Positive results from phase III severe asthma trials, SWIFT-1 and SWIFT-2, of depemokimab

Both SWIFT-1 and SWIFT-2 met their primary endpoints of a reduction in the annualised rate of clinically significant exacerbations (asthma attacks) over 52 weeks. Across both trials the overall incidence and severity of treatment-emergent adverse events were similar in patients treated with either depemokimab or placebo. Further analysis of these data is ongoing.

Depemokimab is the first ultra-long-acting biologic to be evaluated in phase III trials with a binding affinity and high potency for interleukin-5 (IL-5), enabling six-month dosing intervals for patients with severe asthma.IL-5 is known to be a key cytokine (protein) in type 2 inflammation. This inflammation, typically identified by elevated blood eosinophil count, is the underlying pathology responsible for more than 80% of people with severe asthma and can lead to unpredictable exacerbations.

Kaivan Khavandi, SVP, Global Head of Respiratory/Immunology R&D, said: “These results add to the established body of evidence that targeted inhibition of IL-5 plays a key role in reducing type 2 inflammation that drives severe asthma exacerbations. Depemokimab could offer the possibility of sustained inhibition of this pathway, with a dosing schedule of just two injections per year. This is important as research shows that 73% of physicians believe longer dosing intervals would be beneficial to patients who are often juggling multiple therapies.”

Expertise in respiratory diseases and the science of IL-5 has informed the ongoing evidence generation program evaluating the impact of six-month dosing of sustained IL-5 inhibition in patients achieving clinical remission in severe asthma. The full results of SWIFT-1 and SWIFT-2 will be presented at an upcoming scientific congress and will be used to support regulatory submissions to health authorities worldwide.

Depemokimab is currently not approved anywhere in the world.

About the depemokimab development programme: The phase III programme consists of SWIFT-1 and SWIFT-2 in severe asthma, along with an open label extension study (AGILE). SWIFT-1 and SWIFT-2 were replicate 52-week, randomised, double-blind, placebo-controlled, parallel-group, multi-centre phase III clinical trials. The trials assessed the efficacy and safety of depemokimab adjunctive therapy in 375 and 380 participants who were randomised to receive depemokimab or a placebo, in addition to their standard of care treatment with medium to high-dose inhaled corticosteroids plus at least one additional controller. An additional study (NIMBLE) is underway to assess the efficacy and safety of depemokimab when participants with severe asthma are switched from mepolizumab or benralizumab.

Depemokimab’s extended half-life has the potential to provide sustained inhibition of broad inflammatory functions and is being investigated in a variety of type 2 inflammatory conditions. Depemokimab is also currently being evaluated in phase III trials across a range of other IL-5 mediated diseases, including eosinophilic granulomatosis with polyangiitis (EGPA), chronic rhinosinusitis with nasal polyps (CRSwNP) and hypereosinophilic syndrome (HES).

About severe asthma and type 2 inflammation: Severe asthma is defined as asthma that requires treatment with high-dose inhaled corticosteroids plus a second controller (and/or systemic corticosteroids) or biologic therapy, to prevent it from becoming ‘uncontrolled’ or which remains ‘uncontrolled’ despite therapy. In more than 80% of patients with severe asthma, their condition is driven by type 2 inflammation in which patients exhibit elevated levels of eosinophils (a type of white blood cell). Blood eosinophils count can be measured via a simple blood test. IL-5 is a core cytokine (protein) in type 2 inflammation alongside IL-4 and IL-13.5 Type 2 inflammation drives the underlying pathology in a variety of immune-mediated conditions. IL-5 is responsible for the growth, activity and survival of eosinophils.