 in ANCHOR-2. For nasal obstruction, treatment differences were -0.23 and -0.25, respectively. 

Adverse event rates were similar between the depemokimab and placebo groups.

In severe asthma with an eosinophilic phenotype, the SWIFT-1 and SWIFT-2 phase 3 trials enrolled 762 patients with high eosinophil counts and a history of exacerbations despite medium- or high-dose inhaled glucocorticoids. Patients received either subcutaneous depemokimab 100 mg or placebo at weeks 0 and 26, plus standard care.

Annualised exacerbation rates were reduced to 0.46 in SWIFT-1 and 0.56 in SWIFT-2 with depemokimab, compared with 1.11 and 1.08, respectively, with placebo.

Safety Profile

The most common side effects, which may affect more than 1 in 10 people, include itchy skin, headache, tiredness, and injection-site reactions.

A full list of side effects will be published in the Summary of Product Characteristics and Patient Information Leaflets on the MHRA website within 7 days of approval.